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Journal Cover Journal of Pharmaceutical Sciences
  [SJR: 0.984]   [H-I: 130]   [165 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0022-3549 - ISSN (Online) 1520-6017
   Published by Elsevier Homepage  [3177 journals]
  • Editorial Advisory Board
    • Citation: Journal of Pharmaceutical Sciences 107, 3 (2018)
      PubDate: 2018-03
      DOI: 10.1016/S0022-3549(18)30021-2
      Issue No: Vol. 107, No. 3 (2018)
  • Improving Prediction Of Metabolic Clearance Using Quantitative
           Extrapolation Of Results Obtained From Human Hepatic Mpcc Model And By
           Considering The Impact Of Albumin Binding
    • Authors: Franck Da-silva; Xavier Boulenc, Hélène Vermet, Pauline Compigne, Sabine Gerbal-Chaloin, Martine Daujat-Chavanieu, Sylvie Klieber, Patrick Poulin
      Abstract: The objective was to compare, with the same dataset, the predictive performance of three in vitro assays of hepatic clearance (CL), namely, micropatterned cocultures (MPCC) (also referring to HepatoPac®) and suspension as well as monolayer hepatocytes to define which assay is the most accurate. Furthermore, existing in vitro-to-in vivo extrapolation (IVIVE) methods were challenged to verify which method is the most predictive (i.e., direct scaling method without binding correction, conventional method based either on the unbound fraction in plasma (fup) according to the free drug hypothesis, or based on an fup value adjusted for the albumin (ALB)-facilitated hepatic uptake phenomenon).
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-03-07
      DOI: 10.1016/j.xphs.2018.03.001
  • Quantitative estimation of plasma free drug fraction in patients with
           varying degrees of hepatic impairment: a methodological evaluation
    • Authors: Guo-Fu Li; Guo Yu, Yanfei Li, Yi Zheng, Qing-Shan Zheng, Hartmut Derendorf
      Abstract: Quantitative prediction of unbound drug fraction (fu) is essential for scaling pharmacokinetics through physiologically-based approaches. However, few attempts have been made to evaluate the projection of fu values under pathological conditions. The primary objective of this study was to predict fu values (n=105) of 56 compounds with or without the information of predominant binding protein in patients with varying degrees of hepatic insufficiency by accounting for quantitative changes in molar concentrations of either the major binding protein or albumin plus alpha 1-acid glycoprotein (AAG) associated with differing levels of hepatic dysfunction.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-03-05
      DOI: 10.1016/j.xphs.2018.02.021
  • Effect of the Dispersion States of Azone in Hydro-alcoholic Gels on its
           Transdermal Permeation Enhancement Efficacy
    • Authors: Hui-lin Chen; Chen-chen Cai, Jun-yuan Ma, Mei-ling Yu, Mei-hui Zhao, Jian-bo Guo, Hui Xu
      Abstract: The objective of this study was to investigate the effect of dispersion states of azone in gels on the transdermal permeation of levamisole hydrochloride (LH). LH hydro-alcoholic gels containing azone of different dispersion states were prepared by varying the contents of azone and Tween80, and the in vitro transdermal permeation of LH across excised rat skin was evaluated. Depending on the content of azone, mixed solvents and solubilizer used, azone presented as dissolved molecules, solubilized in micelles, and fine or coarse emulsion droplets in gels.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-03-05
      DOI: 10.1016/j.xphs.2018.02.020
  • A conformationally-gated model of methadone and loperamide transport by
    • Authors: Morgan E. Gibbs; Laura A. Wilt, Kaitlyn V. Ledwitch, Arthur G. Roberts
      Abstract: P-glycoprotein (Pgp) is a multidrug resistance transporter that limits the penetration of a wide range of neurotherapeutics into the brain including opioids. The diphenylpropylamine opioids methadone and loperamide are structurally similar, but loperamide has about a 4-fold higher Pgp-mediated transport rate. In addition to these differences, they showed significant differences in their effects on Pgp-mediated ATP hydrolysis. The activation of Pgp-mediated ATP hydrolysis by methadone was monophasic, while loperamide activation of ATP hydrolysis was biphasic implying methadone has a single binding site and loperamide has two binding sites on Pgp.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-27
      DOI: 10.1016/j.xphs.2018.02.019
  • Fluorescence-Based High-Throughput Salt Screening
    • Authors: Kazue Kimura; Saho Onishi, Kei Moriyama
      Abstract: The present study reports a high-throughput screening method for the salt formation of amine-containing active pharmaceutical ingredients (APIs) based on fluorescence measurements. A free form amine API was alkynylated by a solid–vapor reaction using propargyl bromide, and a fluorescent compound was produced by a subsequent reaction using 9-azidomethylanthracene. In contrast, salts were inert to propargyl bromide; thus, no fluorescence was observed. Samples for salt screening were prepared by grinding haloperidol with various counter acids, and these mixtures were derivatized in a 96-well microplate to determine whether the salt formation had occurred between haloperidol and the counter acids.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-27
      DOI: 10.1016/j.xphs.2018.02.018
  • A newly identified impurity in Polysorbate 80, the long-chain ketone
           12-tricosanone, forms visible particles in a biopharmaceutical drug
    • Authors: Veronika Hampl; Xinghua Guo, Christian Ehrenstrasser, Martin Viertler, Lucy Rayner, Giusy Campanelli, Reinhard Schipflinger, Karine Thewes, Alessandra Cerreti, Stephan Boehm, Corinna Sonderegger
      Abstract: Visible particles linked to polysorbates used in biopharmaceutical drug products have been observed repeatedly in recent years as an industry-wide issue, with polysorbate degradation and insoluble degradation products, especially fatty acids and fatty acid esters, being suspected as root-cause. We have shown that the visible particles observed in a monoclonal antibody (mAB) drug product solution in vials after 18 months of long-term storage at 5 ± 3°C were neither linked to reduction in polysorbate (PS80) concentration nor to any known polysorbate degradation product, but consist of 12-tricosanone, an impurity present in the raw material PS80, not a degradation product.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-27
      DOI: 10.1016/j.xphs.2018.02.017
  • A bio-predictive in vitro comparison of oral locally-acting mesalazine
           formulations by a novel dissolution model for assessing intraluminal drug
           release in individual subjects
    • Authors: Frank Karkossa; Sandra Klein
      Abstract: Drug release and availability at the site of action are the major factors determining the clinical response for locally-acting gastrointestinal (GI) drug products. The present work focused on the prediction of site and extent of in vivo mesalazine release after oral administration to a variety of subjects using individualized in vitro drug release experiments. First, experiments mimicking GI passages in average adult subjects were performed. Then, results from a study screening fasted in vivo pH- and transit profiles in individual subjects were translated into a novel in vitro dissolution model enabling to mimic individual GI pH-profiles and transit times with physiologically relevant dissolution media.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-27
      DOI: 10.1016/j.xphs.2018.02.016
  • Effect of Crushing, Cutting into Half, or Grinding of Co-formulated
           Glecaprevir/Pibrentasvir Tablets on Pharmacokinetic Measurements in
           Healthy Subjects
    • Authors: Rajneet K. Oberoi; Weihan Zhao, Dilraj S. Sidhu, Rolando M. Viani, Roger Trinh, Wei Liu
      Abstract: Glecaprevir (GLE) and pibrentasvir (PIB) are direct-acting antivirals coformulated as a combination tablet for once-daily treatment of chronic hepatitis C virus infection. The objective of this study was to evaluate the effect of different methods of tablet manipulations – cutting in half, grinding into powder, or crushing– on the bioavailability of GLE and PIB relative to whole film-coated bilayer tablets. This was a Phase 1, single-dose, open-label, randomized, five-period, nonfasting, crossover study in 25 healthy adult male and female subjects.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-21
      DOI: 10.1016/j.xphs.2018.02.015
  • Improved Stability of TB Drug Fixed Dose Combination Using
           Isoniazid-Caffeic acid and Vanillic acid Cocrystal
    • Authors: Battini Swapna; M.K.Chaitanya Mannava, Ashwini Nangia
      Abstract: The classic FDC of four TB drugs, namely Rifampicin (RIF), Isoniazid (INH), Pyrazinamide (PZA) and Ethambutol Dihydrochloride (EDH) has the twin issues of physical stability and rifampicin cross-reaction in the 4FDC. The major reason for these quality issues is the interaction between RIF and INH to yield isonicotinyl hydrazone (HYD) in drug tablets. Pharmaceutical cocrystals of INH with caffeic acid (PZA + EDH + RIF + INH-CFA cocrystal) and vanillic acid (PZA + EDH + RIF + INH-VLA cocrystal) are able to stabilize the FDC formulation compared to the reference batch (PZA + EDH + RIF + INH).
