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Journal Cover Journal of Pharmaceutical Sciences
  [SJR: 0.984]   [H-I: 130]   [160 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0022-3549 - ISSN (Online) 1520-6017
   Published by Elsevier Homepage  [3043 journals]
  • Editorial Advisory Board
    • Citation: Journal of Pharmaceutical Sciences 106, 10 (2017)
      PubDate: 2017-10
      DOI: 10.1016/S0022-3549(17)30578-6
      Issue No: Vol. 106, No. 10 (2017)
       
  • DHA and pGPMA Dual Modified pH Sensitive Polymeric Micelles for Target
           Treatment of Liver Cancer
    • Authors: Haojun Ma
      Abstract: In clinical therapy, the poor prognosis of hepatocellular carcinoma (HCC) is mainly attributed to the failure of chemotherapeutical agents to accumulate in tumor as well as lack of potency of tumor penetration. In this work, we developed actively tumor-targeting micelles with pH-sensitive linker as a novel nanocarrier for HCC therapy. These micelles comprised of biodegradable PEG-pAsp polymers, in which PTX can be covalently conjugated to pAsp via an acid-labile acetal bond to form pH-responsive structures.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-09
      DOI: 10.1016/j.xphs.2017.09.011
       
  • Development of a Modified Release Formulation of Lovastatin Targeted to
           Intestinal Methanogens Implicated in Irritable Bowel Syndrome with
           Constipation
    • Authors: Steven Hubert; Alan Chadwick, Vince Wacher, Olivia Coughlin, John Kokai-Kun, Andrew Bristol
      Abstract: There is growing evidence that methane production, predominantly by Methanobrevibacter smithii (M. smithii), in the intestines is a cause of constipation, pain and bloating in irritable bowel syndrome with constipation (IBS-C). M. smithii resides primarily in the large intestine but can also colonize the small intestine. In-vitro studies found that the prodrug lactone form of lovastatin, found in cholesterol lowering drugs, inhibited methane production in stool samples from patients with IBS-C. However, the cholesterol-lowering lovastatin β-hydroxyacid (HA) was ineffective at inhibiting methane production in this system.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.028
       
  • Mechanistic PBPK Modeling of the Dissolution and Food Effect of a BCS IV
           Compound – the Venetoclax Story
    • Authors: Arian Emami Riedmaier; David J. Lindley, Jeffrey A. Hall, Steven Castleberry, Russell T. Slade, Patricia Stuart, Robert A. Carr, Thomas B. Borchardt, Daniel A.J. Bow, Marjoleen Nijsen
      Abstract: Venetoclax, a selective B-cell lymphoma-2 inhibitor, is a biopharmaceutics classification system (BCS) class IV compound. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model to mechanistically describe absorption and disposition of an amorphous solid dispersion (ASD) formulation of venetoclax in humans.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.027
       
  • Enhanced Dissolution of a Porous Carrier-Containing Ternary Amorphous
           Solid Dispersion System Prepared by a Hot Melt Method
    • Authors: Masataka Hanada; Scott V. Jermain, Robert O. Williams
      Abstract: The focus of our study was to employ a solvent-free, thermal process to evaluate the use of a porous carrier in a drug-polymer-porous carrier ternary formulation containing a high drug load (e.g., ≥50% w/w). The purpose of the study was to improve the dissolution properties of the BCS Class II drug, indomethacin (IND), in the ternary formulation. The effect that the selected polymer has on properties of the formulation was studied, and the formulation characteristics of hypromellose (AF15), copovidone (VA64), and polyvinyl alcohol-polyethylene glycol graft copolymer (KIR) was evaluated in order to understand differences in dissolution rates and drug adsorption onto the porous carrier.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.025
       
  • Co-Amorphous API-Small Molecule Mixtures: Considerations in the Choice of
           Co-Formers for Enhancing Dissolution and Oral Bioavailability
    • Authors: Ann Newman; Susan M. Reutzel-Edens, George Zografi
      Abstract: In recent years, co-amorphous systems, containing an active pharmaceutical ingredient (API) and a small molecule co-former have appeared as alternatives to the use of amorphous solid dispersions containing polymer (ASDs), or co-crystals of API and small molecule co-formers, to improve the dissolution and oral bioavailability of poorly soluble crystalline API. This Commentary considers the relative properties of ASDs and co-amorphous systems in terms of methods of preparation; miscibility; glass transition temperature; physical stability, hygroscopicity; and aqueous dissolution.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.024
       
  • Solubilization of a Poorly Soluble b-RAF (Rapidly Accelerated
           Fibrosarcoma) Inhibitor: From Theory to Application
    • Authors: Linda Bao; Le An, Yingqing Ran
      Abstract: The oral bioavailability of a drug candidate is influenced by its permeability, metabolism, and physico-chemical properties. Among the physico-chemical properties, solubility and dissolution rate often are the most critical factors affecting the oral bioavailability of a compound. The increasing challenge for the pharmaceutical industry is to achieve reasonable oral bioavailability of poorly water-soluble drug candidates. G-F is a potent and selective b-raf inhibitor with poor water solubility and moderate permeability, which resulted in an absorption-limited exposure in preclinical safety studies.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.023
       
  • The use of a 2,2’-azobis (2-amidinopropane) dihydrochloride (AAPH)
           stress model as an indicator of oxidation susceptibility for monoclonal
           antibodies
    • Authors: Michelle Z. Dion; Y. John Wang, Daniel Bregante, Wayman Chan, Nisana Andersen, Amy Hilderbrand, Danielle Leiske, Cleo M. Salisbury
      Abstract: Protein oxidation is a major pathway for degradation of biologic drug products. Past literature reports have suggested that AAPH, a free radical generator that produces alkoxyl and alkyl peroxyl radicals, is a useful model reagent stress for assessing the oxidative susceptibility of proteins. Here, we expand the applications of the AAPH model by pairing it with a rapid peptide map method to enable site-specific studies of oxidative susceptibility of monoclonal antibodies (mAbs) and their derivatives for comparison between formats, the evaluation of formulation components, and comparisons across stress models.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.022
       
  • In vivo transgene expression in the pancreas by the intraductal injection
           of naked plasmid DNA
    • Authors: Yuma Yamada; Mai Tabata, Jiro Abe, Masatoshi Nomura, Hideyoshi Harashima
      Abstract: Patients with type I diabetes, which is caused by the destruction of pancreatic islets, now require regular therapeutic injections of insulin. The use of transgene therapy represents an alternate and potent strategy for the treatment of type I diabetes. However, only a limited number of studies regarding in vivo gene delivery targeting the pancreas and islets have been reported. Here, we report on the possibility of in vivo transgene expression in the pancreas by the intraductal injection of naked plasmid DNA (pDNA).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.021
       
  • Drug-Disease Interaction: Effect of inflammation and Nonsteroidal
           Anti-Inflammatory Drugs on Cytochrome P450 Metabolites of Arachidonic Acid
           
    • Authors: Ali Aghazadeh-Habashi; Waheed Asghar, Fakhreddin Jamali
      Abstract: Inflammatory conditions increase cardiovascular (CV) risk. Some nonsteroidal anti-inflammatory drugs (NSAIDs) that are used to treat pain and inflammation are also associated with CV complications. Inflammation, but not NSAIDs, disrupts the balance of vasodilator and vasoconstrictor components of the renin-angiotensin system (RAS) within the heart. Herein, we report the effect of both inflammation and NSAIDs (rofecoxib, celecoxib and meloxicam) on the physiologically active cytochrome P450 (CYP) metabolites of arachidonic acid (ArA) in the rat with adjuvant arthritis (AA).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.020
       
  • Optimization of a Vaginal Suppository Formulation to Deliver SHetA2 as a
           Novel Treatment for Cervical Dysplasia
    • Authors: Sanjida Mahjabeen; Manolya K. Hatipoglu, Vishal Chandra, Doris M. Benbrook, Lucila Garcia-Contreras
      Abstract: Cervical dysplasia induced by the human papilloma virus (HPV) unpredictably progresses to cervical cancer. Therapeutic options are invasive and affect the patient’s quality of life. SHetA2 has demonstrated therapeutic efficacy against human and murine HPV- induced tumors, but its oral bioavailability is
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.018
       
  • Development of a novel amorphous agomelatine formulation with improved
           storage stability and enhanced bioavailability
    • Authors: Panagiotis Barmpalexis; Agni Grypioti, Elisavet Vardaka, Anna Karagianni, Kyriakos Kachrimanis
      Abstract: The present work describes the development of a novel formulation of amorphous agomelatine (AGM) that exhibits enhanced in vitro dissolution rate and bioavailability, as well as improved storage stability. Agomelatine was loaded on a mixture of microcrystalline cellulose with a high specific surface area excipient, namely colloidal silicon dioxide, employing a wet granulation method and the resultant AGM granules were subsequently formulated into immediate release film-coated tablets. Modulated differential scanning calorimetry (MT-DSC), hot-state light microscopy, powder X-Ray diffraction (PXRD), attenuated total reflection ATR-FTIR and micro-Raman spectroscopy revealed that the API existed primarily in the amorphous state within the prepared formulations, with some crystals of polymorph I also present.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.017
       
  • Evaluation of Glass Delamination Risk in Pharmaceutical 10 mL/10R Vials
    • Authors: Dominique Ditter; Alejandra Nieto, Hanns-Christian Mahler, Holger Roehl, Michael Wahl, Joerg Huwyler, Andrea Allmendinger
      Abstract: Glass delamination is characterized by the dissociation of glass flakes from the glass surface. Since glass delamination is time dependent, five vial types were investigated to assess delamination under accelerated stress conditions published as quick tests in literature and compared to stress testing recommended per United States Pharmacopoeia (USP). A broad panel of analytical techniques was employed to test the solution for visible/sub-visible particles and leachables, and characterize topography and composition of the surface.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.016
       
  • How sensitive are transdermal transport predictions by microscopic stratum
           corneum models to geometric and transport parameter input'
    • Authors: Jessica Wen; Soh Myoung Koo, Nancy Lape
      Abstract: While predictive models of transdermal transport have the potential to reduce human and animal testing, microscopic stratum corneum (SC) model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and penetrant transport parameters (e.g. compound diffusivity in lipids). Most microscopic models are limited to a simple rectangular brick-and-mortar SC geometry and do not account for variability across delivery sites, hydration levels, and populations.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.015
       
  • Mechanistic basis of cocrystal dissolution advantage
    • Authors: Fengjuan Cao; Gordon L. Amidon, Naír Rodríguez-Hornedo, Gregory E. Amidon
      Abstract: Current interest in cocrystal development resides in the advantages that the cocrystal may have in solubility and dissolution compared to the parent drug. This work provides a mechanistic analysis and comparison of the dissolution behavior of carbamazepine (CBZ) and its two cocrystals, carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) under the influence of pH and micellar solubilization. A simple mathematical equation is derived based on the mass transport analyses to describe the dissolution advantage of cocrystals.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.014
       
  • Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid
           in Post-Extractive Alveolar Wounds
    • Authors: Ovidio Catanzano; Vittoria D’Esposito, Pietro Formisano, Joshua S. Boateng, Fabiana Quaglia
      Abstract: The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a non-satisfactory healing process. Here we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the post-extractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-05
      DOI: 10.1016/j.xphs.2017.09.026
       
  • Improving the Carprofen Solubility: Synthesis of the Zn2al-Ldh Hybrid
           Compound
    • Authors: Doretta Capsoni; Irene Quinzeni, Giovanna Bruni, Valeria Friuli, Lauretta Maggi, Marcella Bini
      Abstract: The development of efficient strategies for drug delivery is considerably desired. Indeed, often several issues such as the drug solubility, the control of the drug release rate, the targeted delivery of drugs, the drug bioavailability and the minimization of secondary effects still present great obstacles. Different methodologies have been proposed, but the use of nano-hybrids compounds that combine organic and inorganic substances seems particularly promising. An interesting inorganic host is the layered double hydroxide (LDH) with a sheets structure and formula M2+1-x M3+x (OH)2](An-)x/n yH2O (M2+= Zn, Mg; M3+=Al; An- = nitrates, carbonates, chlorides).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-05
      DOI: 10.1016/j.xphs.2017.09.019
       
  • Evaluating Suspension Formulations of Theophylline Cocrystals with
           Artificial Sweeteners
    • Authors: Srinivasulu Aitipamula; Annie B.H. Wong, Parijat Kanaujia
      Abstract: Pharmaceutical cocrystals have garnered significant interest as potential solids to address issues associated with formulation development of drug substances. However, studies concerning the understanding of formulation behaviour of cocrystals are still at the nascent stage. We present results of our attempts to evaluate suspension formulations of cocrystals of an anti-asthmatic drug, theophylline, with two artificial sweeteners. Stability, solubility, drug release and taste of the suspension formulations were evaluated.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-05
      DOI: 10.1016/j.xphs.2017.09.013
       
  • Synthesis, Characterization and Crystal Chemistry of Tasimelteon, a
           Melatonin Agonist, in its Anhydrous and Hemihydrate Forms
    • Authors: Giampiero Ventimiglia; Sonia Bellomi, Giuseppe Barreca, Lorella Giovannelli, Norberto Masciocchi
      Abstract: Two crystalline forms of Tasimelteon, a drug approved by the US FDA for the treatment of non-24-hour sleep-wake disorder, have been studied by single crystal and powder diffraction analyses, TGA, DSC, spectroscopic and optical methods. The synthetic method forming Tasimelteon is described in detail, with its full analytical, spectroscopic and enantiopurity characterization. Solid Tasimelteon hemihydrate, C15H19NO2⋅0.5H2O, is tetragonal with a = b = 7.3573(2) Å, c = 52.062(2) Å, V = 2818.1(2) Å3; Z = 8.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-22
      DOI: 10.1016/j.xphs.2017.09.012
       