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-17
      DOI: 10.1016/j.xphs.2018.02.014
  • Water Activity and its Significance in Topical Dosage Forms
    • Authors: Muralikrishnan Angamuthu; Vijay Kumar Shankar, S.Narasimha Murthy
      Abstract: Unique properties of thermodynamic activity of solvents in topical semisolids and its effects on in vitro product performance has not been fully understood. Mechanistic investigation was undertaken to demonstrate the significance of thermodynamic potential of solvents [water activity (aw) or solvent activity (as)] on in vitro performance of model topical formulations. Drug transport across synthetic membranes was found to decrease with decreasing water activity of formulations. Similarly, in vitro permeation of model permeant (caffeine) across porcine epidermis was found to decrease with decreasing water activity of formulations.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-17
      DOI: 10.1016/j.xphs.2018.02.013
  • Labrasol® and salts of medium chain fatty acids can be combined in low
           concentrations to increase the permeability of a macromolecule marker
           across isolated rat intestinal mucosae
    • Authors: Joanne Heade; Sam Maher, Sinead B. Bleiel, David J. Brayden
      Abstract: In addition to their solubilising properties, excipients used in lipid-based formulations (LBFs) can improve intestinal permeability of macromolecules. We determined whether ad-mixing of medium chain fatty acid (MCFA) permeation enhancers (PEs) with a lipoidal excipient (Labrasol®) could potentiate trans-epithelial flux of a poorly permeable macromolecule (FITC-dextran 4 kDa, FD4) across rat intestinal mucosae mounted in Ussing chambers. Low concentrations of sodium caprate (C10), sodium undecylenate (C11:1), or sodium laurate (C12) combined with Labrasol® increased the Papp of FD4 to values typically seen with higher concentrations of MCFAs or Labrasol® alone.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-17
      DOI: 10.1016/j.xphs.2018.02.012
  • Rapidly Dissolving Microneedle Patches for Transdermal Iron Replenishment
    • Authors: A. Maurya; H.N. Shivakumar, S. Honnavar, M. Salwa, S.N. Murthy
      Abstract: The prevalence of Iron Deficiency Anemia (IDA) is predominant in women and children especially in developing countries. The disorder affects cognitive functions and physical activity. While oral iron supplementation and parenteral therapy remains the preferred choice of treatment, gastric side effects and risk of iron overload decreases adherence to therapy. Transdermal route is an established approach which circumvents the side-effects associated with conventional therapy. In this project, an attempt was made to investigate the use of rapidly dissolving microneedles loaded with Ferric pyrophosphate (FPP) as a potential therapeutic approach for management of IDA.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-17
      DOI: 10.1016/j.xphs.2018.02.011
  • Inhibition of Organic Anion Transporting Polypeptide 1B1 and 1B3 by
           Betulinic Acid: Effects of Pre-incubation and Albumin in the Media
    • Authors: Yunseok Oh; Yoo-Seong Jeong, Min-Soo Kim, Jee Sun Min, Gongmi Ryoo, Ji Eun Park, Yearin Jun, Yoo-Kyung Song, Se-Eun Chun, Songhee Han, Soo Kyung Bae, Suk-Jae Chung, Wooin Lee
      Abstract: Betulinic acid (BA), a plant-derived pentacyclic triterpenoid, may interact with the members of the organic anion transporting polypeptide 1B subfamily. Here, we investigated the interactions of BA and its analogs with OATP1B1/3 and rat Oatp1b2 in vitro and in vivo. BA inhibited the activity of OATP1B1/3 and rat Oatp1b2 in vitro. Systemic exposure of atorvastatin was substantially altered with the intravenous co-administration of BA (20 mg/kg). Pre-incubation (incubation with inhibitors, followed by washout) with BA led to a sustained inhibition of OATP1B3, which recovered rapidly in the media containing 10% fetal bovine serum.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-17
      DOI: 10.1016/j.xphs.2018.02.010
  • An Unexpected Degradation Pathway of a 1,2,4-Triazolo[4,3-a]pyridine
           Derivative: The Formation of Two Cationic Pseudodimers of an
           11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Drug Candidate in a
           Stressed Capsule Formulation
    • Authors: Yande Huang; Qinggang Wang, Yongmei Wu
      Abstract: Degradation of an active pharmaceutical ingredient (API), a 2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol hydrochloride salt, was observed in a capsule formulation stressed at 50°C or 40°C/75% relative humidity conditions for one month. Two unknown degradants were identified as cationic pseudodimers of the API via accurate mass liquid chromatography-mass spectrometry and one- and two-dimensional NMR analyses. A plausible degradation pathway of the API was postulated which led to the identification of two key N-oxide degradants in the stressed capsule formulation at trace levels.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-17
      DOI: 10.1016/j.xphs.2018.02.009
  • Antisolvent recrystallization strategy to screen appropriate carriers to
           stabilize filgotinib amorphous solid dispersions
    • Authors: Fuzheng Ren; Hanjing Sun, Lin Cui, Yike Si, Ning Chen, Guobin Ren, Qiufang Jing
      Abstract: Drugs in amorphous solid dispersions (ASDs) are highly dispersed in hydrophilic polymeric carriers, which also help to restrain recrystallization and stabilize the ASDs. In this study, microscopic observation after antisolvent recrystallization was developed as a rapid screening method to select appropriate polymers for the initial design filgotinib (FTN) ASDs. Using solvent evaporation, FTN ASDs with the polymers were prepared, and accelerated experimentation validated this screening method. Fourier-transform infrared spectroscopy, Raman scattering, and nuclear magnetic resonance revealed hydrogen-bonding formation in the drug-polymer binary system, which was critical for ASDs stabilization.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-15
      DOI: 10.1016/j.xphs.2018.02.008
  • Development of adjuvanted solid fat nanoemulsions for pulmonary hepatitis
           b vaccination
    • Authors: Sunita Minz; Ravi Shankar Pandey
      Abstract: Pulmonary vaccination is one of the most promising routes for immunization owing to its non-invasive nature and induction of strong mucosal immunity and systemic response. In the present study, recombinant hepatitis B surface antigen loaded solid fat nanoemulsions (SFNs) as carrier system and monophosphoryl lipid A (MPLA) as an adjuvant-carrier system was prepared and evaluated as multi adjuvanted vaccine system for deep pulmonary vaccination. Deposition and clearance from the deep lung of rats were determined by gamma scintigraphy.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-15
      DOI: 10.1016/j.xphs.2018.02.007
  • The Synergetic Effects of Non-polar and Polar Protic Solvents on the
           Properties of Felodipine and Soluplus in Solutions, Casting Films and
           Spray Dried Solid Dispersions
    • Authors: Yuqi Chen; Wencong Huang, Jiali Chen, Hanning Wang, Shujuan Zhang, Subin Xiong
      Abstract: The aim was to explore the effects of non-polar and polar protic solvents composed of dichloromethane (DCM) and ethanol (EtOH) on the properties of felodipine (FLDP) and Soluplus in solutions, casting films and spray dried drug-rich or polymer-rich solid dispersions (SDs). Measurement of intrinsic viscosity and solubility indicated that FLDP and Soluplus were miscible. EtOH-DCM ranging from 20:80 to 50:50 induced the strongest molecular interactions for FLDP-Soluplus-solvents systems. Accordingly, the casting films and spray dried powders of FLDP and Soluplus were prepared using pure EtOH or DCM and their mixtures as solvents.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-15
      DOI: 10.1016/j.xphs.2018.02.006
  • Unusual Self-Assembly of the Recombinant Chlamydia trachomatis Major Outer
           Membrane Protein (MOMP)-based Fusion Antigen CTH522 into Protein
    • Authors: Fabrice Rose; Kasper Karlsen, Pernille Rønde Jensen, Rasmus Uffe Jakobsen, Grith Krøyer Wood, Kasper Dyrberg Rand, Helene Godiksen, Peter Andersen, Frank Follmann, Camilla Foged
      Abstract: Sexually transmitted Chlamydia trachomatis (Ct) infects more than 100 million people annually, and untreated chlamydia infections can cause severe complications. Therefore, there is an urgent need for a chlamydia vaccine. The Ct major outer membrane protein (MOMP) is highly immunogenic but is a challenging vaccine candidate by being an integral membrane protein, and the immunogenicity depends on a correctly folded structure. We investigated the biophysical properties of the recombinant MOMP-based fusion antigen CTH522, which is tested in early human clinical trials.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-13
      DOI: 10.1016/j.xphs.2018.02.005
  • In Vitro-In Vivo Evaluation of an Oral Ghost Drug Delivery Device for the
           Delivery of Salmon Calcitonin
    • Authors: Angus R. Hibbins; Mershen Govender, Sunaina Indermun, Pradeep Kumar, Lisa C. du Toit, Yahya E. Choonara, Viness Pillay
      Abstract: An orally administered site-specific Oral Ghost Drug Delivery (OGDD) Device was developed and evaluated for the administration of salmon calcitonin. In vitro drug release studies have been undertaken using biorelevant media as well as aspirated gastrointestinal fluid from a Large White pig in addition to characterization of a formulated trimethyl chitosan blend formulated and prepared into a loaded mini-pellet system. In vivo drug release analysis in a Large White pig model has further been undertaken on the OGDD device and a commercial intramuscular injection to ascertain the release properties of the OGDD device in an animal model in comparison with the currently used treatment option for the administration of salmon calcitonin.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-13
      DOI: 10.1016/j.xphs.2018.02.004
  • Synthesis of a glibenclamide cocrystal: full spectroscopic and thermal
    • Authors: Silvério Ferreira Silva Filho; Andreia Cardoso Pereira, Jorge M.G. Sarraguça, Mafalda C. Sarraguça, João Lopes, Pedro Freitas Filho, Adenilson Oliveira dos Santos, Paulo Roberto da Silva Ribeiro
      Abstract: A cocrystal of glibenclamide (GLB), an antidiabetic drug classified as type II compound according to the Biopharmaceutics Classification System (BCS), has been synthesised using tromethamine (TRIS) as coformer in 1:1 molar ratio, by slow solvent evaporation cocrystalization. The cocrystal obtained was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Raman, mid infrared (MIR), and near-infrared (NIR) spectroscopy. The results consistently show the formation of a cocrystal between API and conformer with the synthons corresponding to hydrogen bonding between hydrogen in amines of tromethamine and carbonyl and sulfonyl groups in glibenclamide.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-09
      DOI: 10.1016/j.xphs.2018.01.029
  • Application of the Quality by Design Approach to the Freezing Step of
           Freeze-Drying: Building the Design Space