  • Process Development and Robust Control of Physical Attributes of an
           Amorphous Drug Substance
    • Authors: Dimitrios Zarkadas; Christopher S. Pridgen, Vincenzo Liotta
      Abstract: Control of physical attributes of amorphous Active Pharmaceutical Ingredients (APIs) can be challenging due to processability issues, their wide variation during processing and the requirement to control them to specific ranges. In this paper, we report our efforts to develop a robust isolation process for Boceprevir, which delivers specific surface areas between 3.0 and 9.4 m2/g. We developed mechanistic process understanding by utilizing a new method to measure glass transition temperature of API suspensions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-22
      DOI: 10.1016/j.xphs.2017.09.010
       
  • Relating observed psychoactive effects to the plasma concentrations of
           delta-9-tetrahydrocannabinol (THC) and its active metabolite: an
           effect-compartment modeling approach
    • Authors: Rakesh Awasthi; Guohua An, Maureen D. Donovan, Laura L. Boles Ponto
      Abstract: The medical use of marijuana is increasing, yet little is known about the exposure-response relationship for its psychoactive effects. It is well known that the plasma concentrations of the principal psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), do not directly correlate to the observed psychoactive effects. The purpose of this research was to use an effect-compartment modeling approach to predict and relate the concentrations of the psychoactive components (THC and its active metabolite) in the “hypothetical” effect-site compartment to the observed psychoactive effects.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-20
      DOI: 10.1016/j.xphs.2017.09.009
       
  • Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and
           Pluronic Lecithin Organogel
    • Authors: Qian Zhang; Yunmei Song, Stephen W. Page, Sanjay Garg
      Abstract: The transdermal delivery of two fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from two commercially available transdermal bases, pluronic lecithin organogel (PLO) and Lipoderm® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin were evaluated. Retention and depth distribution profiles in skin were obtained by tape-stripping and then followed by optical sectioning using multiphoton microscopy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-18
      DOI: 10.1016/j.xphs.2017.09.008
       
  • Evidence that P-glycoprotein inhibitor (elacridar)-loaded nanocarriers
           improve epidermal targeting of an anticancer drug via absorptive cutaneous
           transporters inhibition
    • Authors: Daniela V. Giacone; Vanessa F.M. Carvalho, Soraia K.P. Costa, Luciana B. Lopes
      Abstract: Because P-glycoprotein (P-gp) plays an absorptive role in the skin, its pharmacological inhibition represents a strategy to promote cutaneous localization of anticancer agents that serve as its substrates, improving local efficacy while reducing systemic exposure. Here, we evaluated the ability of a nanoemulsion (NE) co-encapsulating a P-gp inhibitor (elacridar) with the antitumor drug paclitaxel to promote epidermal targeting. Loaded NE displayed a nanometric size (45.2±4.0 nm) and negative zeta potential (-4.2±0.8 mV).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-18
      DOI: 10.1016/j.xphs.2017.09.007
       
  • Manufacture of fibrous dosage forms by wet micro-patterning and drying
    • Authors: Aron H. Blaesi; Nannaji Saka
      Abstract: Recently, we have introduced fibrous dosage forms prepared by the predictable deposition, or 3D-micro-patterning, of a drug-laden fibrous melt on a surface. Such dosage forms enable precisely controlled microstructures and drug release rates, and can be manufactured by an efficient, continuous melt process. However, the applicability of melt-processing to manufacture pharmaceutical dosage forms is limited because the temperatures at which suitable excipients plasticize by melting are greater than the degradation or melting temperatures of many kinds of drugs.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-18
      DOI: 10.1016/j.xphs.2017.08.023
       
  • Impact of experimental variables on the protein binding of tigecycline in
           human plasma as determined by ultrafiltration
    • Authors: Christoph Dorn; Alexander Kratzer, Uwe Liebchen, Michael Schleibinger, Alexandra Murschhauser, Jens Schlossmann, Frieder Kees, Philipp Simon, Martin G. Kees
      Abstract: Tigecycline, a tetracycline derivative, shows atypical plasma-protein-binding behavior. The unbound fraction decreases with increasing concentration at therapeutic concentrations. Moreover, uncertainty exists about the magnitude of tigecyline’s protein binding in man. Unbound fractions between 2.5 and 35% have been reported in plasma from healthy volunteers, and between 25 and 100 % in patients, respectively. In the present study, the protein binding of tigecycline has been investigated by ultrafiltration using different experimental conditions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-16
      DOI: 10.1016/j.xphs.2017.09.006
       
  • Industry Perspective on Contemporary Protein Binding Methodologies:
           Considerations for Regulatory Drug-Drug Interaction and Related Guidelines
           on Highly Bound Drugs
    • Authors: Li Di; Christopher Breen, Rob Chambers, Sean T. Eckley, Robert Fricke, Avijit Ghosh, Paul Harradine, J. Cory Kalvass, Stacy Ho, Caroline A. Lee, Punit Marathe, Everett J. Perkins, Mark Qian, Susanna Tse, Zhengyin Yan, Maciej J. Zamek-Gliszczynski
      Abstract: Regulatory agencies have recently issued drug-drug interaction (DDI) guidelines, which require determination of plasma protein binding (PPB). To err on the conservative side, the agencies recommend that a 0.01 lower limit of fraction unbound (fu) be used for highly bound compounds (>99%), irrespective of the actual measured values. While this may avoid false negatives, the recommendation would likely result in a high rate of false positive predictions, resulting in unnecessary clinical studies and more stringent inclusion/exclusion criteria, which may add cost and time in delivery of new medicines to patients.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-16
      DOI: 10.1016/j.xphs.2017.09.005
       
  • Mechanics of pharmaceutical pellets – Constitutive properties,
           deformation and breakage behavior∗
    • Authors: Alexander Russell; Rok Šibanc, Rok Dreu, Peter Müller
      Abstract: To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing unit operations (for e.g. withstanding mechanical stresses during coating, optional axial compression, handling, packaging, storage and transport conditions), process design should include consideration of precise limits of accurate micro, macro and bulk properties of the constituent pellets.This communication presents a comprehensive intricate database of micro-mechanical properties’ and breakage probability distribution functions of pellets, illustrating the stiffening and strengthening effects of coatings and the softening and weakening effects of structural moisture.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-16
      DOI: 10.1016/j.xphs.2017.08.022
       
  • Selection of Solid-State Plasticizers as Processing Aids for Hot-Melt
           Extrusion
    • Authors: Dipen Desai; Harpreet Sandhu, Navnit Shah, Waseem Malick, Hossein Zia, Wantanee Phuapradit, Siva Ram Kiran Vaka
      Abstract: The objective of the study was to select solid state plasticizers for hot melt extrusion (HME) process. The physical and mechanical properties of plasticizers, in selected binary (polymer: plasticizer) and ternary (API: polymer: plasticizer) systems, were evaluated to assess their effectiveness as processing aids for HME process. Indomethacin (INM) and Eugradit® E PO were selected as model Active Pharmaceutical Ingredient (API) and polymer, respectively. Solubility parameters, thermal analysis and rheological evaluation were used as assessment tools.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-15
      DOI: 10.1016/j.xphs.2017.09.004
       
  • Effect of Water on the Chemical Stability of Amorphous Pharmaceuticals: 2.
           Deamidation of peptides and proteins
    • Authors: Satoshi Ohtake; Shaoxin Feng, Evgenyi Shalaev
      Abstract: Role of water in chemical (in)stability is revisited, with focus on deamidation in freeze-dried amorphous proteins and peptides. Two distinct patterns for deamidation vs. water have been reported, i.e., a consistent increase in rate constant with water, and a “hockey stick”-type behavior. For the latter, deamidation is essentially independent of water at lower water contents, and accelerates when water content increases above a threshold value. Two simple kinetic models are developed to analyze literature-reported relationships between water content and deamidation rate constants.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-15
      DOI: 10.1016/j.xphs.2017.09.003
       
  • Nose to Brain Delivery of Rivastigmine by In-situ Gelling Cationic
           Nanostructured Lipid Carriers: Enhanced Brain Distribution and
           Pharmacodynamics
    • Authors: Preeti Wavikar; Rohan Pai, Pradeep Vavia
      Abstract: Present investigation explores the potential of Nanostructured Lipid Carriers (NLCs) for nose to brain delivery of Rivastigmine (RV), which is further enhanced by incorporating into an in-situ gelling system, increasing retention in nasal cavity. NLC’s having particle size of 123.2±2.3 nm, entrapment efficiency of 68.3±3.4% and zeta potential of 32±1.2 mV was fabricated by a scalable method. Pharmacokinetics showed sustained release of intranasal (IN) and intravenous (IV) NLC’s compared to RV solution by same route, with significantly higher AUC and Thalf.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-15
      DOI: 10.1016/j.xphs.2017.08.024
       
  • The combination of GIS and biphasic to better predict in vivo dissolution
           of BCS class IIb drugs, ketoconazole and raloxifene.
    • Authors: Yasuhiro Tsume; Naoto Igawa, Adam J. Drelich, Gregory E. Amidon, Gordon L. Amidon
      Abstract: The formulation developments and the in vivo assessment of Biopharmaceutical Classification System (BCS) class II drugs are challenging due to their low solubility and high permeability in the human gastrointestinal (GI) tract. Since the GI environment influences the drug dissolution of BCS class II drugs, the human GI characteristics should be incorporated into the in vitro dissolution system to predict bioperformance of BCS class II drugs. An absorptive compartment may be important in dissolution apparatus for BCS class II drugs, especially for bases (BCS IIb) because of high permeability, precipitation and supersaturation.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-15
      DOI: 10.1016/j.xphs.2017.09.002
       
  • Prediction of air entrapment in tableting: An approximate solution
    • Authors: Antonios Zavaliangos; Jeffrey M. Katz, Dominick Daurio, Michael Johnson, Armen Pirjanian, Fernando Alvarez-Nunez
      Abstract: Αn approximate solution is presented for the prediction of air entrapment during tableting. Assuming weak coupling of the deformation of the solid phase, the flow of interstitial air and a set of reasonable additional geometric assumptions, the general problem is reduced to one dimension. Experimental values of air permeability through tablet specimens of commonly used pharmaceutical excipients were obtained using a 3D printed test cell outfitted to a powder rheometer. Using these values, combined with a numerical solution of the governing partial differential equation, parametric studies are presented that demonstrate the importance of permeability, compaction speed, tablet size, and punch-die tolerance on air entrapment.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-15
      DOI: 10.1016/j.xphs.2017.09.001
       
  • Estimation of drug particle size in intact tablets by two dimensional
           X-ray diffractometry
    • Authors: Seema Thakral; Naveen K. Thakral, Raj Suryanarayanan
      Abstract: The average grain size of a crystalline material can be determined from the γ-profile of Debye rings in two-dimensional X-ray diffraction (2D XRD) frames. Our objectives were to: (i) validate the method for organic powders and use it to determine the grain size in intact tablets, and (ii) demonstrate the pharmaceutical application of this technique by determining the grain size of the active pharmaceutical ingredient (API) in marketed formulations. Six sieve fractions of sucrose were prepared and the particle size distribution was confirmed by laser diffraction.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-09
      DOI: 10.1016/j.xphs.2017.08.021
       
  • Mixed Reality (MR) Meets Pharmaceutical Development
    • Authors: W.P. Forrest; M.A. Mackey, V.M. Shah, K.M. Hassell, P. Shah, J.L. Wylie, J. Gopinath, H. Balderhaar, L. Li, W.P. Wuelfing, R. Helmy
      Abstract: As science evolves, the need for more efficient and innovative knowledge transfer capabilities becomes evident. Advances in drug discovery and delivery sciences have directly impacted the pharmaceutical industry, though the added complexities have not shortened the development process. These added complexities also make it difficult for scientists to rapidly and effectively transfer knowledge to offset the lengthened drug development timelines. While webcams, camera phones and iPads have been explored as potential new methods of real-time information sharing, the non-“hands-free” nature and lack of viewer and observer point-of-view render them unsuitable for the R&D laboratory or manufacturing setting.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-01
      DOI: 10.1016/j.xphs.2017.08.020
       
  • Application of x-ray sensors for in-line and non-invasive monitoring of
           mass flow rate in continuous tablet manufacturing
    • Authors: Sudarshan Ganesh; Rachel Troscinski, Nicholas Schmall, Jongmook Lim, Zoltan Nagy, Gintaras Reklaitis
      Abstract: The progress in continuous downstream manufacturing of oral solid doses demands effective real-time process management, with monitoring at its core. This study evaluates the feasibility of using a commercial sensor to measure the mass flow rate of the particulates, a critical process variable in continuous manufacturing. The sensor independently measures x-ray attenuation and cross-correlation velocimetry of particulate flow in real-time. Steady-state flow rates of blends comprised primarily of acetaminophen and microcrystalline-cellulose are monitored using the sensor, with simultaneous weighing scale measurements, in order to calibrate the sensor and investigate the measurement accuracy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-01
      DOI: 10.1016/j.xphs.2017.08.019
       
  • The Influence of Mannitol Hemihydrate on the Secondary Drying Dynamics of
           a Protein Formulation: A Case Study
    • Authors: Jayasree M. Srinivasan; Lindsay A. Wegiel, Lisa M. Hardwick, Steven L. Nail
      Abstract: The objective of this research was to study the atypical secondary drying dynamics observed during the freeze-drying of a formulation consisting of mannitol, disaccharide, and sodium chloride, where “bursts” of water vapor release were observed during secondary drying as detected by comparative pressure measurement. “Thief” samples were removed at the end of primary drying and during secondary drying as the shelf temperature was increased in stepwise fashion. These samples were examined by X-ray powder diffraction (XRPD) and thermal analysis.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-01
      DOI: 10.1016/j.xphs.2017.08.018
       
  • Biorelevant drug solubility enhancement modeled by a linear solvation
           energy relationship
    • Authors: Andreas Niederquell; Martin Kuentz
      Abstract: It is for the pharmaceutical sciences of vital importance to understand how drugs are solubilized in biorelevant media. However, the complexity of fasted state simulated intestinal fluid (FaSSIF) has so far hampered adequate solubility modeling. The present study focuses on apparently neutral compounds at physiological pH and a linear free energy relationship is introduced for biorelevant drug solubilization. Based on literature data of 40 compounds, the Abraham solvation descriptors were calculated from chemical structure to then predict the ratio of solubility enhancement, log(SE) in FaSSIF compared to aqueous buffer solubility at pH 6.5.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-29
      DOI: 10.1016/j.xphs.2017.08.017
       
  • Assessing the impact of charge variants on stability and viscosity of a
           high concentration antibody formulation
    • Authors: Shantanu V. Sule; Jason E. Fernandez, Vincent J. Mecozzi, Yana Kravets, William C. Yang, Pamela Feng, Suli Liu, Li Zang, Allan D. Capili, Tia B. Estey, Kapil Gupta
      Abstract: Characterizing molecular charge variants or isoforms is essential for understanding safety, potency and bioavailability of antibody therapeutics. However, there is little information on how they influence stability and viscosity – properties governing immunogenicity and delivery. To bridge this gap, we studied antibody stability as a function of charge variant content generated via bioreactor process. We were able to systematically vary acidic variant levels as a function of bioreactor harvest time.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-28
      DOI: 10.1016/j.xphs.2017.08.016
       
  • Physiologically-Based Oral Absorption Modelling to Study Gut-Level Drug
           Interactions
    • Authors: John Chung; Filippos Kesisoglou
      Abstract: Physiologically-based oral absorption models are in-silico tools primarily used to guide formulation development and project the clinical performance of formulation variants. This commentary briefly discusses additional oral absorption model applications, focusing on gut level drug interactions. Gut level drug interactions can involve drug degradation, metabolic enzymes, transporters, GI motility modulators, acid reducing agents, and food. The growth in publications reporting physiologically-based oral absorption model utilization and successful pharmacokinetic prediction (e.g after acid reducing agent or food co-administration), indicate that oral absorption models have achieved a level of maturity within the industry particularly over the past 15 years.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-25
      DOI: 10.1016/j.xphs.2017.08.015
       
  • Hot melt extrudates formulated using design space: one simple process for
           both palatability and dissolution rate improvement
    • Authors: Lorena F.B. Malaquias; Heidi L. Schulte, Juliano A. Chaker, Kapish Karan, Thomas Durig, Ricardo N. Marreto, Tais Gratieri, Guilherme M. Gelfuso, Marcílio Cunha-Filho
      Abstract: This work aimed to obtain an optimized itraconazole (ITZ) solid oral formulation in terms of palatability and dissolution rate by combining different polymers using hot melt extrusion (HME), according to a simplex centroid mixture design. For this, the polymers Plasdone® (PVP/VA), Klucel ELF® (HPC) and Soluplus® (SOL) were processed using a laboratory HME equipment operating without recirculation at constant temperature. Samples were characterized by physicochemical assays, as well as dissolution rate and palatability using an E-tongue.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-25
      DOI: 10.1016/j.xphs.2017.08.014
       
  • Pharmacologically safe nano-micelles of Amphotericin B with lipids: NMR
           and molecular docking approach
    • Authors: Faisal Usman; Zaheer ul-Haq, Ruqaiya Khalil, Kittiya Tinpun, Teerapol Srichana
      Abstract: This study presents the mode of interaction, structural features and micellization of AmB with sodium deoxycholate sulphate (SDCS) as small lipid molecule at different ratios, as revealed by molecular docking simulations and NMR. AmB-SDCS micelles were synthesized by single pot rinsing method. Solid state 13C NMR revealed hydrogen bonding as main interaction, occurring at different positions between AmB and SDCS at various ratios. Molecular docking elucidated that AmB-SDCS complex was stabilized by multiple hydrogen bonds as well as Van der Waals forces between SDCS and AmB.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-25
      DOI: 10.1016/j.xphs.2017.08.013
       
  • Characterization of N-Acetyl-Tryptophan Degradation in Protein Therapeutic
           Formulations
    • Authors: Kyle L. Hogan; Danielle Leiske, Cleo M. Salisbury
      Abstract: N-Acetyl-tryptophan (NAT) is used as a stabilizer for preparations of human serum albumin and has more recently been demonstrated to provide oxidative protection for labile Trp residues in monoclonal antibodies. As a component in the formulations of protein therapeutics, NAT is sacrificially degraded; therefore understanding the identity and quantity of NAT degradants potentially formed in these drug products is essential to understanding the potential patient impact of this additive. Here we report a simple reversed phase chromatography approach that allows systematic investigation of NAT degradation in relevant formulations under stressed conditions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-24
      DOI: 10.1016/j.xphs.2017.08.012
       
  • Effect of Polysorbate 20 and Polysorbate 80 on the Higher Order Structure
           
    • Authors: Surinder M. Singh; Swati Bandi, David N.M. Jones, Krishna M.G. Mallela
      Abstract: We examined how polysorbate 20 (PS20; Tween 20) and polysorbate 80 (PS80; Tween 80) affect the higher order structure of a monoclonal antibody (mAb) and its Fab and Fc fragments, using near-UV circular dichroism and 2D NMR. Both polysorbates bind to the mAb with sub-millimolar affinity. Binding causes significant changes in the tertiary structure of mAb with no changes in its secondary structure. 2D 13C-1H methyl NMR indicates that with increasing concentration of polysorbates, the Fab region showed a decrease in crosspeak volumes.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-23
      DOI: 10.1016/j.xphs.2017.08.011
       
  • Professor Samuel H. Yalkowsky: Scientist, Mentor, and Molecular Empath
    • Authors: Paul Myrdal; Ken Morris, Rodolfo Pinal, Neera Jain, Peter Wildfong, George Zografi
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-22
      DOI: 10.1016/j.xphs.2017.08.010
       
  • Targeted drug delivery via folate receptors for the treatment of brain
           cancer: Can the promise deliver'
    • Authors: Jianfeng Guo; Michele Schlich, John F. Cryan, Caitriona M. O’Driscoll
      Abstract: Brain cancers are among the most lethal tumours due to their rapid development and poor prognosis. Despite the existing potential of novel therapeutic strategies for the treatment of brain cancer, the major remaining challenge associated with clinical translation is the lack of effective and safe delivery strategies to ensure drug transport to tumour tissues following systemic administration. Folate receptors, known to overexpress on different types of cancer cells, have been used to develop targeted delivery of therapeutic agents for cancer therapy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-22
      DOI: 10.1016/j.xphs.2017.08.009
       
  • Conformational preference and spectroscopical characteristics of the
           active pharmaceutical ingredient Levetiracetam
    • Authors: Raluca Luchian; Emil Vinţeler, Cosmina Chiş, Mihai Vasilescu, Nicolae Leopold, João P. Prates Ramalho, Vasile Chiş
      Abstract: The analysis of the possible conformers and the conformational change between solid and liquid states of a particular drug molecule are mandatory for describing reliably its spectroscopical properties, but also for understanding the interaction with the receptor and its mechanism of action. Therefore, here we investigated the free energy conformational landscape of levetiracetam (LEV) in gas-phase as well as in water and ethanol, aiming to describe the three-dimensional structure and energetic stability of its conformers.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-22
      DOI: 10.1016/j.xphs.2017.08.008
       
  • Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Folic
           acid
    • Authors: Martin A. Hofsäss; Jacqueline De Souza, Neila M. Silva–Barcellos, Karime R. Bellavinha, Bertil Abrahamsson, Rodrigo Cristofoletti, D.W. Groot, Alan Parr, Peter Langguth, James E. Polli, Vinod P. Shah, Tomokazu Tajiri, Mehul U. Mehta, Jennifer B. Dressman
      Abstract: This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the WHO Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as “not highly soluble”.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-22
      DOI: 10.1016/j.xphs.2017.08.007
       
  • Controlled and Localized Nitric Oxide Precursor Delivery from Chitosan
           Gels to Staphylococcus aureus Biofilms
    • Authors: Sayeed Hasan; Nicky Thomas, Benjamin Thierry, Clive A. Prestidge
      Abstract: Extracellular polymeric substances in bacterial biofilms reduce the penetration of antimicrobials and give rise to extreme recalcitrance and treatment challenges for many persistent biofilms and associated infections. Nitric oxide (NO) is a promising alternative to conventional antimicrobials, but is challenging to deliver at precise concentrations for significant periods in a convenient and non-toxic manner. Here we report a unique NO delivery platform by incorporating the NO precursor isosorbide mononitrate (ISMN) into chitosan gels to facilitate sustained ISMN release and effective delivery.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-22
      DOI: 10.1016/j.xphs.2017.08.006
       
  • Syringe Filling of High-Concentration Monoclonal Antibody Formulation:
           Slow Suck Back Pump Speed Prevented Filling Needle Clogging
    • Authors: Simon Hanslip; Kashappa Goud Desai, Mark Palmer, Stephen Bell, Paul Schofield, Prashant Varma, Frank Roche, James D. Colandene, Thomas M. Smith, Douglas P. Nesta
      Abstract: Partial and/or complete clogging of filling needles occurred during syringe filling of a high-concentration monoclonal antibody formulation. This caused non-vertical liquid flow, which eventually led to the termination of filling. Overcoming this phenomenon was essential to ensure minimal fill weight variation, product waste and manufacturing down-time. The liquid behavior inside the filling needle was studied using glass and stainless steel needles, and demonstrated that effective suck back control was critical for preventing needle clogging.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-22
      DOI: 10.1016/j.xphs.2017.08.005
       
  • PLGA-PEG nanoparticles as potential tool for off-label use of
           N-acetylcysteine in the treatment of diastrophic dysplasia
    • Authors: Enrica Chiesa; Luca Monti, Chiara Paganini, Rossella Dorati, Bice Conti, Tiziana Modena, Antonio Rossi, Ida Genta
      Abstract: Potential off-label therapeutic role of N-Acetylcysteine (N-Ac) was recently demonstrated in the treatment of diastrophic dysplasia (DTD) using mutant DTD mice; its main drawback is the rapid clearance from blood due to the liver metabolism. Our goal was to investigate the potential of PEGylated polylactide-co-glycolide (PLGA-PEG) based nanoparticles (NPs) in order to improve in vivo biodistribution performances and N-Ac pharmacokinetic profile after subcutaneous administration in mice. Results suggest that N-Ac can be effectively loaded into NPs (about 99 μg/mg NPs) using a suitably optimized nanoprecipitation method.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-19
      DOI: 10.1016/j.xphs.2017.08.004
       
  • Dissolving microneedles integrated with liquid crystals facilitate
           transdermal delivery of sinomenine hydrochloride
    • Authors: Zhiping Gui; Xingxing Wu, Shuyan Wang, Yingji Cao, Jun Wan, Qianqian Shan, Zhuanzhuan Yang, Jiwen Zhang, Shuangying Gui
      Abstract: The purpose of this study was to investigate the feasibility of delivering sinomenine hydrochloride (SH) transdermally using a composite dissolving microneedles (DM) which integrated with liquid crystals (H2). The fabricated SH-loaded composite DM was evaluated for their appearance, mechanical strength, irritation, efficiency of transdermal delivery of SH. Results depicted that optimized SH-loaded composite DM had sufficient mechanical strength to pierce into rat skin. The in vitro permeability study in rat skin was successfully performed using Franz diffusion cell which showed that the cumulative permeation of SH in the composite DM were significantly increased compared with H2 group (P
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-19
      DOI: 10.1016/j.xphs.2017.07.027
       
  • Albumin-encapsulated liposomes: A novel drug delivery carrier with
           hydrophobic drugs encapsulated in the inner aqueous core
    • Authors: Yuko Okamoto; Kazuaki Taguchi, Keishi Yamasaki, Mina Sakuragi, Shun’ichi Kuroda, Masaki Otagiri
      Abstract: Liposomes are clinically used in drug delivery, but loading hydrophobic substances is limited to the hydrophobic space of a lipid membrane, despite the fact that it is favorable to encapsulate substances into the inner aqueous core of liposome, from a drug stability of view. We report herein on the preparation of a liposome with bovine serum albumin encapsulated (BSA-liposome). Using this system, it is possible to encapsulate hydrophobic drugs in the inner aqueous core of the liposome based on the hypothesis that the water solubility of hydrophobic drugs is increased when bound to albumin.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-18
      DOI: 10.1016/j.xphs.2017.08.003
       
  • Assessment of Passive Intestinal Permeability Using an Artificial Membrane
           Insert System
    • Authors: Philippe Berben; Joachim Brouwers, Patrick Augustijns
      Abstract: Despite reasonable predictive power of current cell-based and cell-free absorption models for the assessment of intestinal drug permeability, high costs and/or lengthy preparation steps hamper their use. The use of a simple artificial membrane (without any lipids present) as intestinal barrier substitute would overcome these hurdles. In the present study, a set of 14 poorly water-soluble drugs, dissolved in two different media [fasted state simulated/human intestinal fluids (FaSSIF/FaHIF)], were applied to the donor compartment of an artificial membrane insert system (AMI-system) containing a regenerated cellulose membrane.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-18
      DOI: 10.1016/j.xphs.2017.08.002
       
  • On-Chip Preparation of Streptokinase Entrapped in Chitosan Nanoparticles
           Used for Potentially Thrombolytic Therapy
    • Authors: Mohammad Shamsi; Payam Zahedi
      Abstract: The objective of this work was to prepare the streptokinase (SK) entrapped in chitosan nanoparticles (CS NPs) using bulk mixing (BM) and microfluidic (MF) techniques. The physicochemical properties of the samples were characterized by means of scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis for optimizing CS and SK solutions concentrations as well as pH values. The obtained results showed that CS NPs fabricated using MF chip have the most uniform morphology, spherical shape and average diameter of 67±13 nm along with a narrow polydispersity.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-18
      DOI: 10.1016/j.xphs.2017.08.001
       