    • Authors: Andrea Arsiccio; Roberto Pisano
      Abstract: The present work shows a rational method for the development of the freezing step of a freeze-drying cycle. The current approach to the selection of freezing conditions is still empirical and non-systematic, thus resulting in poor robustness of control strategy. The final aim of this work is to fill this gap, describing a rational procedure, based on mathematical modelling, for properly choosing the freezing conditions. Mechanistic models are used for the prediction of temperature profiles during freezing and dimension of ice crystals being formed.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-09
      DOI: 10.1016/j.xphs.2018.02.003
  • ‘Product on Stopper’ in a Lyophilized Drug Product: Cosmetic Defect or
           a Product Quality Concern'
    • Authors: Shyam B. Mehta; Shouvik Roy, Han-Chang (Cathy) Yang
      Abstract: During manufacturing of a lyophilized drug product, operator errors in product handling during loading of product filled vials onto the lyophilizer can lead to a seemingly cosmetic defect which can impact certain critical quality attributes of finished product. In this study, filling of a formulated monoclonal antibody in vials was performed using a peristaltic pump filling unit and subsequently the product was lyophilized. Post lyophilization, upon visual inspection, around 40% of vials had cosmetic defect with residual product around stopper of the vial and were categorized as ‘product on stopper’ vials while remaining 60% vials with no cosmetic defect were called ‘acceptable vials’.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-09
      DOI: 10.1016/j.xphs.2018.02.001
  • In-vitro evaluation of optimal inhalation flow patterns for commercial dry
           powder inhalers and pressurized metered dose inhalers with human
           inhalation flow pattern simulator
    • Authors: Daiki Hira; Tomoyuki Okuda, Ayano Mizutani, Nao Tomida, Hirokazu Okamoto
      Abstract: This study is aimed at developing a novel analytical method to identify optimal inhalation flow patterns for commercial dry powder inhalers (DPIs) and pressurized metered dose inhalers (pMDIs). As typical commercial DPI and pMDI, Pulmicort® Turbuhaler® and Sultanol® Inhaler were evaluated by an in-vitro inhalation performance testing system with a flow pattern simulator. An 8-stage Andersen cascade impactor (ACI) or twin stage liquid impinger (TSLI) was applied to determine the inhalation performance.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-08
      DOI: 10.1016/j.xphs.2018.02.002
  • Editorial Invitation to Become a Reviewer for the Journal of
           Pharmaceutical Sciences
    • Authors: Ronald T. Borchardt
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-06
      DOI: 10.1016/j.xphs.2018.01.028
  • Development of Stabilizing Formulations of a Trivalent Inactivated
           Poliovirus Vaccine in a Dried State for Delivery in the NanopatchTM
           Microprojection Array
    • Authors: Ying Wan; John M. Hickey, Christopher Bird, Katey Witham, Paul Fahey, Angus Forster, Sangeeta B. Joshi, David B. Volkin
      Abstract: The worldwide switch to inactivated polio vaccines (IPV) is a key component of the overall strategy to achieve and maintain global polio eradication. To this end, new IPV vaccine delivery systems may enhance patient convenience and compliance. In this work, we examine NanopatchTM (a solid, polymer micro-projection array) which offers potential advantages over standard needle/syringe administration including intradermal delivery and reduced antigen doses. Using trivalent IPV (tIPV) and a purpose-built evaporative dry-down system, candidate tIPV formulations were developed to stabilize tIPV during the drying process and upon storage.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.027
  • Folate conjugated Superoxide Dismutase adsorbed over antioxidant mimicking
           nanomatrix frameworks for treatment of Rheumatoid Arthritis
    • Authors: Shikha Srivastava; Deependra Singh, Manju R. Singh
      Abstract: Rheumatoid arthritis (RA) is an autoimmune disease occurring in larger population, characterized by synovial inflammation followed by destruction of joint. Major concerned factor for cause of Rheumatoid arthritis (RA) has been related to oxidative stress due to environmental toxicity and immune imbalance. Reactive oxygen species (ROS) generated from macrophages commune series of oxidation at cellular and genetic level and leads to generation of inflammatory cytokines for provoking inflammation in RA.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.026
  • Solubility Determination of APIs which have been recently added to the
           List of Essential Medicines (EML) in the context of the BCS-Biowaiver
    • Authors: Gerlinde F. Plöger; Martin A. Hofsäss, Jennifer B. Dressman
      Abstract: Since the publication of Lindenberg et al., which classified orally administered active pharmaceutical ingredients (APIs) on the 2004 Essential Medicines List (EML) of the World Health Organization (WHO) according to the Biopharmaceutics Classification System (BCS), various APIs have been added to the EML. In this work, BCS classifications for 16 of the orally administered APIs which were added to the EML after 2004 were determined. In order to establish a reliable solubility classification for all these compounds, a miniaturized shake-flask method was introduced.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.025
  • The preparation and physico-chemical characterization of aluminum
           hydroxide/TLR7a, a novel vaccine adjuvant comprising a small molecule
           adsorbed to aluminum hydroxide
    • Authors: Padma Malyala; Donatello Laera, Simona Cianetti, Simone Bufali, Marianna Aggravi, Elvira Ianni, Casey Judge, Gillis Otten, Manmohan Singh, Derek T. O’ Hagan
      Abstract: Adjuvants are necessary to enable vaccine development against a significant number of challenging pathogens for which effective vaccines are not available [1]. We engineered a novel small-molecule immune potentiator (SMIP), a benzonaphthyridine agonist targeting toll-like receptor 7 (TLR7), as a vaccine adjuvant. TLR7 agonist (TLR7a) was engineered to be adsorbed onto aluminum hydroxide (AlOH), and the resulting AlOH/TLR7a was evaluated as a vaccine adjuvant [2-6]. AlOH/TLR7a exploits the flexibility of AlOH formulations, has an application in many vaccine candidates, and induced good efficacy and safety profiles against all tested antigens (bacterial- and viral-derived protein antigens, toxoids, glycoconjugates, etc.) in many animal models, including non-human primates [7].
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.024
  • The safety and tolerability of topically delivered kynurenic acid in
           humans. A Phase 1 Randomized Double-Blind Clinical Trial
    • Authors: A. Papp; R. Hartwell, M. Evans, A. Ghahary
      Abstract: Scarring is a consequence of biological tissue repair following trauma. Currently there are no generally agreed ways to prevent scarring. Recently, kynurenic acid has shown to be a potent modulator of extracellular matrix deposition and remodeling. Kynurenic acid can reduce matrix deposition and other fundamental characteristics of fibrosis in vitro and in vivo. Specifically, kynurenic acid has shown to increase MMP-1 activity and subsequently reduce collagen deposition in a rabbit ear scar model.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.023
  • Editorial
    • Authors: Ronald T. Borchardt
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.022
  • Sweeping of adsorbed therapeutic protein on prefillable syringes promotes
           micron aggregate generation
    • Authors: Takahiro Maruno; Hiroki Watanabe, Saki Yoneda, Takayuki Uchihashi, Satoru Adachi, Kunihito Arai, Taichi Sawaguchi, Susumu Uchiyama
      Abstract: This study evaluated how differences in the surface properties of prefillable syringe (PFS) barrels and in-solution sampling methods affect micron aggregates and protein adsorption levels. Three syringe types [glass barrel with silicone oil coating (GLS/so+), glass barrel without silicone oil coating (GLS/so−) and cyclo-olefin polymer (COP) barrel syringes] were tested with three therapeutic proteins (adalimumab, etanercept, and infliximab) using two sampling methods (aspiration or ejection). After quiescent incubation, solutions sampled by aspiration exhibited no significant change in micron aggregate concentration in any syringes, whereas those sample by ejection exhibited increased micron aggregates in both GLS syringe types.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.021
  • “Structure Determination and Characterization of a Family of Primary
           Alcohol Solvates”
    • Authors: Kalyan V. Vasudevan; Matthew L. Peterson
      Abstract: We report the preparation and structural characterization of a family of primary alcohol solvates of a small molecule hydrochloride salt. The structures of the solvates are probed by powder and single crystal X-ray diffraction and the compounds were additionally characterized by polarized light microscopy, thermogravimetric analysis and dynamic scanning calorimetry. A comparison of the lattices of each compound is also provided. The results demonstrate the existence of a common solvating channel and highlight the importance of understanding the form landscape early in the development process.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.020
  • D-Optimal Design in the Development of Rheologically Improved In Situ
           Forming Ophthalmic Gel
    • Authors: Iva Krtalić; Senka Radošević, Anita Hafner, Mario Grassi, Mirta Nenadić, Biserka Cetina-Čižmek, Jelena Filipović-Grčić, Ivan Pepić, Jasmina Lovrić
      Abstract: In situ forming ophthalmic gels need to be fine-tuned considering all the biopharmaceutical challenges of the front of the eye in order to increase drug residence time at the application site resulting in its improved bioavailability and efficacy. The aim of this study was to develop in situ forming ophthalmic poloxamer P407/ poloxamer P188/chitosan gel fine-tuned in terms of polymer content, temperature of gelation and viscosity. Minimizing the total polymer content while retaining the advantageous rheological properties has been achieved by means of D-optimal statistical design.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-05
      DOI: 10.1016/j.xphs.2018.01.019
  • Structure-Function Relationships for Recombinant Erythropoietins: A Case
           Study From a Proposed Manufacturing Change With Implications for
           Erythropoietin Biosimilar Study Designs
    • Authors: Gustavo Grampp; Patricia L. McElroy, Gary Camblin, Allan Pollock
      Abstract: Comparability studies used to assess a proposed manufacturing change for a biological product include sensitive analytical studies to confirm there are no significant differences in structural or functional attributes that may contribute to clinically meaningful changes in efficacy or safety. When a proposed change is relatively complex or when clinically relevant differences between the product before and after the change cannot be ruled out based on analytical studies, nonclinical and clinical bridging studies are generally required to confirm overall comparability.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-04
      DOI: 10.1016/j.xphs.2018.01.018
  • Understanding the increased aggregation propensity of a light exposed IgG1
           mAb using hydrogen exchange mass spectrometry, biophysical
           characterization, and structural analysis
    • Authors: Rupesh Bommana; Qing Chai, Christian Schöneich, William F. Weiss, Ranajoy Majumdar
      Abstract: This work compares the conformational stability, backbone flexibility, and aggregation propensity of monomer and dimer fractions of an IgG1 monoclonal antibody (mAb) generated upon UVA light exposure for up to 72 hours collected by preparative size-exclusion chromatography (SEC), compared to unstressed control. UVA light exposure induced covalent aggregation, and fragmentation as measured by SEC, sodium dodecyl sulfate polyacrylamide gel electrophoresis and extensive oxidation of specific methionine residues (Met 257, Met 433, and Met 109) in both size fractions identified by reverse phase chromatography coupled to mass spectrometry.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-04
      DOI: 10.1016/j.xphs.2018.01.017
  • Investigation of ethylene oxide-co-propylene oxide for dissolution
           enhancement of hot-melt extruded solid dispersions
    • Authors: Dean Hurley; Catherine B. Potter, Gavin M. Walker, Clement L. Higginbotham
      Abstract: The optimal design of amorphous solid dispersion (ASD) formulations requires the use of excipients to maintain supersaturation and improve physical stability to ensure shelf-life stability and better absorption during intestinal transit, respectively. Blends of excipients (surfactants and polymers) are often used within pharmaceutical products to improve the oral delivery of BCS class II drugs. Therefore, in this study, a dissolution enhancer, poloxamer 407 (P407), was investigated to determine its effect on the dissolution properties and on the amorphous nature of the API contained in the formulation.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-03
      DOI: 10.1016/j.xphs.2018.01.016
  • Flow microscopy imaging is sensitive to characteristics of subvisible
           particles in peginesatide formulations associated with severe adverse
    • Authors: Austin L. Daniels; Theodore W. Randolph
      Abstract: The presence of subvisible particles in formulations of therapeutic proteins is a risk factor for adverse immune responses. Although the immunogenic potential of particulate contaminants likely depends on particle structural characteristics (e.g., composition, size, and shape), exact structure-immunogenicity relationships are unknown. Images recorded using flow imaging microscopy reflect information about particle morphology, but flow microscopy is typically used to determine only particle size distributions, neglecting information on particle morphological features that may be immunologically relevant.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-03
      DOI: 10.1016/j.xphs.2018.01.015
  • Influence of niobium pentoxide particulates on the properties of
           brushite/gelatin/alginate membranes
    • Authors: Hanan H. Beherei; Abdallah A. Shaltout, Mostafa Mobrouk, Nayera A.M. Abdelwahed, Diganta B. Das
      Abstract: Novel non-porous membranes were prepared by impregnating of brushite and niobium pentoxide (Nb2O5) into a gelatin/alginate matrix. The physicochemical properties, morphology and mechanical properties of the prepared membranes were characterized using XRD, FTIR, SEM, TEM and universal testing machine, respectively. Swelling ability of the prepared membranes was determined in distilled water. The surfaces of the membranes were characterized by means of FTIR and SEM coupled with EDX after submersion in simulated body fluid (SBF) up to 15 days.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-03
      DOI: 10.1016/j.xphs.2018.01.014
  • Measurement of Average Aggregate Density by Sedimentation and Brownian
           Motion Analysis
    • Authors: Richard E. Cavicchi; Jason King, Dean C. Ripple
      Abstract: The spatially averaged density of protein aggregates is an important parameter that can be used to relate size distributions measured by orthogonal methods, to characterize protein particles, and perhaps to estimate the amount of protein in aggregate form in a sample. We obtained a series of images of protein aggregates exhibiting Brownian diffusion while settling under the influence of gravity in a sealed capillary. The aggregates were formed by stir-stressing a monoclonal antibody (NISTmAb). Image processing yielded particle tracks, which were then examined to determine settling velocity and hydrodynamic diameter down to 1 μm based on mean square displacement (MSD) analysis.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-02-03
      DOI: 10.1016/j.xphs.2018.01.013
  • Editorial
    • Authors: Ronald T. Borchardt
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-15
      DOI: 10.1016/j.xphs.2018.01.012
  • Inhibition of CYP3A by antimalarial piperaquine and its metabolites in
           human liver microsomes with IVIV extrapolation
    • Authors: Mohd Yusmaidie Aziz; Kurt-Jürgen Hoffmann, Michael Ashton
      Abstract: The potential of the antimalarial piperaquine and its metabolites to inhibit CYP3A was investigated in pooled human liver microsomes. CYP3A activity was measured by LC-MS/MS as the rate of 1′-hydroxymidazolam formation. Piperaquine was found to be a reversible, potent inhibitor of CYP3A with the following parameter estimates (%CV): IC50 = 0.76 μM (29), Ki = 0.68 μM (29). In addition, piperaquine acted as a time-dependent inhibitor (TDI) with IC50 declining to 0.32 μM (28) during 30 min pre-incubation.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-15
      DOI: 10.1016/j.xphs.2018.01.009
  • Quantitative Monitoring the Anti-Solvent Crystallization and Storage
           Process for Nandrolone by Near-Infrared Spectroscopy
    • Authors: Xia Zeng; Xinnuo Xiong, Hongqin Yang, Bin Tang, Qiaohong Du, Quan Hou, Zili Suo, Hui Li
      Abstract: A novel hydrate (SH2O) of nandrolone (NT) was prepared by anti-solvent methods. The crystallization processes with two schemes (A and B) were monitored by in-line near-infrared (NIR) spectroscopy. The amounts of SH2O in powder samples obtained by the anti-solvent crystallization and storage process were quantified by NIR combined with chemometrics methods. In-line NIR spectra from 4500 to 8000 cm-1 were chosen to capture physicochemical changes during the whole crystallization process. The combination of the principal component (PCA) results with offline characterization (scanning electron microscopy, powder x-ray diffraction, NIR) data showed that both schemes yielded high purity SH2O products, but the crystallization speed of Scheme B was significantly accelerated.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-12
      DOI: 10.1016/j.xphs.2018.01.011
  • A Small-Scale Process for Predicting Donnan and Volume Exclusion Effects
           During UF/DF Process Development
    • Authors: Jeff Abel; Andrew Kosky, Nicole Ball, Haley Bacon, Rahul Kaushik, Gerd R. Kleemann
      Abstract: Achieving the desired final protein formulation using Ultrafiltration/Diafiltration (UF/DF) operations is an essential component of many protein purification processes. It is well documented that differences in the excipient and buffer concentrations exist between the diafiltration and retentate solutions when they have achieved equilibrium. Several publications have proposed ways to calculate these differences. However, the accuracy of these methods has been limited by the use of an estimated protein charge value.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-12
      DOI: 10.1016/j.xphs.2018.01.010
  • Antithrombin III Binding Site Analysis of Low Molecular Weight Heparin
    • Authors: Yin Chen; Jing Zhao, Yanlei Yu, Xinyue Liu, Lei Lin, Fuming Zhang, Robert J. Linhardt
      Abstract: Low molecular weight heparins (LMWHs) are widely used as clinical anticoagulant drugs. LMWHs are heterogeneous and highly negatively charged glycans prepared by chemical or enzymatic depolymerization of unfractionated heparin. The detailed structural analysis of a LMWH is essential for the drug quality control. In this study, a LMWH, enoxaparin sodium (a generic version of Lovenox) was separated to different molecular weights fractions by a Superdex peptide column. The disaccharide compositions, 3-O-sulfo group containing tetrasaccharides composition, and antithrombin III binding affinity of the fractions from this LMWH were analyzed.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-12
      DOI: 10.1016/j.xphs.2018.01.008
  • Development of Orally Applicable, Combinatorial Drug Loaded Nanoparticles
           for the Treatment of Fibrosarcoma
    • Authors: Gulen Melike Demirbolat; Levent Altintas, Sukran Yilmaz, Ismail Tuncer Degim
      Abstract: Nanoparticulate systems have been receiving a significant attention especially for the treatment of cancer but one of the main hurdles is to produce these developed and high tech nanosystems in large quantities. Anticancer drug formulations are generally designed for parenteral administrations but oral administration is still the most convenient route. In this study, orally applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared using Nano Spray Dryer. It is possible to produce these NPs in large quantities by simply increasing the processing time using the machine without changing any parameter.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-12
      DOI: 10.1016/j.xphs.2018.01.006
  • Challenges and opportunities for the subcutaneous delivery of therapeutic
    • Authors: Michael R. Turner; Sathy V. Balu-Iyer
      Abstract: Biotherapeutics are a rapidly growing drug class and well over 200 biotherapeutics have already obtained approval, with about fifty of these being approved in 2015 and 2016 alone 1. Several hundred protein therapeutic products are still in the pipeline, including interesting new approaches to treatment. Due to patients’ convenience of at home administration and reduced number of hospital visits as well as the reduction in treatment costs, subcutaneous (SC) administration of biologics is of increasing interest.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-11
      DOI: 10.1016/j.xphs.2018.01.007
  • Surfactant effects on lipid-based vesicles properties
    • Authors: Ruba Bnyan; Iftikhar Khan, Touraj Ehtezazi, Imran Saleem, Sarah Gordon, Francis O’ Neill, Matthew Roberts
      Abstract: Understanding the effect of surfactant properties is critical when designing vesicular delivery systems. This review evaluates previous studies to explain the influence of surfactant properties on the behaviour of lipid vesicular systems, specifically their size, charge, stability, entrapment efficiency (EE), pharmacokinetics, and pharmacodynamics. Generally, the size of vesicles decreases by increasing the surfactant concentration, carbon chain length, the hydrophilicity of the surfactant head group, and the hydrophilic-lipophilic balance (HLB).