  • Supplemental Analysis of the Prediction of Hepatic Clearance of Binary
           Mixtures of Bisphenol A and Naproxen Determined in an Isolated Perfused
           Rat Liver Model to Promote the Understanding of Potential
           Albumin-Facilitated Hepatic Uptake Mechanism
    • Authors: Patrick Poulin; Michel Bteich, Sami Haddad
      Abstract: The hepatic clearance (CL) of bisphenol A (BPA) in the isolated perfused rat liver (IPRL) model has been studied for the impact of albumin (ALB) binding and coadministration with naproxen (NAP) in a companion manuscript (Bounakta et al. Xenobiotica. 2017;3:1-13.). We reported that the extrapolations of hepatic CL of BPA, NAP, and the binary mixtures between 2 ALB concentrations did not follow the free drug hypothesis; however, potential ALB-facilitated hepatic uptake mechanism(s) were highly suspected.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-17
      DOI: 10.1016/j.xphs.2017.07.004
       
  • How Predictable are Human Stratum Corneum Lipid/Water Partition
           Coefficients' Assessment and Useful Correlations for Dermal Absorption
           
    • Authors: Johannes M. Nitsche; Gerald B. Kasting
      Abstract: Partition coefficients between human stratum corneum lipids and water (Ksclip/w) are collected or deduced from a variety of sources in a manner that approximately doubles the available data compared to the current state-of-the-art model [Hansen et al., Adv Drug Deliv Rev 65:252-264 (2013)]. An additional datum for water itself in porcine SC that considerably extends the molecular size and lipophilicity range of the dataset is considered. The data are analyzed in terms of an extended linear free energy relationship involving octanol/water partition coefficients, Abraham solvation parameters and a secondary, power law molecular weight dependence.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-14
      DOI: 10.1016/j.xphs.2017.07.026
       
  • Recent topics of research in the characterization and quality control of
           biopharmaceuticals in Japan
    • Authors: Akiko Ishii-Watabe; Hiroko Shibata, Akira Harazono, Masashi Hyuga, Masato Kiyoshi, Satoshi Saitoh, Takafumi Iwura, Tetsuo Torisu, Yukihiro Goda, Susumu Uchiyama
      Abstract: The research and development of next-generation innovative medicines is a prominent interest of both the government and industries in Japan. On June 29, 2017, a kickoff meeting of a new research group focused on the quality issues of biopharmaceuticals was held in Tokyo with Prof. John Carpenter as an invited guest. The group’s research focuses mainly on the evaluation and control of protein aggregates/subvisible particles in drug products, but the research topics also include glycan analysis, host-cell protein evaluation, bioassay validation, and analytical quality-by-design.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-09
      DOI: 10.1016/j.xphs.2017.07.024
       
  • Dry mechanochemical synthesis of caffeine / oxalic acid cocrystals and
           their evaluation by powder X-ray diffraction and chemometrics
    • Authors: Yuta Otsuka; Akira Ito, Masaki Takeuchi, Hideji Tanaka
      Abstract: We report the effects of dry mechanochemical synthesis conditions on the crystallization of caffeine and oxalic acid 2:1 cocrystal. Caffeine anhydrate (CA) and oxalic acid (OX) dihydrate were grinded at various temperatures, rotation speeds and grinding time. The cocrystal was also synthesized by an organic solvent evaporation method, as a reference. The produced samples were measured by a powder X-ray diffraction (PXRD) analysis. The PXRD spectra suggest that the grinded cocrystal has a lower crystallinity than the evaporated one.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-07
      DOI: 10.1016/j.xphs.2017.07.025
       
  • In vitro and in situ characterization of triterpene glycosides from
           Cimicifuga racemosa extract
    • Authors: L. Disch; K. Forsch, B. Siewert, J. Drewe, G. Fricker
      Abstract: Cimicifuga racemosa products are widely used in the treatment of climacteric symptoms. Aim was to evaluate Cimicifuga racemosa extract Ze 450 according Biopharmaceutics classification system (BCS).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-04
      DOI: 10.1016/j.xphs.2017.07.023
       
  • Optimization of acetalated dextran based nanocomposite microparticles
           (nCmP) for deep lung delivery of therapeutics via spray drying
    • Authors: Zimeng Wang; Samantha A. Meenach
      Abstract: Nanocomposite microparticle (nCmP) systems exhibit promising potential in the application of therapeutics for pulmonary drug delivery. This work aimed to identify the optimal spray drying condition(s) to prepare nCmP with specific drug delivery properties including: small aerodynamic diameter, effective nanoparticle redispersion upon nCmP exposure to an aqueous solution, high drug loading, and low water content. Acetalated dextran (Ac-Dex) was used to form nanoparticles, curcumin was used as a model drug, and mannitol was the excipient in the nCmP formulation.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-04
      DOI: 10.1016/j.xphs.2017.07.022
       
  • Sample size for tablet compression and capsule filling events during
           process validation
    • Authors: Naseem Ahmad Charoo; Mark Durivage, Ziyaur Rahman, Mohamad Haitham Ayad
      Abstract: During solid dosage form manufacturing, the uniformity of dosage units (UDU) is ensured by testing samples at two stages i.e. blend stage and tablet compression or capsule/powder filling stage. The aim of this work is to propose a sample size selection approach based on quality risk management principles for process performance qualification (PPQ) and continued process verification (CPV) stages by linking UDU to potential formulation and process risk factors. Bayes Success run theorem appeared to be the most appropriate approach among various methods considered in this work for computing sample size for PPQ.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-02
      DOI: 10.1016/j.xphs.2017.07.021
       
  • Deoxycholic acid-conjugated polyethylenimine for delivery of heme
           oxygenase-1 gene in rat ischemic stroke model
    • Authors: Jungju Oh; Min Sang Lee, Ji Hoon Jeong, Minhyung Lee
      Abstract: An efficient gene carrier to the brain is required for successful gene therapy of ischemic stroke. In this study, deoxycholic acid-conjugated polyethylenimine (DA-PEI) was synthesized and evaluated as a heme oxygenase-1 (HO-1) gene carrier for ischemic stroke gene therapy. Gel retardation assay and heparin competition assay showed that DA-PEI formed a stable complex with plasmid DNA (pDNA). In vitro transfection assays with the luciferase gene showed that DA-PEI had higher transfection efficiency than polyethylenimine (25 kDa, PEI25k) and lipofectamine in Neuro2A cells.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-02
      DOI: 10.1016/j.xphs.2017.07.020
       
  • Structural characterization and physicochemical stability profile of a
           double mutant heat labile toxin (dmLT) protein based adjuvant
    • Authors: Vishal M. Toprani; John M. Hickey, Neha Sahni, Ronald T. Toth, George A. Robertson, C. Russell Middaugh, Sangeeta B. Joshi, David B. Volkin
      Abstract: A novel protein adjuvant double mutant E.coli heat labile toxin, LT(R192G/L211A) or dmLT, is in preclinical and early clinical development with various vaccine candidates. Structural characterization and formulation development of dmLT will play a key role in its successful process development, scale-up/transfer and commercial manufacturing. This work describes extensive analytical characterization of structural integrity and physicochemical stability profile of dmLT from a lyophilized clinical formulation.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-02
      DOI: 10.1016/j.xphs.2017.07.019
       
  • Overcoming Challenges with Intravenous Administration of an
           Investigational Protein Therapeutic
    • Authors: Shuai Shi; Venus Hashemi, Shao-Chun Wang, Jiong Yang, Monica (Mei) Yang, Andrew Semple, Chakravarthy Narasimhan, Valentyn Antochshuk
      Abstract: Piggyback infusion has been widely used in the clinic with most applications in a non-concurrent fashion for the purpose of administration convenience. In the present study, we demonstrated the application of concurrent piggyback to overcome challenges with intravenous (IV) administration of a salt-sensitive investigational protein. This setup consists of a syringe line containing drug admixture prepared in water-for-injection (WFI) which is connected to a 0.9% sodium chloride line to keep vein open (“KVO line”).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-01
      DOI: 10.1016/j.xphs.2017.07.018
       
  • Melt-Cast Noninvasive Ocular Inserts for Posterior Segment Drug Delivery
    • Authors: Sai Prachetan Balguri; Goutham R. Adelli, Akshaya Tatke, Karthik Yadav Janga, Prakash Bhagav, Soumyajit Majumdar
      Abstract: The objective of the present study is to evaluate the utility of melt-cast, topical, ocular inserts for delivery of drugs with different physicochemical properties. The model drugs tested include indomethacin (IN), ciprofloxacin Hydrochloride (CIP) and prednisolone sodium phosphate (PSP). Melt-cast method was used to fabricate ophthalmic inserts. Poly (ethylene oxide) N10, a semi-crystalline thermoplastic polymer (PE0 N10; Mol.wt: 100 kDa) was used as the matrix forming material. Polymeric insert units (4 x 2 x 0.2 mm) with a 10% w/w drug load were tested for in vitro release, transmembrane permeability and in vivo ocular tissue distribution.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-01
      DOI: 10.1016/j.xphs.2017.07.017
       
  • Concept: The use of targeted immunoaffinity proteomics for routine
           assessment of in vitro enzyme induction
    • Authors: Caroline MacLean; Frederik Weiß, Oliver Poetz, Thomas Ebner
      Abstract: In vitro investigations on enzyme induction are indispensable for assessment of drug-drug interactions of drug candidates. Regulatory bodies require measurement of changes of mRNA in cultured human hepatocytes. However, such data provide only indirect assessments of effects of enzyme induction in vivo. We describe the quantification of cytochrome P450 (CYP) enzyme protein levels by LC-MS for the routine assessment of enzyme induction. Protein concentration of CYP1A2, 2B6, 3A4 and 2C8 were measured in human hepatocytes after incubation with prototypical enzyme inducers and drug candidate BI-X using an antibody-based capturing method.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-01
      DOI: 10.1016/j.xphs.2017.07.016
       
  • A flow imaging microscopy based method using mass-to-volume ratio to
           derive the porosity of PLGA microparticles
    • Authors: A.S. Sediq; S.K.D. Waasdorp, M.R. Nejadnik, M.M.C. van Beers, J. Meulenaar, R. Verrijk, W. Jiskoot
      Abstract: The release of drugs from poly(lactic-co-glycolic acid) (PLGA) microparticles depends to a large extent on the porosity of the particles. Therefore, porosity determination of PLGA microparticles is extremely important during pharmaceutical product development. Currently, mercury intrusion porosimetry (MIP) is widely used despite its disadvantages, such as the need for a large amount of sample (several hundreds of milligrams) and residual toxic waste. Here, we present a method based on estimation of the volume of a known mass (a few milligrams) of particles using Micro-Flow Imaging (MFI) to determine microparticle batch porosity.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-26
      DOI: 10.1016/j.xphs.2017.07.015
       
  • Assessing the Detection Limit of a Minority Solid-State Form of a
           Pharmaceutical by 1H Double-Quantum MAS NMR Spectroscopy
    • Authors: Keisuke Maruyoshi; Dinu Iuga, Abigail E. Watts, Colan E. Hughes, Kenneth D.M. Harris, Steven P. Brown
      Abstract: The lower detection limit for two distinct crystalline phases by 1H magic-angle spinning (MAS) solid-state NMR is investigated for a minority amount of cimetidine (anhydrous polymorph A) in a physical mixture with the anhydrous hydrochloride salt of cimetidine. Specifically, two-dimensional 1H double-quantum (DQ) MAS spectra of polymorph A and the anhydrous hydrochloride salt constitute fingerprints for the presence of each of these solid forms. For solid-state NMR data recorded at a 1H Larmor frequency of 850 MHz and a MAS frequency of 30 kHz on ∼10 mg of sample, it is shown that, by following the pair of cross peaks at a 1H DQ frequency of 7.4 + 11.6 = 19.0 ppm that are unique to polymorph A, the level of detection for polymorph A in a physical mixture with the anhydrous hydrochloride salt is a concentration of 1% w/w.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-25
      DOI: 10.1016/j.xphs.2017.07.014
       
  • Comparative Characterization of Crofelemer Samples using Data Mining and
           Machine Learning Approaches with Analytical Stability Data Sets
    • Authors: Maulik K. Nariya; Jae Hyun Kim, Jian Xiong, Peter A. Kleindl, Asha Hewarathna, Adam C. Fisher, Sangeeta B. Joshi, Christian Schöneich, M. Laird Forrest, C. Russell Middaugh, David B. Volkin, Eric J. Deeds
      Abstract: There is growing interest in generating physicochemical and biological analytical data sets to compare complex mixture drugs, for example products from different manufacturers. In this work, we compare various crofelemer samples prepared from a single lot by filtration with varying molecular weight cut-offs combined with incubation for different times at different temperatures. The two preceding manuscripts describe experimental data sets generated from analytical characterization of fractionated and degraded crofelemer samples.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-22
      DOI: 10.1016/j.xphs.2017.07.013
       
  • The botanical drug substance crofelemer as a model system for comparative
           characterization of complex mixture drugs
    • Authors: Peter A. Kleindl; Jian Xiong, Asha Hewarathna, Olivier Mozziconacci, Maulik K. Nariya, Adam C. Fisher, Eric J. Deeds, Sangeeta B. Joshi, C. Russell Middaugh, Christian Schöneich, David B. Volkin, M. Laird Forrest
      Abstract: Crofelemer is a botanical polymeric proanthocyanidin that inhibits chloride channel activity and is used clinically for treating HIV-associated secretory diarrhea. Crofelemer lots may exhibit significant physicochemical variation due to the natural source of the raw material. A variety of physical, chemical, and biological assays were utilized to identify potential critical quality attributes (CQAs) of crofelemer, which may be useful in characterizing differently sourced and/or processed drug products.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-22
      DOI: 10.1016/j.xphs.2017.07.012
       
  • Phase Behavior of a Fc-fusion Protein Reveals Generic Patterns of
           Ion-specific Perturbation on Protein-Protein Interactions
    • Authors: Le Zhang; Lei Yu, Jian Zhang-Van Enk, Gang Huang, Jifeng Zhang
      Abstract: Modulation of liquid-liquid phase separation temperature (Tph) for liquid-liquid phase separation (LLPS) of a Fc-fusion protein was studied at pH values below, near and above its pI where the net charge of the protein was positive, neutral and negative, respectively, in KF, KCl, KSCN and MgCl2 solutions. At the pH value near the pI, the monotonic drop in Tph for all the salt solutions suggests that both the anion and cation can disrupt attractive protein-protein interactions, effectively salting-in the protein.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-21
      DOI: 10.1016/j.xphs.2017.07.011
       
  • Formation Mechanism and in Vitro Evaluation of Risperidone-containing PLGA
           Microspheres Fabricated by Ultra-fine Particle Processing System
    • Authors: Zhengwei Huang; Xiaona Chen, Han Fu, Xinguo Wen, Cheng Ma, Jiwen Zhang, Chuanyu Wu, Ying Huang, Xin Pan, Chuanbin Wu
      Abstract: Ultra-fine particle processing system (UPPS) was developed previously by our group to provide a new solution to microspheres fabrication. The UPPS was supposed to possess many featured advantages, but the microspheres formation mechanism during UPPS processing was still unknown. The objective of this study was to perform the formation mechanism investigation and in vitro evaluation on risperidone-containing PLGA microspheres (RIS-PLGA MS) fabricated by UPPS. Evaporation profile and viscosity of the PLGA containing solutions were considered as the critical factors for the microspheres formation mechanism, and were determined in present study.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-20
      DOI: 10.1016/j.xphs.2017.07.010
       
  • Drug Delivery Innovations to Address Global Health Challenges for
           Pediatric and Geriatric Populations (through improvements in patient
           compliance)
    • Authors: Joshua Boateng
      Abstract: Despite significant advances in pharmaceutical and biotechnological drug discovery, the global population is plagued with many challenging diseases. These are further compounded by anticipated explosion in an ageing population, which presents several problems such as polypharmacy, dysphagia and neurological conditions, resulting in non-compliance and disease complications. For antibiotics, poor compliance, can result in development of drug resistant infections which can be fatal. Further, children, especially, in developing countries die unnecessarily from easily treatable diseases (e.g.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-19
      DOI: 10.1016/j.xphs.2017.07.009
       
  • Impact of Magnetic Stirring on Stainless Steel Integrity - Effect on
           Biopharmaceutical Processing
    • Authors: Christopher Thompson; Kelly Wilson, Yoen Joo Kim, Min Xie, William K. Wang, Michaela Wendeler
      Abstract: Stainless steel containers are widely used in the pharmaceutical and biopharmaceutical industry for the storage of buffers, process intermediates, and purified drug substance. They are generally held to be corrosion resistant, biocompatible, and non-reactive, although it is well established that trace amounts of metal ions can leach from stainless steel equipment into biopharmaceutical products. We report here that the use of stainless steel containers in conjunction with magnetic stirring bars leads to significantly aggravated metal contamination, consisting both of metal particles and significantly elevated metal ions in solution, the degree of which is several orders of magnitude higher than described for static conditions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-19
      DOI: 10.1016/j.xphs.2017.07.008
       
  • Structure-performance relationships of temperature-responsive
           PLGA-PEG-PLGA gels for sustained release of BMP-2
    • Authors: A. Santoveña; C. Monzón, C. Alvarez-Lorenzo, C. del Rosario, A. Delgado, C. Evora, A. Concheiro, M. Llabrés, J.B. Fariña
      Abstract: PLGA-PEG-PLGA synthesis conditions have an impact on the physicochemical features of the copolymer and its usefulness as biomaterial. This study reports on an analysis of the composition and structural properties of PLGA-PEG-PLGA copolymers applying a variety of analytical techniques. Viscoelastic properties and particularly the temperature-responsive behavior of PLGA-PEG-PLGA showed a marked dependence on copolymer structural features. Physicochemical and biological properties, such as bioadhesion, biocompatibility and cell viability, of the raw copolymers and their gels were also evaluated.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-18
      DOI: 10.1016/j.xphs.2017.07.007
       
  • Study of rheology and polymer adsorption onto drug nanoparticles in
           pharmaceutical suspensions produced by nano milling
    • Authors: Renata Negrini; Simone Aleandri, Martin Kuentz
      Abstract: Nanosuspensions provide a drug delivery approach to cope with erratic absorption of poorly water-soluble compounds. Despite of extensive research over the last years, there are still open pharmaceutical challenges so it is often unclear how quality attributes such as viscosity and physical stability are generated, which requires a more thorough study of the colloidal structures and interactions in nanosuspensions. In this study, diffusing wave spectroscopy and microfluidics-based rheology were used for the first time to assess pharmaceutical nanosuspensions that were obtained by wet milling.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-18
      DOI: 10.1016/j.xphs.2017.07.006
       
  • Understanding the delamination risk of a tri-layer tablet using
           mini-piloting tools
    • Authors: Jing Tao; Sophia Robertson-Lavalle, Preetanshu Pandey, Sherif Badawy
      Abstract: A multi-layer tablet is one of the formulation options utilized to mitigate chemical and/or physical incompatibility between different drug substances. Feasibility studies of multi-layer tablets are often conducted using round flat-faced punch tooling. However the link between different tooling designs and multi-layer tablet performance is not well established. This study uses a prototype tri-layer tablet and examines tooling design considerations when conducting small-scale studies to gauge the risk of interfacial defects.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-15
      DOI: 10.1016/j.xphs.2017.07.005
       
  • Crystalline Polymorphism Emerging from a Milling Induced Amorphous form:
           The Case of Chlorhexidine Dihydrochloride
    • Authors: E. Elisei; J.F. Willart, F. Danède, J. Siepmann, F. Siepmann, M. Descamps
      Abstract: In this paper, solid state amorphization induced by mechanical milling is shown to be a useful tool to explore the polymorphism of drugs and their mechanism of devitrification. We show in particular how the recrystallization of amorphous chlorhexidine dihydrochloride obtained by milling reveals a complex polymorphism that involves several polymorphic forms. Two new crystalline forms are identified, one of them appearing as a highly disordered precursor state which however clearly differs from the amorphous one.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-14
      DOI: 10.1016/j.xphs.2017.07.003
       
  • On the use of non-steroidal anti-inflammatory drugs as rheology modifiers
           for surfactant solutions
    • Authors: Pasquino Rossana; Bruno De Gennaro, Danila Gaudino, Nino Grizzuti
      Abstract: Surfactant molecules can give rise to different morphological structures, depending on numerous parameters such as temperature, surfactant concentration and salinity. Specifically, the salt content can be easily tuned in a way to induce morphological transitions and modulate the rheological response. It is shown that non steroidal anti-inflammatory drugs can be used in the same way as classical binding salts in changing the rheological properties of the resulting gel-like system. On the one hand, the experimental results show that by tuning small details in the molecular conformation of the drug and its concentration in the micellar solution it is possible to obtain the desired mechanical response.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-13
      DOI: 10.1016/j.xphs.2017.07.002
       
  • Producing Amorphous Solid Dispersions via co-Precipitation and Spray
           Drying: Impact to Physicochemical and Biopharmaceutical Properties
    • Authors: Amanda K.P. Mann; Luke Schenck, Athanas Koynov, Alfred C.F. Rumondor, Xiaoling Jin, Melanie Marota, Chad Dalton
      Abstract: Many small molecule active pharmaceutical ingredients (APIs) exhibit low aqueous solubility, and benefit from generation of amorphous dispersions of the API and polymer to improve their dissolution properties. Spray drying and hot melt extrusion are two common methods to produce these dispersions; however, for some systems these approaches may not be optimal, and it would be beneficial to have an alternative route. Herein, amorphous solid dispersions of Compound A, a low solubility weak acid, and copovidone were made by conventional spray drying and co-precipitation.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-12
      DOI: 10.1016/j.xphs.2017.07.001
       
  • Chemical stability of the botanical drug substance Crofelemer: a model
           system for comparative characterization of complex mixture drugs
    • Authors: Asha Hewarathna; Olivier Mozziconacci, Maulik K. Nariya, Peter A. Kleindl, Jian Xiong, Adam C. Fisher, Sangeeta B. Joshi, C. Russell Middaugh, M. Laird Forrest, David B. Volkin, Eric J. Deeds, Christian Schöneich
      Abstract: As the second of a three part series of articles in this issue concerning the development of a mathematical model for comparative characterization of complex mixture drugs using Crofelemer (CF) as a model compound, this work focuses on the evaluation of the chemical stability profile of CF. CF is a biopolymer containing a mixture of proanthocyanidin oligomers which are primarily composed of gallocatechin with a small contribution from catechin. CF extracted from drug product was subjected to molecular weight-based fractionation and thiolysis.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-05
      DOI: 10.1016/j.xphs.2017.06.022
       
  • Computational Modeling of Polymeric Physicochemical Properties for
           Formulation Development of a Drug Containing Basic Functionality
    • Authors: Vinod L. Gaikwad; Neela M. Bhatia, Indrajeet Singhvi, Kakasaheb R. Mahadik, Manish S. Bhatia
      Abstract: In the present research, predictive models were developed by correlating polymeric properties with characteristics of a formulation containing a drug with basic heterocycle (glipizide). Glipizide tablets containing different polymers from three categories (immediate, moderate and extended release) were prepared and evaluated. Dissolution kinetics indicated Korsmeyer-peppas as the best fit model, whereas transportability was influenced by release rate and hydrophobicity of the drug. Calculated polymeric descriptors were correlated with formulation properties for the development of predictive quantitative structure-property relationship models.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-05
      DOI: 10.1016/j.xphs.2017.06.021
       
  • Development of Maltodextrin Based Immediate Release Tablets using an
           Integrated Twin-Screw Hot Melt Extrusion and Injection Molding Continuous
           Manufacturing Process
    • Authors: Vibha Puri; Dave Brancazio, Parind M. Desai, Keith D. Jensen, Jung-Hoon Chun, Allan S. Myerson, Bernhardt L. Trout
      Abstract: The combination of hot melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug containing immediate release tablets. Further, studies that have applied the HME-IM process to molded tablets have used a non-continuous two-step approach. The current study develops maltodextrin (MDX) based extrusion molded immediate release tablets for a crystalline drug (griseofulvin, GRIS) using an integrated twin-screw HME-IM continuous process.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-03
      DOI: 10.1016/j.xphs.2017.06.020
       
  • Parameters affecting the enhanced permeability and retention effect: the
           need for patient selection
    • Authors: Az Alddien Natfji; Divyashree Ravishankar, Helen M.I. Osborn, Francesca Greco
      Abstract: The enhanced permeability and retention (EPR) effect constitutes the rationale by which nanotechnologies selectively target drugs to tumors. Despite promising pre-clinical and clinical results, these technologies have, in our view, underachieved compared to their potential, possibly due to a suboptimal exploitation of the EPR effect. Here, we have systematically analyzed clinical data to identify key parameters affecting the extent of the EPR effect. An analysis of 17 clinical studies showed that the magnitude of the EPR effect was varied and was influenced by tumor type and size.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-29
      DOI: 10.1016/j.xphs.2017.06.019
       
  • A Formulation Development Approach to Identify and Select Stable
           Ultra-High Concentration Monoclonal Antibody Formulations with Reduced
           Viscosities
    • Authors: Neal Whitaker; Jian Xiong, Samantha E. Pace, Vineet Kumar, C. Russell Middaugh, Sangeeta B. Joshi, David B. Volkin
      Abstract: High protein concentration formulations are required for low volume administration of therapeutic antibodies targeted for subcutaneous, self-administration by patients. Ultra-high concentrations (≥ 150 mg/mL) can lead to dramatically increased solution viscosities, which in turn can lead to stability, manufacturing and delivery challenges. In this study, various categories and individual types of pharmaceutical excipients and other additives (58 in total) were screened for their viscosity reducing effects on two different monoclonal antibodies (mAbs).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-28
      DOI: 10.1016/j.xphs.2017.06.017
       
  • Developing quantitative in vitro-in vivo correlation (IVIVC) for
           fenofibrate immediate release formulations with the biphasic
           dissolution-partition test method
    • Authors: Hao Xu; Yi Shi, Socrates Vela, Patrick Marroum, Ping Gao
      Abstract: This study is to evaluate three fenofibrate formulations including Fournier® 200 mg capsule, Lipidil® 145 mg tablet, and a clinical HME 160 mg tablet by an in vitro biphasic method. Key experimental parameters were evaluated including the selection of biorelevant media, the USP IV flowrate and the USP paddle speed. Varying the hydrodynamic condition resulted in a significant impact on FEN concentration time profiles in both aqueous and octanol phases for these formulations.In vivo pharmacokinetic profiles of the HME tablet, the Lipidil tablet and Fournier capsule under the fasting and low fat fed states are reported.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-27
      DOI: 10.1016/j.xphs.2017.06.018
       
  • Regulatory Perspectives on Continuous Pharmaceutical Manufacturing: Moving
           from Theory to Practice September 26-27, 2016, International Symposium on
           the Continuous Manufacturing of Pharmaceuticals
    • Authors: Moheb M. Nasr; Markus Krumme, Yoshihiro Matsuda, Bernhardt L. Trout, Clive Badman, Salvatore Mascia, Charles L. Cooney, Keith D. Jensen, Alastair Florence, Craig Johnston, Konstantin Konstantinov, Sau L. Lee
      Abstract: Continuous manufacturing plays a key role in enabling the modernization of pharmaceutical manufacturing. The fate of this emerging technology will rely, in large part, on the regulatory implementation of this novel technology. This paper, which is based on the 2nd International Symposium on the Continuous Manufacturing of Pharmaceuticals, describes not only the advances that have taken place since the first ISCMP in 2014, but the regulatory landscape that exists today. Key regulatory concepts including, Quality Risk Management, batch definition, control strategy, process monitoring and control, Real Time Release Testing, data processing and management, and process validation/verification are outlined.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-26
      DOI: 10.1016/j.xphs.2017.06.015
       