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-11
      DOI: 10.1016/j.xphs.2018.01.005
  • Population pharmacokinetics of high-dose methotrexate in patients with
           primary central nervous system lymphoma
    • Authors: Shenghui Mei; Xingang Li, Xueyun Jiang, Kefu Yu, Song Lin, Zhigang Zhao
      Abstract: The intra- and inter-individual variances of methotrexate (MTX) pharmacokinetics are extremely large, and the pharmacokinetic property of MTX in patients with primary central nervous system lymphoma (PCNSL) is unestablished. A total of 701 MTX plasma concentrations from 98 patients with PCNSL under High-dose methotrexate (HDMTX) therapy were used to develop the population pharmacokinetic (popPK) model of MTX by using the nonlinear mixed-effects modeling method. A two-compartment model was employed to describe the pharmacokinetic property of MTX.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-10
      DOI: 10.1016/j.xphs.2018.01.004
  • Improved Human Pharmacokinetic Prediction of Hepatically Metabolized Drugs
           with Species-Specific Systemic Clearance
    • Authors: Kana Horiuchi; Shuichi Ohnishi, Takanobu Matsuzaki, Satoko Funaki, Ayahisa Watanabe, Tohru Mizutare, Sayaka Matsumoto, Kenichi Nezasa, Hiroshi Hasegawa
      Abstract: Accurate prediction of human pharmacokinetics (PK) is important for the choice of promising compounds in humans. As the predictability of human PK by an empirical approach is low for drugs with species-specific PK, the utility of a physiologically based pharmacokinetic (PBPK) model was verified using 16 reference drugs hepatically metabolized. After the prediction method for total clearance (CLtot) and distribution volume at steady state (Vdss) in the conventional PBPK model had been optimized, plasma concentrations following a single oral administration of each reference drug to healthy volunteers were simulated and the prediction accuracy for human PK was compared between empirical approaches and the optimized PBPK model.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-10
      DOI: 10.1016/j.xphs.2017.12.027
  • Prediction of the Hydrogen Peroxide Induced Methionine Oxidation
           Propensity in Monoclonal Antibodies
    • Authors: Neeraj J. Agrawal; Andrew Dykstra, Jane Yang, Hai Yue, Xichdao Nguyen, Carl Kolvenbach, Nicolas Angell
      Abstract: Methionine oxidation in therapeutic antibodies can impact the product’s stability, clinical efficacy and safety and hence it is desirable to address the methionine oxidation liability during antibody discovery and development phase. While the current experimental approaches can identify the oxidation labile methionine residues, their application is limited mostly to the development phase. We demonstrate an in silico method that can be used to predict oxidation labile residues based solely on the antibody sequence and structure information.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-08
      DOI: 10.1016/j.xphs.2018.01.002
  • Microfluidic approaches for the characterization of therapeutic proteins
    • Authors: Marie R.G. Kopp; Paolo Arosio
      Abstract: In the last decades the pharmaceutical market has experienced an increase in the number of therapeutic proteins. The high activity and selectivity of these macromolecules is often achieved at the expense of complex structures, which exhibit several biophysical properties that must be carefully controlled and optimized for the successful development of these drugs as well as for guaranteeing their quality and safety. This need has motivated the application of a variety of biophysical techniques to analyze properties of therapeutic proteins and protein solutions including interactions, aggregation, solubility, viscosity and thermal stability.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-08
      DOI: 10.1016/j.xphs.2018.01.001
  • Oral Delivery of Highly Lipophilic Poorly Water-Soluble Drugs:
           Self-Emulsifying Drug Delivery Systems (SEDDS) to Improve Oral Absorption
           and Enable High Dose Toxicology Studies of a CETP Inhibitor in Preclinical
    • Authors: Xue-Qing Chen; Theresa Ziemba, Christine Huang, Ming Chang, Carrie Xu, Jennifer X. Qiao, Tammy C. Wang, Heather J. Finlay, Mark E. Salvati, Leonard P. Adam, Olafur Gudmundsson, Michael J. Hageman
      Abstract: BMS-A is a highly lipophilic compound (clogP 10.5) with poor aqueous solubility (< 0.0001 mg/mL at pH 6.5). The compound exhibits low oral exposure when dosed as cosolvent solution formulations. The purpose of this study was to evaluate lipid-based formulations for enabling high-dose toxicology studies and enhancing toxicology margins of BMS-A in pre-GLP studies in non-rodent species. The solubility of BMS-A was screened in lipid and cosolvent/surfactant excipients and prototype formulations were developed.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-06
      DOI: 10.1016/j.xphs.2018.01.003
  • Ophthalmic econazole hydrogels for the treatment of fungal keratitis
    • Authors: Victoria Díaz-Tomé; Andrea Luaces-Rodríguez, Jesús Silva-Rodríguez, Sara Blanco-Dorado, Laura García-Quintanilla, José Llovo Taboada, José Blanco-Méndez, Michel Herranz, María Gil-Martínez, María Jesús Lamas, Miguel González-Barcia, Francisco J. Otero-Espinar, Anxo Fernández-Ferreiro
      Abstract: Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest a-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterised in solution by 1D, 2D-NMR and molecular modelling.
      Citation: Journal of Pharmaceutical Sciences (2018)
      PubDate: 2018-01-03
      DOI: 10.1016/j.xphs.2017.12.028
  • Design and evaluation of bi-layer pump tablet of flurbiprofen solid
           dispersion for zero-order controlled delivery
    • Authors: Lizhen Cheng; Ting Li, Ling Dong, Xiaoyu Wang, Qiye Huo, Haoyu Wang, Zhujun Jang, Xinyu Shan, Weisan Pan, Xinggang Yang
      Abstract: In this study, a bi-layer osmotic pump tablet (OPT) of Flurbiprofen (FP) solid dispersions (SDs) was developed to increase the solubility of the poorly soluble drug and control drug release at a constant rate. Based on the thermodynamic properties investigation of the drug, the carrier and the calculation of the solubility parameters, the FP-SD was prepared by hot melt extrusion (HME) technique with the carrier of PVPVA64. Then central composite design-response surface methodology (CCD-RSM) was used to evaluate the influence of factors on the responses.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-29
      DOI: 10.1016/j.xphs.2017.12.026
  • 5-FU-induced gastrointestinal damage impairs the absorption and
           anticoagulant effects of dabigatran etexilate
    • Authors: Kazunari Tsujii; Tomoki Hattori, Ayuko Imaoka, Takeshi Akiyoshi, Hisakazu Ohtani
      Abstract: Fluoropyrimidines, including 5-fluororacil (5-FU), cause gastrointestinal damage in the clinical setting and might affect the gastrointestinal absorption of concomitantly administered drugs. We aimed to evaluate the effects of fluoropyrimidine-induced gastrointestinal damage on the pharmacokinetics and pharmacodynamics of dabigatran etexilate (DABE), an anticoagulant, in rats with gastrointestinal damage induced by the repeated oral administration of 5-FU.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-29
      DOI: 10.1016/j.xphs.2017.12.023
  • Modeling of a hybrid Langmuir adsorption isotherm for describing
           interactions between drug molecules and silica surfaces
    • Authors: Thomas Sandberg; Christian Weinberger, Didem Şen Karaman, Jessica M. Rosenholm
      Abstract: The interaction between disulfiram (Antabus®) and silica was studied experimentally by adsorption from apolar solvent onto highly porous silica material (Santa Barbara Amorphous material-3, SBA-3) with large surface area. The adsorption isotherm was fitted to the Langmuir model by accounting two different affinities contributing to the overall behavior, which were attributed to two different types of silanol groups (i.e. geminal and vicinal) present on amorphous silica surfaces. This assumption was supported by theoretical calculations.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-28
      DOI: 10.1016/j.xphs.2017.12.025
  • Investigating the impact of drug crystallinity in amorphous tacrolimus
           capsules on pharmacokinetics and bioequivalence using discriminatory in
           vitro dissolution testing and PBPK modeling and simulation
    • Authors: Hitesh S. Purohit; Niraj S. Trasi, Dajun D. Sun, Edwin C.Y. Chow, Hong Wen, Xinyuan Zhang, Yi Gao, Lynne S. Taylor
      Abstract: Delivering a drug in amorphous form in a formulated product is a strategy used to enhance the apparent solubility of a drug substance and its oral bioavailability. Drug crystallization in such products may occur during the manufacturing process or upon storage, reducing the solubility advantage of the amorphous drug. However, the impact of partial drug crystallization in the drug product on the resulting bioavailability and pharmacokinetics is unknown. In this study, dissolution testing of commercial tacrolimus capsules (which are formulated to contain amorphous drug), both fresh and those containing different amounts of crystalline drug, was conducted using both USP and non-compendial dissolution tests with different dissolution media and volumes.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-28
      DOI: 10.1016/j.xphs.2017.12.024
  • Editorial
    • Authors: Ronald T. Borchardt
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-26
      DOI: 10.1016/j.xphs.2017.12.022
  • Making All Medications Gluten-free
    • Authors: Ankita V. Shah; Abu T.M. Serajuddin, Robert A. Mangione
      Abstract: Gluten is found in food containing wheat, rye and barley, and it may be introduced into medicines through the use of starch or any modified form of starch derived from these grains. The ingestion of gluten poses serious health hazards to people with celiac disease (CD) and non-celiac gluten sensitivity (NCGS), and they must avoid the oral ingestion of gluten. In 2011, the FDA solicited information and public comments on ‘gluten in drug products’. However, the ‘final rule’ that the Agency issued in 2013 involved only the voluntary ‘gluten-free’ labeling of food, and it did not include drug products.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-26
      DOI: 10.1016/j.xphs.2017.12.021
  • PTL401, a New Formulation Based on Pro-nano Dispersion Technology,
           Improves Oral Cannabinoids Bioavailability in Healthy Volunteers
    • Authors: Jacob Atsmon; Irina Cherniakov, Dvora Izgelov, Amnon Hoffman, Abraham J. Domb, Lisa Deutsch, Frederic Deutsch, Daphna Heffetz, Hagit Sacks
      Abstract: There is growing clinical interest in developing and commercializing pharmaceutical-grade cannabinoid products, containing primarily tetrahydrocannabinol (THC) and cannabidiol (CBD). The oral bioavailability of THC and CBD is very low due to extensive “first pass” metabolism. A novel oral THC and CBD formulation, PTL401, utilizing an advanced self-emulsifying oral drug delivery system, was designed to circumvent the “first pass” effect. In this study, the bioavailability of THC and CBD from the PTL401 capsule was compared with similar doses from a marketed reference oromucosal spray (Sativex®).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-26
      DOI: 10.1016/j.xphs.2017.12.020
  • World Health Organization and Essential Medicines
    • Authors: Sagar Dugani; Kishor M. Wasan, Niranjan Kissoon