  • In vitro and in vivo skin distribution of 5α-reductase inhibitors loaded
           into liquid crystalline nanoparticles
    • Authors: Thiagarajan Madheswaran; Rengarajan Baskaran, Bong Kyu Yoo, Prashant Kesharwani
      Abstract: In this study, we developed positively charged liquid crystalline nanoparticles (LCN) coated with chitosan (CHI) to enhance the skin permeation and distribution of 5α-reductase inhibitors for the treatment of androgenetic alopecia. LCN and surface-modified LCN (CHI-LCN) were prepared by ultrasonication method, and their physicochemical properties were characterized. In vitro and in vivo skin permeation and retention were studied using porcine abdominal skin and mice skin by using the Franz diffusion cell.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-24
      DOI: 10.1016/j.xphs.2017.06.016
       
  • An Investigation of Oral Exposure Variability and Formulation Strategy: A
           Case Study of PI3K-δ Inhibitor and Physiologically Based Pharmacokinetic
           Modeling in Beagle Dogs
    • Authors: Po-Chang Chiang; Jodie Pang, Jia Liu, Laurent Salphati
      Abstract: It is well acknowledged that drugs with poor aqueous solubility are often associated with poor oral absorption. Fortunately, drugs with a basic pKa can take advantage of solubilization in the stomach under the acidic environment to improve exposure. Consequently, high in vivo variability is often observed when stomach pH is altered. When issue encountered, enabling formulations are often used to solve the problem. However, each enabling formulation has its limitations and the situation can be further complicated by other ADME parameters.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-24
      DOI: 10.1016/j.xphs.2017.06.014
       
  • Electrospray synthesis of PLGA nanoparticles encapsulating peptides to
           enhance proliferation of antigen-specific CD8+ T cells
    • Authors: Britta Furtmann; Justin Tang, Sven Kramer, Thomas Eickner, Frank Luderer, Gert Fricker, Alessandro Gomez, Bianca Heemskerk, Peter S. Jähn
      Abstract: Polymer nanoparticles (NP) are of escalating interest for their application as immune stimulatory pharmaceutics. The production of nanosized carrier systems is currently being widely investigated, but commonly used techniques, such as the double emulsion technique, are limited by shortcomings of low encapsulation efficiency and poor control over size distribution. In this study, the electrospray technique was successfully implemented and optimized to produce monodisperse 200 nm poly (lactide-co glycolide) (PLGA) nanoparticles.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-24
      DOI: 10.1016/j.xphs.2017.06.013
       
  • Gaining Thermodynamic Insight from Distinct Glass Formation Kinetics of
           Structurally Similar Organic Compounds
    • Authors: Arjun Kalra; Paul Luner, Lynne S. Taylor, Stephen R. Byrn, Tonglei Li
      Abstract: Thermodynamic and kinetic aspects of crystallization of 12 structurally similar organic compounds were investigated from the supercooled liquid state by calorimetric and rheological measurements. Based on their crystallization behaviors, these compounds were divided into three categories: stable glass formers, poor glass formers, and good glass formers with poor stability on reheating. Correlation was sought between thermodynamic quantities and glass formation based on nucleation and crystal growth theories.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-22
      DOI: 10.1016/j.xphs.2017.06.012
       
  • Sensitivity Analysis and Uncertainty Quantification in Pulmonary Drug
           Delivery of Orally Inhaled Pharmaceuticals
    • Authors: Jun Lu; Jinxiang Xi, Joseph E. Langenderfer
      Abstract: In spite of widespread use of modeling tools in inhalation dosimetry, it remains difficult to quantify the output uncertainties when subjected to various sources of input variability. This study aimed to develop a computational model that can quantify the input sensitivity and output uncertainty in pulmonary drug delivery by coupling probabilistic analysis package NESSUS with ANSYS Fluent. An image-based mouth-lung model was used to simulate the transport and deposition of drug particles and variability in particle size, density, and inhalation speed were considered.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-20
      DOI: 10.1016/j.xphs.2017.06.011
       
  • Population Pharmacokinetics of Tobramycin Inhalation Solution in Pediatric
           Patients with Cystic Fibrosis
    • Authors: Xinting Wang; Stephan Koehne-Voss, SivaNaga S. Anumolu, Jing Yu
      Abstract: Tobramycin inhalation solution (TOBI) given as a twice-daily inhalation of nebulized aerosols of 300 mg is approved for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients over 6 years of age. To investigate tobramycin pharmacokinetics (PK) after inhalation of TOBI in pediatric CF patients below 7 years, a population PK approach was used to evaluate tobramycin PK data in patients 6 months to 44 years of age from four clinical studies. The final model used a two-compartmental, first-order absorption model with effect of body mass index on the apparent central volume of distribution.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-17
      DOI: 10.1016/j.xphs.2017.06.010
       
  • Mapping the Binding Interface in a Non-covalent Size Variant of a
           Monoclonal Antibody Using Native Mass Spectrometry, Hydrogen/deuterium
           Exchange Mass Spectrometry and Computational Analysis
    • Authors: Yuetian Yan; Hui Wei, Sutjano Jusuf, Stanley R. Krystek, Jie Chen, Guodong Chen, Richard T. Ludwig, Li Tao, Tapan K. Das
      Abstract: Variants of monoclonal antibody containing an extra light chain has been reported in protein products1-3. Due to potential impact on potency and immunogenicity, it is important to understand the formation mechanism of such variants so that appropriate control strategies can be implemented to assure product quality. In a model monoclonal antibody, we observed a size variant with an extra light chain non-covalently associated with the monomer (later named as “1.2mer”). The interaction between monomer and the extra light chain was characterized by native spray and hydrogen/deuterium exchange mass spectrometry (HDX MS) techniques.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-17
      DOI: 10.1016/j.xphs.2017.06.009
       
  • Pulmonary Administration of Soluble Antigen Arrays is Superior to Antigen
           in Treatment of Experimental Autoimmune Encephalomyelitis
    • Authors: Christopher Kuehl; Sharadvi Thati, Bradley Sullivan, Joshua Sestak, Michael Thompson, Teruna Siahaan, Cory Berkland
      Abstract: Antigen-specific immunotherapy (ASIT) has been used to hyposensitize patients to allergens and offers an enticing approach for attenuating autoimmune diseases. Applying ASIT to mucosal surfaces such as the lungs may engage unique immune response pathways to improve efficacy. Pulmonary delivery of soluble antigen arrays (SAgAs) was explored in mice with experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. SAgAs were designed to impede immune response to autoantigen epitopes and are composed of a hyaluronan backbone with peptides PLP139-151 and LABL, a disease-causing proteolipid peptide epitope and an ICAM-1 ligand, respectively.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-15
      DOI: 10.1016/j.xphs.2017.06.008
       
  • Closing the Gap: Counting and Sizing of Particles Across Submicron Range
           by Flow Cytometry in Therapeutic Protein Products
    • Authors: Liling Zhang; Shuai Shi, Valentyn Antochshuk
      Abstract: Quantification and size distribution characterization of subvisible particles in parenteral biopharmaceutics, present as both proteinaceous and nonproteinaceous particles in the size range from 0.1-100 μm, are important for biopharmaceutical industry due to their potential safety and efficacy implications. While a number of analytical techniques are available to count and size subvisible particles, characterization of particles ≤ 2 μm remains a significant challenge due to technical limitations of existing particle counting instruments.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-15
      DOI: 10.1016/j.xphs.2017.06.007
       
  • Incomplete loading of SLS and FaSSIF micelles within the diffusion layers
           of dispersed drug particles during dissolution
    • Authors: Kendra Galipeau; Michael Socki, Adam Socia, Paul A. Harmon
      Abstract: Poorly water soluble drug candidates have been common in developmental pipelines over the last several decades. This has fueled considerable research around understanding how bile salt and model micelles can improve drug particle dissolution rates and human drug exposure levels. However, in the pharmaceutical context only a single mechanism of how micelles load solute has been assumed, that being the direct loading mechanism put forth by Cussler1 40 years ago. In this model micelles load at the particle surface and will be loaded to their equilibrium loading values.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-15
      DOI: 10.1016/j.xphs.2017.06.006
       
  • Influence of dissolution media and presence of alcohol on the in vitro
           performance of pharmaceutical products containing an insoluble drug
    • Authors: Valeria Friuli; Lauretta Maggi, Giovanna Bruni, Giorgio Musitelli, Ubaldo Conte
      Abstract: The purpose of this investigation is to determine how the dissolution media may influence the release rate of an insoluble drug in in-vitro conditions. Some oral dosage forms containing Ibuprofen, a molecule that shows pH-dependent solubility, are tested. They are evaluated in different media to simulate the gastrointestinal transit at paddle rotation speeds of 50 and 100 rpm. Moreover, the potential effect of different ethanol concentrations on drug release is tested. The dissolution profiles of the tablets show a similar behavior in water, pH 1.0 and phosphate buffer pH 4.5 where the two doses are not completely dissolved.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-14
      DOI: 10.1016/j.xphs.2017.06.001
       
  • Hot melt extrusion (HME) as solvent-free technique for a continuous
           manufacturing of drug-loaded mesoporous silica
    • Authors: Natalja Genina; Batol Hadi, Korbinian Löbmann
      Abstract: The aim of the study was to explore hot melt extrusion (HME) as a solvent-free drug loading technique for preparation of stable amorphous solid dispersions (ASD) using mesoporous silica (PSi). Ibuprofen (IBU) and carvedilol (CAR) were used as poorly soluble active pharmaceutical ingredients (APIs). Due to the high friction of a API: PSi mixture below the loading limit of the API, it was necessary to add the polymer Soluplus® (SOL) in order to enable the extrusion process. As a result the APIs distributed between the PSi and SOL phase after HME.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-08
      DOI: 10.1016/j.xphs.2017.05.039
       
  • Rifampin Stability and Solution Concentration Enhancement through
           Amorphous Solid Dispersion in Cellulose ω-Carboxyalkanoate Matrices
    • Authors: Hale Çiğdem Arca; Laura I. Mosquera-Giraldo, Junia M. Pereira, Nammalwar Sriranganathan, Lynne S. Taylor, Kevin J. Edgar
      Abstract: Tuberculosis (TB) is a deadly infectious disease; approximately 2 billion people are currently latently infected with the causative agent Mycobacterium tuberculosis. Approximately 8 million new active cases and 2 million deaths due to TB are recorded annually1. Rifampin (Rif) is a vital first line TB treatment drug. Its effectiveness is hampered by the high dose required (600 mg 1x/day) and by its moderate, variable bioavailability. These issues can be explained by Rif instability at gastric pH, limited solubility at neutral pH, polymorphism, and stimulation of its own metabolism.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-07
      DOI: 10.1016/j.xphs.2017.05.036
       
  • Automated Supersaturation Stability Assay to Differentiate Poorly Soluble
           Compounds in Drug Discovery
    • Authors: Suzanne M. Skolnik; Gina M. Geraci, Stephanie Dodd
      Abstract: Increasingly, in vitro assays evaluate a compound’s tendency to maintain supersaturation towards improving oral absorption. Throughput remains a challenge and only small sets of compounds are evaluated in reported studies. The present work describes an automated workflow and data analysis approach to determine supersaturation stability after 16 minutes. Eight increasing concentrations were targeted and supernatant concentration was measured following solvent-shift in FaSSIF. The effect of DMSO on both equilibrium solubility and on induced supersaturation was addressed, while the change in concentration was evaluated over time.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.025
       
  • Formulation Optimization of Freeze-Dried Long-Circulating Liposomes and
           In-Line Monitoring of the Freeze-Drying Process using an NIR Spectroscopy
           Tool
    • Authors: Bianca Sylvester; Alina Porfire, Pieter-Jan Van bockstal, Sebastian Porav, Marcela Achim, Thomas DE. Beer, Ioan Tomuță
      Abstract: The effect of lyoprotectant type and concentration on the stability of freeze-dried prednisolone sodium phosphate-loaded long-circulating liposomes (LCL-PLP) was investigated. Trehalose at a 5:1 carbohydrate to lipid molar ratio proved to be superior in maintaining the structural integrity and the permeability properties of the liposome bilayers, assuring the desired characteristics of the final product: a cake with a porous structure and easy to reconstitute, a similar size to the liposomes prior to freeze-drying, a high percent of encapsulated drug and a low residual moisture content.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.024
       
  • Amorphous solid dispersion of meloxicam enhanced oral absorption in rats
           with impaired gastric motility
    • Authors: Hiroki Suzuki; Keisuke Yakushiji, Saori Matsunaga, Yukinori Yamauchi, Yoshiki Seto, Hideyuki Sato, Satomi Onoue
      Abstract: Meloxicam (MEL) shows a slow onset of action in severe pain patients due to delayed gastric motility. This study aimed to develop an amorphous solid dispersion (ASD) of MEL to achieve rapid oral absorption in severe pain patients. ASD formulations of MEL with hydroxypropylmethylcellulose (ASD-MEL/HPMC) and polyacrylates and polymethacrylates (ASD-MEL/EUD) were prepared and physicochemically characterized. Oral absorption behavior of MEL samples was also clarified in both normal and propantheline (PPT)-pretreated rats with impaired gastric motility.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.023
       