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-22
      DOI: 10.1016/j.xphs.2017.12.019
  • Using Image Attributes to Assure Accurate Particle Size and Count Using
           Nanoparticle Tracking Analysis
    • Authors: Adrian P. Defante; Wyatt N. Vreeland, Kurt D. Benkstein, Dean C. Ripple
      Abstract: Nanoparticle tracking analysis (NTA) obtains particle size by analysis of particle diffusion through a time series of micrographs and particle count by a count of imaged particles. The number of observed particles imaged is controlled by the scattering cross-section of the particles and by camera settings such as sensitivity and shutter speed. Appropriate camera settings are defined as those that image, track, and analyze a sufficient number of particles for statistical repeatability. Here, we test if image attributes, features captured within the image itself, can provide measurable guidelines to assess the accuracy for particle size and count measurements using NTA.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-22
      DOI: 10.1016/j.xphs.2017.12.016
  • Population pharmacokinetics and dosing simulations of ceftazidime in
           Chinese neonates
    • Authors: Honghong Wang; Xingang Li, Shusen Sun, Guifu Mao, Ping Xiao, Chan Fu, Zhuoxin Liang, Min Zheng, Yuling Huang, Haihong Tang, Renhao Ou, Ni Yang, Xi Ling, Zhigang Zhao
      Abstract: An accurate dosage determination is required in neonates when antibiotics are used. The adult data cannot be simply extrapolated to the pediatric population due to significant individual differences. We aimed to identify factors impacting ceftazidime exposure in neonates and to provide drug dosing guidance to clinicians. 43 neonates aged less than 60 days with proven or suspected infections were enrolled in this study. After intravenous administration, blood samples were collected, and plasma ceftazidime concentration was determined using a high-performance liquid chromatography method.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-21
      DOI: 10.1016/j.xphs.2017.12.018
  • Proliferation, Metabolic Activity and Adipogenic Differentiation of Human
           Preadipocytes Exposed to Two Surfactants in vitro
    • Authors: Tim Ruhl; Gabriele Storti, Norbert Pallua
      Abstract: Fat grafting is a pivotal technique for tissue repair. Adipose stromal cells, including preadipocytes, play a major role in the regenerative effects attributed to fat grafting. But the benefits are impaired by the low survival of the graft due to mechanical stress during harvesting, hypoxia and nutrient deprivation. Non-ionic surfactant molecules demonstrated their efficacy in preventing and repairing mechanical damage on the cellular membrane, but it is poorly understood if and how they affect cellular viability, proliferation and differentiation.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-21
      DOI: 10.1016/j.xphs.2017.12.017
  • Predicting protein-protein interactions of concentrated antibody solutions
           using dilute solution data and coarse-grained molecular models
    • Authors: Cesar Calero-Rubio; Ranendu Ghosh, Atul Saluja, Christopher J. Roberts
      Abstract: Protein-protein interactions for solutions of an IgG1 molecule were quantified using static light scattering (SLS) measurements from low to high protein concentrations (c2). SLS was used to determine second osmotic virial coefficients (B22) at low c2, and excess Rayleigh profiles (Rex/K vs c2) and zero-q structure factors (Sq=0) as a function of c2 at higher c2 for a series of conditions (pH, sucrose concentration, and total ionic strength (TIS)). Repulsive (attractive) interactions were observed at low TIS (high TIS) for pH 5 and 6.5, with increasing repulsions when 5% w/w sucrose was also present.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-21
      DOI: 10.1016/j.xphs.2017.12.015
  • Characterization and stability of Trypanosoma cruzi 24-C4 (Tc24-C4), a
           candidate antigen for a therapeutic vaccine against Chagas disease
    • Authors: Amadeo B. Biter; Sarah Weltje, Elissa M. Hudspeth, Christopher A. Seid, C. Patrick McAtee, Wen-Hsiang Chen, Jeroen B. Pollet, Ulrich Strych, Peter J. Hotez, Maria Elena Bottazzi
      Abstract: Chagas disease due to chronic infection with Trypanosoma cruzi is a neglected cause of heart disease, affecting approximately 6-10 million individuals in Latin America and elsewhere. T. cruzi Tc24, a calcium-binding protein in the flagellar pocket of the parasite, is a candidate antigen for an injectable therapeutic vaccine as an alternative or a complement to chemotherapy. Previously, we reported that a genetically engineered construct from which all cysteine residues had been eliminated (Tc24-C4) yields a recombinant protein with reduced aggregation and improved analytical purity in comparison to the wild-type form, without compromising antigenicity and immunogenicity.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-21
      DOI: 10.1016/j.xphs.2017.12.014
  • Estimation of melting points of organics
    • Authors: Samuel H. Yalkowsky; Doaa Alantary
      Abstract: UPPER (Unified Physical Property Estimation Relationships) is a system of empirical and theoretical relationships that relate twenty physicochemical properties of organic molecules to each other and to chemical structure. Melting point is a key parameter in the UPPER Scheme because it is a determinant of several other properties including vapor pressure, and Solubility. This review describes the first principals calculation of the melting points of organic compounds from structure. The calculation is based on the fact that the melting point, Tm, is equal to the ratio of the heat of melting, ΔHm, to the entropy of melting, ΔSm.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-21
      DOI: 10.1016/j.xphs.2017.12.013
  • Bile acid as an effective absorption enhancer for oral delivery of
           EGFR-targeted hybrid peptide
    • Authors: Arong Gaowa; Tomohisa Horibe, Masayuki Kohno, Koji Kawakami
      Abstract: The aim of this study was to improve the oral absorption of epidermal growth factor receptor (EGFR)-targeted hybrid peptide using bile acid as an absorption enhancer. The oral formulation of this peptide was formed through electrostatic interactions between the cationic peptide and anionic bile acid. Comparative studies of in vitro cell permeability and in vivo anti-tumor effects of peptide and peptide/bile acid complex were performed in Caco-2 cells and in a xenograft mouse model of human gastric cancer.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-19
      DOI: 10.1016/j.xphs.2017.12.012
  • Characterization of Water Self-Diffusion in Human Stratum Corneum
    • Authors: Chandana Kodiweera; Yuan Yang, Annette L. Bunge
      Abstract: The stratum corneum (SC) is the outermost layer of human skin and primary barrier to water loss and chemical exposure. It consists of keratin-filled corneocytes of large aspect ratio surrounded by a thin matrix of highly organized lipophilic molecules. In the presence of water, the corneocytes swell and permeability for many chemicals increases. The role of hydration and SC structure on water self-diffusion was investigated using the pulsed-gradient stimulated echo (PGSTE) nuclear magnetic resonance (NMR) technique.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-19
      DOI: 10.1016/j.xphs.2017.12.011
  • A measurement and modelling study of hair partition of neutral, cationic
           and anionic chemicals
    • Authors: Lingyi Li; Senpei Yang, Tao Chen, Lujia Han, Guoping Lian
      Abstract: Various neutral, cationic and anionic chemicals contained in hair care products can be absorbed into hair fiber to modulate physicochemical properties such as color, strength, style and volume. For environmental safety, there is also an interest in understanding hair absorption to wide chemical pollutants. There have been very limited studies on the absorption properties of chemicals into hair. Here, an experimental and modelling study has been carried out for the hair-water partition of a range of neutral, cationic and anionic chemicals at different pH.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-18
      DOI: 10.1016/j.xphs.2017.12.010
  • Evaluation of Hydrogen Exchange Mass Spectrometry as a
           Stability-Indicating Method for Formulation Excipient Screening for an
           IgG4 Monoclonal Antibody
    • Authors: Ronald T. Toth; Samantha E. Pace, Brittney J. Mills, Sangeeta B. Joshi, Reza Esfandiary, C. Russell Middaugh, David D. Weis, David B. Volkin
      Abstract: Antibodies are molecules that exhibit diverse conformational changes on different timescales and there is ongoing interest to better understand the relationship between antibody conformational dynamics and storage stability. Physical stability data for an IgG4 monoclonal antibody (mAb-D) were gathered through traditional forced degradation (temperature and stirring stresses) and accelerated stability studies, in the presence of different additives and solution conditions, as measured by differential scanning calorimetry, size exclusion chromatography and microflow imaging.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-18
      DOI: 10.1016/j.xphs.2017.12.009
  • Deep Convolutional Neural Network Analysis of Flow Imaging Microscopy Data
           to Classify Subvisible Particles in Protein Formulations
    • Authors: Christopher P. Calderon; Austin L. Daniels, Theodore W. Randolph
      Abstract: Flow-Imaging Microscopy (FIM) is commonly used to characterize subvisible particles in therapeutic protein formulations. Although pharmaceutical companies often collect large repositories of FIM images of protein therapeutic products, current state-of-the-art methods for analyzing these images rely on low-dimensional lists of “morphological features” to characterize particles that ignore much of the information encoded in the existing image databases. Deep Convolutional Neural Networks (“ConvNets”) have demonstrated the ability to extract predictive information from raw macroscopic image data without requiring the selection or specification of “morphological features'' in a variety of tasks.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-18
      DOI: 10.1016/j.xphs.2017.12.008
  • Metabolic pathway of icotinib in vitro: the differential roles of CYP3A4,
           CYP3A5 and CYP1A2 on potential pharmacokinetic drug-drug interaction
    • Authors: TianHong Zhang; KeRong Zhang, Li Ma, Zheng Li, Juan Wang, YunXia Zhang, Chuang Lu, MingShe Zhu, XiaoMei Zhuang
      Abstract: Icotinib is the self-developed small molecule drug in China for targeted therapy of non-small-cell lung cancer. To date, systematic studies on the pharmacokinetic drug-drug interaction (DDI) of icotinib were limited. By identifying metabolite generation in human liver microsomes (HLM) and revealing the contributions of major CYPs in the formation of major metabolites, the aim of the present work is to understand the mechanisms underlying pharmacokinetic and pharmacological variability in clinic.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-13
      DOI: 10.1016/j.xphs.2017.12.007
  • Investigations on the Mechanism of Magnesium Stearate to Modify Aerosol
           Performance in Dry Powder Inhaled Formulations
    • Authors: Martin Jetzer; Marcel Schneider, Bradley Morrical, Georgios Imanidis
      Abstract: The potential of the force control agent (FCA) magnesium stearate (MgSt) to enhance the aerosol performance of lactose-based dry powder inhaled (DPI) formulations was investigated in this study. The excipient blends were investigated with analytical techniques including time-of-flight secondary ion mass spectrometry (ToF-SIMS) and Single Particle Aerosol Mass Spectrometry (SPAMS) and particle size, morphology and surface properties were evaluated. Excipient-blends were manufactured either by high-shear or low-shear blending lactose carrier with different amounts of MgSt in the range from 0-10% (w/w).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-13
      DOI: 10.1016/j.xphs.2017.12.006
  • Role of Solvent Selection on Crystal Habit of 5-Aminosalicylic Acid –
           Combined Experimental and Computational Approach
    • Authors: Nawin Pudasaini; Christian R. Parker, Stefan U. Hagen, Andrew D. Bond, Jukka Rantanen
      Abstract: Many active pharmaceutical ingredients (API) exhibit a needle-like (acicular) crystal habit, which can significantly complicate their downstream processing. In this study, the acicular crystal habit of a model API, 5-aminosalicylic acid (5-ASA), was modified by addition of selected organic solvents to the typical aqueous crystallization process. 5-ASA was crystallized by a pH shift from 7.5-8 to 4 in the presence of methanol, acetonitrile, acetone, tetramethylurea (TMU), tetrahydrofuran (THF) or dimethyl sulfoxide (DMSO) at 25% v/v, or butanol at 9% v/v.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-13
      DOI: 10.1016/j.xphs.2017.12.005
  • Cellular Pharmacokinetic Model-based Analysis of Genistein, Glyceollin and
           MK-571 Effects on 5 (and 6)-Carboxy-2’,7’-Dichloroflourescein
           Disposition in Caco-2 Cells
    • Authors: Callie Drennen; Erin Gorse, Robert E. Stratford
      Abstract: Pharmacokinetic modeling was used to describe 5 (and 6)-Carboxy-2’,7’-Dichloroflourescein (CDF) disposition in Caco-2 cells following CDF or CDFDA (CDF diacetate) dosing. CDF transcellular flux was modeled by simple passive diffusion. CDFDA-dosing models were based on simultaneous fitting of CDF levels in apical, basolateral and intracellular compartments. Predicted CDF efflux was 50% higher across the apical versus the basolateral membrane. This difference was similar following apical and basolateral CDFDA dosing, despite intracellular levels being three-fold higher following basolateral dosing, thus supporting non-saturable CDF efflux kinetics.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-13
      DOI: 10.1016/j.xphs.2017.12.004
  • Roll compaction/dry granulation of dibasic calcium phosphate anhydrous -
           Does the morphology of the raw material influence the tabletability of dry
    • Authors: Simon Grote; Peter Kleinebudde
      Abstract: The influence of raw material particle morphology on the tabletabilty of dry granules was investigated. Therefore, dibasic calcium phosphate anhydrous was used as a model material. One milled grade, two agglomerated grades with different porosities and a functionalized structure, i.e. an agglomerate formed by very small primary particles, were included. Particle size, density and specific surface area of raw materials were measured. The starting materials and two fractions of dry granules were compressed to tablets.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-13
      DOI: 10.1016/j.xphs.2017.12.003
  • Fatty acid binding protein 5 mediates the uptake of fatty acids, but not
           drugs, into human brain endothelial cells
    • Authors: Gordon S. Lee; Yijun Pan, Martin J. Scanlon, Christopher J.H. Porter, Joseph A. Nicolazzo
      Abstract: The purpose of this study was to examine the involvement of fatty acid binding protein 5 (FABP5), a lipid binding protein expressed at the blood-brain barrier (BBB), in fatty acid and drug uptake into human brain endothelial cells. Following transfection with siRNA against hFABP5, human brain endothelial cell (hCMEC/D3) uptake of lipophilic ligands with varying affinity to FABP5 was assessed with intracellular concentrations quantified by liquid scintillation counting, HPLC or LCMS/MS. The in situ BBB transport of [3H]-diazepam was also assessed in wild type (WT) and FABP5-deficient mice.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-13
      DOI: 10.1016/j.xphs.2017.11.024
  • Crystal and particle engineering strategies for improving powder
           compression and flow properties to enable continuous tablet manufacturing
           by direct compression
    • Authors: Sayantan Chattoraj; Changquan Calvin Sun
      Abstract: Continuous manufacturing of tablets has many advantages, including batch size flexibility, demand-adaptive scale up or scale down, consistent product quality, small operational foot print, and increased manufacturing efficiency. Simplicity makes direct compression the most suitable process for continuous tablet manufacturing. However, deficiencies in powder flow and compression of active pharmaceutical ingredients (API) limit the range of drug loading that can routinely be considered for direct compression.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-13
      DOI: 10.1016/j.xphs.2017.11.023
  • Understanding the Factors that Control the Quality of Mini-tablet
           Compression: Flow, Particle Size and Tooling Dimension
    • Authors: Junshu Zhao; David Yin, Jasmine Rowe, Sherif Badawy, Faranak Nikfar, Preetanshu Pandey
      Abstract: Despite the increasing importance of mini-tablet for its advantages as pediatric formulations and in modified release applications, its popularity is limited due to the lack of formulation and processing knowledge in developing such dosage forms. In this study, common grades of microcrystalline cellulose and roller compacted granules with a range of powder properties were used to evaluate the critical material properties required for the successful manufacturing of 1.7 mm mini-tablets. It was found that blends with small particle size had poor flow properties that did not support consistent die filling and also tended to cause tooling jam and damage.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-09
      DOI: 10.1016/j.xphs.2017.12.002
  • Characterization of the hydrodynamics in a miniaturized dissolution
    • Authors: Kristoffer E. Johansson; Jakob Plum, Majid Mosleh, Cecilie M. Madsen, Thomas Rades, Anette Müllertz
      Abstract: The hydrodynamics of a miniaturized dissolution apparatus was characterized using computational fluid dynamics (CFD) simulations and analyzed in relation to the biorelevance and robustness of measurements of drug dissolution and precipitation kinetics from supersaturated drug solutions. The effect of using three different agitator geometries operated at 50, 100, 150 and 200 RPM as well as different positioning of an UV probe in the vessel was systematically evaluated. The CFD simulations were validated using a particle streak velocimetry experiment.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-09
      DOI: 10.1016/j.xphs.2017.11.022
  • A mathematic model and experimental verification of optimal nozzle
           diameter in needle-free injection
    • Authors: Dongping Zeng; Yong Kang, Lu Xie, Xiaoxiao Xia, Zefeng Wang, Wenchuan Liu
      Abstract: Needle-free injection, as an alternative drug delivery strategy, owns great potential. It is able to reduce complaints about needle phobia and avoid the occurring of accidental needle stick injuries. The nozzle diameter is inherently important in determining the injection dose, injection depth and pain associated with needle-free injections. In this work, needle-free injectors with nozzle diameters of 0.17 mm, 0.20 mm, 0.30 mm, 0.40mm, 0.50 mm were studied in the simulation and experiment. This paper optimizes the mathematical model for spring powered needle-free injection by considering the hydraulic loss due to the abrupt change in the nozzle exit area and the friction force between the piston and ampoule.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-09
      DOI: 10.1016/j.xphs.2017.12.001
  • Active Mediated Transport of Chloramphenicol and Thiamphenicol in a Calu-3
           Lung Epithelial Cell Model
    • Authors: S.N. Nurbaeti; J.C. Olivier, C. Adier, S. Marchand, W. Couet, J. Brillault
      Abstract: Pulmonary administration enables high local concentrations along with limited systemic side-effects, but not all ATB could be good candidates. In this perspective, diffusion of the ATB chloramphenicol (CHL) and thiamphenicol (THA) through the lung has been evaluated to re-assess their potential for pulmonary administration. The apparent permeability (Papp) was evaluated with the Calu-3 cell model. Influence of drug transporters was assessed with the PSC-833, MK-571, and KO-143 inhibitors. The influence of CHL and THA on the cell uptake of rhodamin123 and fluorescein was also evaluated.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-05
      DOI: 10.1016/j.xphs.2017.11.021
  • On the production of chitosan coated PCL nanoparticles in a Confined
           Impinging Jets Reactor
    • Authors: Tereza Zelenková; Maria Julia Mora, Antonello A. Barresi, Gladys Ester Granero, Davide Fissore
      Abstract: This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in a confined impinging jets reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, e.g. polycaprolactone, is required to support chitosan to obtain a mono-modal particle size distribution, with low particle diameters. A surfactant is required to reduce nanoparticles size (down to a mean diameter of about 260 nm) and obtain a positive Zeta potential (about +31 mV), perfectly suitable for pharmaceutical applications.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-05
      DOI: 10.1016/j.xphs.2017.11.020
  • The Application of 3D Printing in the Formulation of Multilayered Fast
           Dissolving Oral Films
    • Authors: Touraj Ehtezazi; Marwan Algellay, Yamir Islam, Matt Roberts, Nicola M. Dempster, Satyajit D. Sarker
      Abstract: Fast dissolving oral films (FDFs) provide an alternative approach to increase consumer acceptance by advantage of rapid dissolution and administration without water. Usually FDFs require taste-masking agents. However, inclusion of these excipients could make developing the formulation a challenging task. Hence, this work employed fused-deposition modelling three-dimensional (FDM 3D) printing to produce single-layered (SLFDFs), or multilayered (MLFDFs) films, with taste-masking layers being separated from drug layer.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-12-02
      DOI: 10.1016/j.xphs.2017.11.019
  • Thermodynamic Estimate of the Number of Solvent Molecules Displaced by a
           Solute Molecule for Enthalpy-Driven Adsorption: Phenobarbital and
           Activated Carbons as the Model System
    • Authors: Peng Yu; Dale Eric Wurster
      Abstract: A Modified Crisp Equation, describing the differential Gibbs free energy of the adsorption process, is being proposed, which considers multiple sites available on the surface for adsorption and their relative fractions. The differential Gibbs free energy can be calculated by the van’t Hoff Equation, which depends on the affinity constant in the Langmuir-Like Equation. To consider the number of solvent molecules displaced by a solute molecule in the adsorption process, a new derivative of the Langmuir-Like Equation is being proposed as well.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-27
      DOI: 10.1016/j.xphs.2017.11.017
  • Development and Characterization of Chitosan Crosslinked with