  • Transformation of BCS Class I and III Drugs into Ionic Liquids and
           Lipophilic Salts For Enhanced Developability Using Lipid Formulations
    • Authors: Hywel D. Williams; Leigh Ford, Shea Lim, Sifei Han, John Baumann, Hannah Sullivan, David Vodak, Annabel Igonin, Hassan Benameur, Colin W. Pouton, Peter J. Scammells, Christopher J.H. Porter
      Abstract: Higher lipid solubility of lipophilic salt forms creates new product development opportunities for high-dose liquid-filled capsules. The purpose of this study was to determine if lipophilic salts of BCS Class I amlodipine and BCS Class III fexofenadine, ranitidine and metformin were better lipid formulation candidates than existing commercial salts. Lipophilic salts were prepared from lipophilic anions and commercial HCl or besylate salt forms, as verified by 1H NMR. Thermal properties were assessed by DSC and hot-stage microscopy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-23
      DOI: 10.1016/j.xphs.2017.05.019
       
  • Using potentiometric free drug sensors to determine the free concentration
           of ionisable drugs in colloidal systems
    • Authors: Thuy Tran; Anjan Chakraborty, Xi Xi, Hugo Bohets, Claus Cornett, Konstantin Tsinman, Thomas Rades, Anette Müllertz
      Abstract: The current study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions and emulsions and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) were selected as model drugs. Self-diffusion nuclear magnetic resonance (NMR) studies were performed and confirmed the entrapment of drugs in micelles in Brij 35 and sodium taurodeoxycholate (TDC)/phosphatidylcholine (PC) micellar solutions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-23
      DOI: 10.1016/j.xphs.2017.05.016
       
  • The Application of Modeling and Prediction to the Formation and Stability
           of Amorphous Solid Dispersions
    • Authors: Kevin DeBoyace; Peter Wildfong
      Abstract: Amorphous solid dispersion (ASD) formulation development is frequently difficult owing to the inherent physical instability of the amorphous form, and limited understanding of the physical and chemical interactions that translate to initial dispersion formation and long-term physical stability. Formulation development for ASDs has been historically accomplished through trial and error or experience with extant systems, however, rational selection of appropriate excipients is preferred to reduce time to market and decrease costs associated with development.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-04-04
      DOI: 10.1016/j.xphs.2017.03.029
       
  • Poor Quality and Counterfeit Drugs: a systematic assessment of prevalence
           and risks based on data published from 2007-2016
    • Authors: Andreas Koczwara; Jennifer Dressman
      First page: 2921
      Abstract: Counterfeit drugs can hurt patients and harm the pharmaceutical industry. In 2006, the International Medical Products Anti-Counterfeiting Taskforce expressed a need to generate more and better data to calculate a worldwide prevalence of counterfeiting. This review analyzes field test data that were published in the time-frame January 2007 to December 2016, were accessible via Pubmed, and which addressed the prevalence of counterfeit drugs.Based on the 41 studies identified, it is still not possible to make a reliable statement about the prevalence of counterfeit drugs due to the heterogeneity of the results.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-23
      DOI: 10.1016/j.xphs.2017.05.018
       
  • Biowaiver Monograph for Immediate Release Solid Oral Dosage Forms:
           Amoxicillin Trihydrate
    • Authors: Dhanusha Thambavita; Priyadarshani Galappatthy, Uthpali Mannapperuma, R.L. Jayakody, Rodrigo Cristofoletti, Bertil Abrahamsson, D.W. Groot, Peter Langguth, Mehul Mehta, Alan Parr, James E. Polli, Vinod P. Shah, Jennifer Dressman
      First page: 2930
      Abstract: Literature and experimental data relevant to waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing amoxicillin trihydrate are reviewed. Solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), therapeutic uses, therapeutic index, excipient interactions, as well as dissolution and BE/bioavailability (BA) studies were taken into consideration. Solubility and permeability studies indicate that amoxicillin doses up to 875mg belong to BCS class I, while 1000 mg belongs to BCS class II and doses above 1000mg belong to BCS class IV.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-05
      DOI: 10.1016/j.xphs.2017.04.068
       
  • Perspectives on Subcutaneous Route of Administration as an Immunogenicity
           Risk Factor for Therapeutic Proteins
    • Authors: Lora Hamuro; Grzegorz Kijanka, Francis Kinderman, Harald Kropshofer, De-xiu Bu, Monica Zepeda, Vibha Jawa
      First page: 2946
      Abstract: An increasing number of therapeutic proteins are being developed for delivery through the subcutaneous (SC) route of administration. Relative to intravenous (IV) administration, the SC route offers more convenience to patients, flexibility in dosing and potential to reduce health care costs. There is a perception that SC administration can pose a higher immunogenicity risk than IV administration for a given protein. To evaluate if there is a difference in therapeutic protein immunogenicity associated with administration routes, a more detailed understanding of the interactions with the immune system by each route is needed.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-30
      DOI: 10.1016/j.xphs.2017.05.030
       
  • Thermo-Optical Protein Characterization for Straightforward Preformulation
           Development
    • Authors: Randy Wanner; Dennis Breitsprecher, Stefan Duhr, Philipp Baaske, Gerhard Winter
      First page: 2955
      Abstract: The determination of protein unfolding and aggregation characteristics during preformulation is of major significance for the development of biopharmaceuticals. The aim of this study was to investigate the feasibility of a new immobilization- and label-free thermo-optical approach as an orthogonal method for material and time saving early formulation and drugability screenings. In the experimental setup used, changes in the intrinsic tryptophan fluorescence of the protein were measured during IR-laser induced heating of the samples.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-14
      DOI: 10.1016/j.xphs.2017.06.002
       
  • Protein adsorption to in-line filters of intravenous administration sets
    • Authors: Ahmed Besheer
      First page: 2959
      Abstract: Ensuring compatibility of administered therapeutic proteins with IV administration sets is an important regulatory requirement. A low dose-recovery during administration of low protein concentrations is among the commonly observed incompatibilities, and it is mainly due to adsorption to in-line filters. To better understand this phenomenon, we studied the adsorption of 4 different therapeutic proteins (2 IgG1s, 1 IgG4 and 1 Fc Fusion protein) diluted to 0.01 mg/mL in 5% glucose or 0.9% NaCl solutions to 8 in-line filters (5 positively charged and 3 neutral filters made of different polymers and by different suppliers).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-27
      DOI: 10.1016/j.xphs.2017.05.028
       
  • Friability testing as a new stress-stability assay for biopharmaceuticals
    • Authors: Tetsuo Torisu; Takahiro Maruno, Saki Yoneda, Yoshinori Hamaji, Shinya Honda, Tadayasu Ohkubo, Susumu Uchiyama
      First page: 2966
      Abstract: A cycle of dropping and shaking a vial containing antibody solution was reported to induce aggregation. In this study, antibody solutions in glass prefillable syringes with or without silicone oil lubrication were subjected to the combined stresses of dropping and shaking, using a friability testing apparatus. Larger numbers of subvisible particles were generated, regardless of silicone oil lubrication, upon combination stress exposure than that with shaking stress alone. Nucleation of antibody molecules upon perturbation by an impact of the dropping, and/or adsorption of antibody molecules to the syringe surface followed by film formation and antibody film desorption were considered key steps in the particle formation promoted by combination stress.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-08
      DOI: 10.1016/j.xphs.2017.05.035
       
  • Biophysical Characterization and Thermal Stability of Pneumococcal
           Histidine Triad Protein D (PhtD) in the presence of Zinc and Manganese
    • Authors: Salvador F. Ausar; Kavisha Jayasundara, Lamees Akawi, Cristopher Roque, Anthony Sheung, Jian Hu, Marina Kirkitadze, Nausheen Rahman
      First page: 2979
      Abstract: The Pneumococcal Histidine Triad Protein D (PhtD) is believed to play a central role in pneumococcal metal ion homeostasis and has been proposed as a promising vaccine candidate against pneumococcal disease. To investigate for potential stabilizers, a panel of physiologically relevant metals was screened using the thermal shift assay and it was found that only Zn2+ and Mn2+ were able to increase PhtD melting temperature. Differential Scanning Calorimetry (DSC) analysis revealed a sequential unfolding of PhtD and the presence of at least 3 independent folding domains that can be stabilized by Zn2+ and Mn2+.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-14
      DOI: 10.1016/j.xphs.2017.06.003
       
  • Influence of a Small Amount of Glycerol on the Trehalose Bioprotective
           Action Analyzed In-Situ During Freeze-Drying of Lyzozyme Formulations by
           Micro-Raman Spectroscopy
    • Authors: Tatiana Starciuc; Yannick Guinet, Laurent Paccou, Alain Hedoux
      First page: 2988
      Abstract: Micro-Raman spectroscopy gives the original opportunity to monitor simultaneously the operating process and the protein structure from in-situ investigations along the three stages of the freeze-drying (FD) process. This opportunity was used for determining how a small amount of glycerol enhances the bioprotective efficiency of trehalose during freeze-drying of lysozyme formulations. Three lysozyme formulations were analyzed: lysozyme dissolved in D2O (wt% 1:9), in Trehalose-D2O mixture (wt% 1:1:8) and in the Trehalose-Glycerol-D2O mixture (wt% 1:1:0.17:7.93).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-14
      DOI: 10.1016/j.xphs.2017.05.040
       
  • Crystal Structures and Vapour Induced Crystalline Transformation of 7 -
           ethyl - 10 - hydroxy Camptothecin Pseudopolymorphs
    • Authors: Lan Fang; Lei Wang, Changlin Yao, Shuang Song, Zexin Wu, Xutang Tao
      First page: 2998
      Abstract: Solvent-induced three frameworks (the monohydrate, methanol solvate and DMF solvate) of an anticancer drug, 7 - ethyl - 10 - hydroxy camptothecin (SN38) were constructed. The crystal structures of the three pseudopolymorphs were characterized by single crystal X-ray diffraction technique for the first time. Crystal structure analysis of all these polymorphs revealed that the monohydrate showed three-dimensional frameworks linked by hydrogen bonds. In the methanol solvate, the 1D molecular chains were linked by the methanol molecules through intermolecular hydrogen bonds to form a 2D sheet.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-03-24
      DOI: 10.1016/j.xphs.2017.03.020
       
  • Real-Time Analysis of Tenofovir Release Kinetics Using Quantitative
           Phosphorus (31P) Nuclear Magnetic Resonance Spectroscopy
    • Authors: Vivek Agrahari; Jianing Meng, Sudhaunshu S. Purohit, Nathan A. Oyler, Bi-Botti C. Youan
      First page: 3005
      Abstract: The dialysis method is classically used for drug separation before analysis, but, does not provide direct and real-time drug quantification and has limitations affecting the dialysis rate. In this study, a phosphorus nuclear magnetic resonance (31P-qNMR) method is developed for the real-time quantification of therapeutic molecules in vitro. The release kinetics of model drug tenofovir (TFV: anti-HIV microbicide) was analyzed in vaginal fluid simulant (VFS), semen fluid simulant (SFS), and human plasma (HP) from chitosan nanofibers (size ∼100-200nm) using the NMR (direct) method and compared with dialysis/UV-Vis (indirect) method.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-04-14
      DOI: 10.1016/j.xphs.2017.03.043
       
  • Melting Process of the Peritectic Mixture of Lidocaine and Ibuprofen
           Interpreted by Site Percolation Theory Model
    • Authors: Hikaru Kataoka; Yoshinori Sakaki, Kazushi Komatsu, Yohsuke Shimada, Satoru Goto
      First page: 3016
      Abstract: Eutectic mixtures are often used in the design and delivery of drugs. In this study, we examined the peritectic mixture of lidocaine (LDC) and ibuprofen (IBP) using differential scanning calorimetry, Raman spectroscopy, and microscopy. The obtained phase diagram shows that as the mixture is heated, first LDC melts at 293 K, then IBP dissolves in the liquefied LDC at 310 K, and finally all remaining crystals melt. In the 1H NMR spectra, the signals of the carboxyl group in IBP and amide or amine group in LDC shift to the low magnetic field in the IBP/LDC mixtures, because of the intermolecular interaction between these moieties.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-04-15
      DOI: 10.1016/j.xphs.2017.04.010
       
  • Effects of coating materials and processing conditions on flow enhancement
           of cohesive acetaminophen powders by high-shear processing with
           pharmaceutical lubricants
    • Authors: Guoguang Wei; Sharad Mangal, John Denman, Thomas Gengenbach, Kevin Lee Bonar, Rubayat Islam Khan, Li Qu, Tonglei Li, Qi (Tony) Zhou
      First page: 3022
      Abstract: This study has investigated the surface coating efficiency and powder flow improvement of a model cohesive acetaminophen powder by high shear processing with pharmaceutical lubricants via two common equipment, conical comil and high shear mixer. Effects of formulation and processing parameters on powder flow and surface coating coverage were evaluated. Both Carr’s index and shear cell data indicated that processing with the lubricants using comil or high shear mixer substantially improved the flow of the cohesive acetaminophen powder.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.020
       
  • Application of 1D and 2D solid-state NMR spectroscopy to the
           characterization of morphine, morphine hydrochloride and their hydrates
    • Authors: C.B. Romañuk; Y. Garro-Linck, M.S. Alves de Santana, R.H. Manzo, A.P. Ayala, G.A. Monti, A.K. Chattah, M.E. Olivera
      First page: 3033
      Abstract: The detailed knowledge of the solid forms of a drug is a key element in pharmaceutical development. Morphine, is an opiate alkaloidwidely used to treat severe acute and chronic pain. Much of the available information on its solid state dates from several decades ago. In order to obtain updated and reliable information1D and 2D solid-state NMR spectroscopy were used, and complemented with powder X-ray diffraction, FTIR and RAMAN spectroscopy and thermal analysis.13C CPMAS 1D spectra accomplish a complete identification of the related forms of morphine.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.021
       
  • Delivery of riboflavin-5’-monophosphate into the cornea: can liposomes
           provide any enhancement effects?
    • Authors: Neva Kandzija; Vitaliy V. Khutoryanskiy
      First page: 3041
      Abstract: Keratoconus is a progressive condition caused by the thinning of the cornea, which eventually deforms the front surface of the eye into a cone shape leading to ghosting, multiple images, glare and several other vision problems. Currently keratoconus is treated with UV-induced ribofiavin-mediated collagen cross-linking, which requires a physical removal of the corneal epithelium under topical anesthesia. This study reports the penetration of riboflavin (Rb) and its more water-soluble form, riboflavin-5’- monophosphate (RbP), into the bovine cornea ex vivo.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.022
       
  • A combinatorial statistical design approach to optimize the nanostructured
           cubosomal carrier system for oral delivery of ubidecarenone for management
           of doxorubicin induced cardiotoxicity: In Vitro–In Vivo investigations
    • Authors: Abdul Muheem; Faiyaz Shakeel, Musarrat H. Warsi, Gaurav K. Jain, Farhan J. Ahmad
      First page: 3050
      Abstract: Present work aims to optimize and characterize orally administered, ubidecarenone (UDC) loaded glycerylmonooleate (GCBMs) and phytantriol (PCBMs) based cubosomes (CBMs) for effective management of doxorubicin-induced cardiotoxicity and to enhance bioavailability of UDC. Formulations optimized using statistical hybrid-design approach exhibited particle size of 152.0 ± 1.78 nm and 248.8 ± 1.83 nm; polydispersity index (PDI) 0.183 ± 0.021 and 0.225 ± 0.018 with zeta potential of -26.8 ± 0.76 mV and -23.3 ± 0.22 mV and entrapment efficiency (% EE) of 92.3 ± 4.99% and 94.7 ± 5.67%, for GCBMs and PCBMs, respectively.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-25
      DOI: 10.1016/j.xphs.2017.05.026
       
  • Co-loaded nanoparticles of paclitaxel and piperlongumine for enhancing
           synergistic anti-tumor activities and reducing toxicity
    • Authors: Qi Liu; Di Zhao, Xiaojie Zhu, Huili Chen, Yue Yang, Jiaqiu Xu, Qing Zhang, Ali Fan, Ning Li, Chaorui Guo, Ying Kong, Yang Lu, Xijing Chen
      First page: 3066
      Abstract: The purpose of this study was to develop a nano-carrier system for co-delivery of paclitaxel (PTX) and piperlongumine (PL) and investigate the therapeutic potential of improving efficacy and reducing toxicity. PTX and PL were formulated into poly lactic-co-glycolic acid (PLGA) and D-α-tocopheryl polyethylene glycol succinate (TPGS) via organic solvent evaporation method. The average diameter was 117.1 ± 1.9 nm and the zeta potential was -43.25 ± 2.76 mV. PL facilitated the cellular uptake of PTX and the increased cytotoxicity was similarly displayed.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-25
      DOI: 10.1016/j.xphs.2017.05.027
       
  • Water-Soluble Combretastatin A4 Phosphate Orally Delivered via Composite
           Nanoparticles with Improved Inhibition Effect towards S180 Tumors
    • Authors: Yurun Shen; Liping Wu, Liyan Qiu
      First page: 3076
      Abstract: Combretastatin A4 phosphate (CA4P) is a novel vascular disrupting agent for cancer therapy. However, frequent dosing and negative patient compliance has been encountered over CA4P by injection administration due to its quite short-term action and acute side effects. Therefore, it is significant to develop an oral formulation of CA4P. We established a novel method to prepare CA4P-loaded nanoparticles (CA4P-NPs) for oral administration by combining methoxy poly(ethylene glycol)-b-polylactide (PELA) and poly(D,L-lactic-co-glycolic acid) (PLGA) polymers.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-14
      DOI: 10.1016/j.xphs.2017.05.031
       
  • Effect of grinding on the solid state stability and particle dissolution
           of acyclovir polymorphs
    • Authors: Federico Magnoni; Maria Rosa Gigliobianco, Dolores Vargas Peregrina, Roberta Censi, Piera Di Martino
      First page: 3084
      Abstract: The present work investigated the solid state change of four acyclovir polymorphs when ground at room temperature (Method A) and under cryo-grinding in the presence of liquid nitrogen (Method B). Modifications in particle size and shape (evaluated by scanning electron microscopy) and in the water content (evaluated by thermal analysis) were related to transitions at the solid state, as confirmed by X-ray powder diffractometry. Anhydrous Form I was stable under grinding by both methods A and B. The anhydrous Form II was stable during grinding under Method A, while it was progressively converted to the hydrate Form V during grinding under Method B.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-07
      DOI: 10.1016/j.xphs.2017.05.037
       
  • Conversion of Pregabalin to 4-Isobutylpyrrolidone-2
    • Authors: Amanda M. Drachnik; Harshita Kumari, Collin M. Mayhan, Drew A. Fowler, Wei G. Wycoff, Charles L. Barnes, John E. Adams, Carol A. Deakyne, Jerry L. Atwood
      First page: 3095
      Abstract: Solid state studies of C-butyl-resorcin[4]arene with pregabalin (Lyrica, Nervalin) in nitrobenzene yielded a cocrystal of C-butyl-resorcin[4]arene with 4-isobutylpyrrolidone-2. A combined experimental and quantum chemical investigation was implemented to further our understanding of the factors affecting the conversion process.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-04-15
      DOI: 10.1016/j.xphs.2017.03.044
       
  • Hexagonal liquid crystalline nanodispersions proven superiority for
           enhanced oral delivery of rosuvastatin: in-vitro characterization and
           in-vivo pharmacokinetic study
    • Authors: Mai Mahmoud Gabr; Sana Mohamed Mortada, Marwa Ahmed Sallam
      First page: 3103
      Abstract: This study aimed to explore the potential of tailoring the liquid crystalline structure for augmenting the oral absorption and biopharmaceutical performance of Rosuvastatin. Rosuvastatin-loaded liquid crystalline nanodispersions (LCNDs) were prepared via emulsification technique. The effect of incorporating oleic acid (OA) in various proportions in the lipid domain of the LCNDs was studied. The formulations were characterized for particle size, zeta potential, in-vitro release, ex-vivo intestinal permeation, in-vivo oral bioavailability and stability.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-04
      DOI: 10.1016/j.xphs.2017.04.060
       
  • Identification and evaluation of the minimum unit of a KALA peptide
           required for gene delivery and immune activation
    • Authors: Naoya Miura; Kota Tange, Yuta Nakai, Hideyoshi Harashima, Hidetaka Akita
      First page: 3113
      Abstract: The KALA peptide (WEAKLAKALAKALAKHLAKALAKALKA) is an amphiphilic peptide that forms an α-helical structure at physiological pH. We previously reported that, when a pDNA-encapsulating liposomal membrane is modified with the KALA peptide, transgene expression and immune activation are facilitated in bone marrow-derived dendritic cells (BMDCs). However, the minimum unit of the KALA peptide and the importance of its secondary structure for these activities are not completely known at this time. We herein report on the identification of the minimum unit of the KALA peptide (short-KALA) required for activity, as determined by the stepwise removal of “K-A-L-A” units.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-20
      DOI: 10.1016/j.xphs.2017.05.014
       
  • Self-assembled core–shell-type lipid–polymer hybrid nanoparticles:
           intracellular trafficking and relevance for oral absorption
    • Authors: Qiuxia Li; Dengning Xia, Jinsong Tao, Aijun Shen, Yuan He, Yong Gan, Chi Wang
      First page: 3120
      Abstract: Lipid–polymer hybrid nanoparticles (NPs) are advantageous for drug delivery. However, their intracellular trafficking mechanism and relevance for oral drug absorption are poorly understood. In this study, self-assembled core–shell lipid–polymer hybrid NPs made of PLGA and various lipids were developed to study their differing intracellular trafficking in intestinal epithelial cells, and their relevance for oral absorption of a model drug saquinavir (SQV). Our results demonstrated that the endocytosis and exocytosis of hybrid NPs could be changed by varying the kind of lipid.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-27
      DOI: 10.1016/j.xphs.2017.05.029
       
  • Paclitaxel Encapsulated in Halloysite Clay Nanotubes for Intestinal and
           Intracellular Delivery
    • Authors: R. Yendluri; Y. Lvov, M. DeVilliers, V. Vinokurov, E. Naumenko, E. Tarasova, R. Fakhrullin
      First page: 3131
      Abstract: Naturally formed halloysite tubules have a length of 1 μm length and lumens with a diameter of 12-15 nm which can be loaded with drugs. Halloysite’s biocompatibility allows for its safe delivering to cells at a concentration of up to 0.5 mg/mL. We encapsulated the anti-cancer drug paclitaxel in halloysite and evaluated the drug release kinetics in simulated gastric and intestinal conditions. To facilitate maximum drug release in intestinal tract, halloysite tubes were coated with the pH-responsive polymer poly(methacrylic acid-co-methyl methacrylate).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-06
      DOI: 10.1016/j.xphs.2017.05.034
       
  • Mechanistic analysis of human skin distribution and follicular targeting
           of adapalene loaded biodegradable nanospheres with an insight into
           hydrogel matrix influence, in-vitro skin irritation and in-vivo
           tolerability
    • Authors: Marwa Ahmed Sallam; M. Teresa Marín Boscá
      First page: 3140
      Abstract: This work aimed at the development of a biocompatible, non-oily nanomedicine for follicular delivery of adapalene (AD) ameliorating its irritation potential for convenient localized topical treatment of acne vulgaris. AD was efficiently incorporated into poly-Ԑ-caprolactone nanospheres (NS) with an encapsulation efficiency of (84.73± 1.52%), a particle size of (107.5± 8.19 nm), and zeta potential of -13.1 mV demonstrating a sustained release behavior. The AD-NS were embedded in either HPMC or hyaluronate gel (HA).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-08
      DOI: 10.1016/j.xphs.2017.05.038
       
  • The binary system of ibuprofen-nicotinamide under nanoscale confinement:
           from cocrystal to coamorphous state
    • Authors: Yanping Bi; Deli Xiao, Shuai Ren, Shuyan Bi, Jianzhu Wang, Fei Li
      First page: 3150
      Abstract: Coamorphous systems have gained success in stabilizing amorphous drugs and improving their solubility and dissolution. Here we proposed to confine a binary mixture of drug and coformer (CF) within nanopores to obtain a nano-confined coamorphous (NCA) system. For proving feasibility of this proposal, a poorly water-soluble drug (ibuprofen, IBP) and a frequently used pharmaceutical CF (nicotinamide, NIC) were loaded into nanopores of mesoporous silica microspheres (MSMs). The solid state of NCA system was characterized by differential scanning calorimetry, X-ray powder diffraction, infrared spectrum and solid state nuclear magnetic resonance.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-15
      DOI: 10.1016/j.xphs.2017.06.005
       
  • Effect of Temperature on the Kinetics of the Activation of Treosulfan and
           Hydrolytic Decomposition of Its Active Epoxy-Derivatives
    • Authors: Michał Romański; Jakub Mikołajewski, Franciszek k. Główka
      First page: 3156
      Abstract: Treosulfan (TREO) is a prodrug applied in treatment of ovarian cancer and a myeloablative conditioning prior to stem cell transplantation. A sequential activation of TREO to intermediate monoepoxide (S,S-EBDM) and then to (2S,3S)-1,2:3,4-diepoxybutane (S,S-DEB) involves a nonenzymatic intramolecular nucleophilic substitution. The aim of this study was to determine the effect of temperature on the rate constants (k) for the activation of TREO and the hydrolysis of its epoxy-derivatives in a phosphate buffer of pH 7.4 at an ionic strength of 0.16 – 0.17 M.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-06
      DOI: 10.1016/j.xphs.2017.05.033
       
  • Population approach to efavirenz therapy
    • Authors: Hélder Duarte; João Paulo Cruz, Natália Aniceto, Ana Clara Ribeiro, Ana Fernandes, Paulo Paixão, Francisco Antunes, José Morais
      First page: 3161
      Abstract: Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor commonly used as first line therapy in the treatment of human immunodeficiency virus, with a narrow therapeutic range and a high between-subject variability which can lead to central nervous system toxicity or therapeutic failure. To characterize the sources of variability and better predict EFV steady state plasma concentrations, a population pharmacokinetic model was developed form 96 HIV positive individuals, using a nonlinear mixed effect method with Monolix® software.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-13
      DOI: 10.1016/j.xphs.2017.06.004
       
  • On the use of group sequential study designs for the test of
           bioequivalence for complicated products
    • Authors: Rajesh Krishna; Wen-Lin Luo, Patrick J. Larson, Paul H. Fackler
      First page: 3167
      Abstract: A novel modeling approach together with a use of group sequential study design for a complicated triple fixed-dose combination was attempted. Probability of success (POS) was used for determining a weighted average power, where weight was based on available information such as data from previous pilot studies or literature. A simulation study was conducted that resulted in the development of the necessary sample size for the studies in addition to identifying a decision algorithm that was prospectively defined in the protocols.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-23
      DOI: 10.1016/j.xphs.2017.05.015
       
  • Pharmaceutical film coating catalogue for spectral-domain optical
           coherence tomography
    • Authors: Hungyen Lin; Yue Dong, Daniel Markl, Zijian Zhang, Yaochun Shen, J. Axel Zeitler
      First page: 3171
      Abstract: Optical coherence tomography (OCT) has recently been demonstrated to measure the film coating thickness of pharmaceutical tablets and pellets directly. The results enable the analysis of inter- and intra-tablet coating variability at an off-line and in-line setting. To date, only a few coating formulations have been tried and there is very little information on the applicability of OCT to other coatings. As it is well documented that optical methods including OCT are prone to scattering leading to limited penetration, some pharmaceutical coatings may not be measurable altogether.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-14
      DOI: 10.1016/j.xphs.2017.05.032
       
 
 
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