           Tripolyphosphate as a Sustained Release Agent in Tablets. Part I. Design
           of Experiments and Optimization
    • Authors: Colin A. Pinto; Kalyan K. Saripella, Nikhil C. Loka, Steven H. Neau
      Abstract: Certain issues with the use of particles of chitosan (Ch) crosslinked with tripolyphosphate (TPP) in sustained release formulations include inefficient drug loading, burst drug release, and incomplete drug release. Acetaminophen was added to Ch:TPP particles to test for advantages to drug addition extragranularly over during crosslinking. The influences of chitosan concentration, Ch:TPP ratio, temperature, ionic strength, and pH were assessed. Design of experiments allowed identification of factors and two factor interactions that have significant effects on average particle size and size distribution, yield, zeta potential, and true density of the particles, as well as drug release from the directly compressed tablets.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-25
      DOI: 10.1016/j.xphs.2017.11.018
  • Alginate-based hydrogel containing minoxidil/hydroxypropyl-β-cyclodextrin
           inclusion complex for topical alopecia treatment
    • Authors: Angela Lopedota; Nunzio Denora, Valentino Laquintana, Annalisa Cutrignelli, Antonio Lopalco, Domenico Tricarico, Fatima Maqoud, Angela Curci, Maria Mastrodonato, Flavia la Forgia, Sergio Fontana, Massimo Franco
      Abstract: Cutaneous minoxidil (MXD) formulations were developed with the intent to reduce the side effects of the cosolvents propylene glycol and ethanol, frequently used in commercial MXD solutions. Completely aqueous alginate-based hydrogels were investigated and MXD aqueous solubility was improved using inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD) at two different molar substitution degree (MS), namely 0.65 and 0.85. HP-β-CD MS 0.65 was selected for its improved solubilizing ability toward MXD.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-25
      DOI: 10.1016/j.xphs.2017.11.016
  • Arginine as an Excipient for Protein Freeze-Drying: A Mini-Review
    • Authors: Peter Stärtzel
      Abstract: Successful development of marketable freeze-dried protein formulations requires adequate stabilization of the active biopharmaceutical ingredient. The choice of a stabilizer must therefore be based on sound knowledge of the physical and chemical properties of the excipients and specific needs of the protein component. Amino acids, such as arginine, have exhibit cryo- and lyoprotective effects similar to those of sugars and/or polymers and may therefore be considered to be an alternative approach to these established formulation strategies.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-25
      DOI: 10.1016/j.xphs.2017.11.015
  • Curcumin co-crystal micelles - multifunctional nanocomposites for
           management of neurodegenerative ailments
    • Authors: Preshita P. Desai; Vandana B. Patravale
      Abstract: Curcumin, a potent antioxidant polyphenol with neuroprotective and antiamyloid activity has significant potential in the treatment of neurodegenerative disorders like Alzheimer’s disease. However, its clinical translation is delayed due to poor bioavailability. For effective use of curcumin in Alzheimer’s disease, it is imperative to increase its bioavailability with enhanced delivery at therapeutic site i.e. brain. With this objective, pharmaceutical co-crystals of curcumin were developed and incorporated in micellar nanocarriers for nose to brain delivery.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-25
      DOI: 10.1016/j.xphs.2017.11.014
  • Dissolving Microneedles Loaded with Etonogestrel Microcrystal Particles
           for Intradermal Sustained Delivery
    • Authors: Meilin He; Guozhong Yang, Suohui Zhang, Xiaoyu Zhao, Yunhua Gao
      Abstract: This study presents a design that lipophilic drug was encapsulated within dissolving microneedles (DMNs) for sustained-release delivery over one week. Etonogestrel (ENG), the progestogen used in hormonal contraceptives, was loaded in two-layered DMNs in form of microcrystal particles (MP). In vitro release study indicated that ENG in form of MP could sustain drug release compared to non-crystal form. Hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) was used to prepare the fast dissolving needle-tips and flexible back layer, respectively.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-23
      DOI: 10.1016/j.xphs.2017.11.013
  • Mechanistic PBPK model of the heart accounting for inter-individual
           variability - development and performance verification
    • Authors: Zofia Tylutki; Aleksander Mendyk, Sebastian Polak
      Abstract: Modern model-based approaches to cardiac safety and efficacy assessment require accurate drug concentration-effect relationship establishment. Thus, knowledge of the active concentration of drugs in heart tissue is desirable along with inter-subject variability influence estimation. To that end, we developed a mechanistic physiologically based pharmacokinetic (PBPK) model of the heart. The models were described with literature-derived parameters and written in R v.3.4.0. Five parameters were estimated.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-23
      DOI: 10.1016/j.xphs.2017.11.012
  • In Vitro, Ex Vivo and In Vivo Evaluation of a Dual pH/Redox Responsive
           Nanoliposomal Sludge for Transdermal Drug Delivery
    • Authors: Simphiwe Mavuso; Thashree Marimuthu, Pradeep Kumar, Pierre P.D. Kondiah, Lisa C. du Toit, Yahya E. Choonara, Viness Pillay
      Abstract: A dual pH/redox responsive copper-glyglycine-prednisolone succinate [Cu(glygly)(PS)]-loaded nanoliposomal (NL) sludge was successfully synthesized and optimized using a Box-Behnken design of experiments. Pre-formulation design variables indicated that relative ratios of phospholipids, considerably influences NL size, thus altering the degree of drug loading in the formulation. In vitro evaluation further confirmed optimum release kinetics of the NL sludge, corresponding closely to ex vivo permeation studies, demonstrating effective transdermal delivery of prednisone (PS) through a pig skin model, which closely resembles human skin anatomy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-23
      DOI: 10.1016/j.xphs.2017.11.011
  • Status Epilepticus Decreases Brain Cytochrome P450 2D4 Expression in Rats
    • Authors: Yuki Asai; Hatsuna Tanaka, Masayuki Nadai, Miki Katoh
      Abstract: Status epilepticus (SE) is a life-threatening neurological emergency characterized by frequent seizures. The present study aims at elucidating the effect of SE on CYP2D4 expression in the rat brain. To create a rat model of SE, Sprague-Dawley rats were intraperitoneally administered 10 mg/kg kainic acid. The CYP2D4 mRNA levels in the cortex and hippocampus of the SE rats were decreased by 0.38- and 0.39-fold, respectively. The protein level of octamer transcription factor 1 (Oct-1), which is involved in the transcriptional activation of CYP2D4 by binding to the CYP2D4 regulatory element, were also attenuated by 0.64- and 0.51-fold in these regions of the SE rat, suggesting that a reduction in Oct-1 may be involved in the CYP2D4 suppression.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-23
      DOI: 10.1016/j.xphs.2017.11.010
  • The effect of drug content reduction on the in vitro and in vivo
           properties of levonorgestrel releasing intravaginal rings
    • Authors: Rüdiger Nave; Tero Jalkanen, Christine Talling, Masato Kaneko, Shunji Matsuki, Joachim Höchel
      Abstract: Intravaginal rings (IVR) are an option for continuous administration of drugs in women. However, a considerable amount of excess drug often remains in the ring upon removal. The current study focuses on comparing two IVRs releasing levonorgestrel (LNG). Both formulations were designed to release 40 μg of LNG daily, however with a significant difference in the total amount of drug (10.6 mg vs 176.9 mg). Numerical simulations and in vitro release rate testing were utilized in designing the IVRs and confirming the similarity of drug release.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-23
      DOI: 10.1016/j.xphs.2017.11.009
  • 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
  • Journal of Pharmaceutical Sciences (2017)
    • Authors: Ronald T. Borchardt
      First page: 771
      PubDate: 2017-11-10
      DOI: 10.1016/j.xphs.2017.11.004
  • Predictive Screening Tools Used in High Concentration Protein Formulation
    • Authors: Melanie Hofmann; Henning Gieseler
      First page: 772
      Abstract: This review examines the use of predictive screening approaches in high concentration protein formulation development. In addition to the normal challenges associated with protein formulation development, for high concentration formulations, solubility, viscosity, and physical protein degradation play major roles. To overcome these challenges, multiple formulation conditions need to be evaluated such that it is desirable to have predictive but also low-volume and high throughput methods in order to identify optimal formulation conditions very early in development without time and material consuming setups.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-01
  • Pharmacological efficacy/toxicity of drugs: A Comprehensive update about
           the dynamic interplay of microbes
    • Authors: J.A. Gimenez-Bastida; L. Martinez, A. Moya-Pérez, J.M. Laparra
      First page: 778
      Abstract: Oral ingestion is a common, easy to access, route for therapeutic drugs to be delivered. The conception of the gastrointestinal tract as a passive physiological compartment has evolved towards a dynamic perspective of the same. Thus, microbiota plays an important role in contributing with additional metabolic capacities to its host as well as to its phenotypic heterogeneity. These adaptations in turn influence the efficacy and toxicity of a broad range of drugs. Notwithstanding, xenobiotics and therapeutic drugs affecting the microbiome’s activity also significantly impact metabolism affecting different organs and tissues, and thereby drugs’ toxicity/efficacy effects.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-26
  • Current Japanese Regulatory Systems for Generics and Biosimilars
    • Authors: Ryosuke Kuribayashi; Kenji Sawanobori
      First page: 785
      Abstract: Currently, biosimilar products are being actively developed around the world. One reason for this is the expiry of patents of original biopharmaceutical products with an extremely large market share because the biosimilar companies need to avoid infringing patents. A representative example of this is biosimilar versions of monoclonal antibodies. In Japan, the Ministry of Health, Labour and Welfare is promoting the use of biosimilar products because the market share of such products is currently extremely low compared with that of generic products.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-04
  • Impacting Global Health through Equipment Repurposing: Measurable Progress
           through the Accumulation of Many Tiny Victories
    • Authors: Nicole L. Buist; Ellen C. Minnihan, Katherine Young, Lihu Yang
      First page: 788
      Abstract: There is an active and growing effort occurring in laboratories throughout Africa to research the underpinnings of endemic communicable diseases, many of which are considered “neglected tropical diseases” as defined by the World Health Organization (WHO).1 Across the continent, scientists, doctors, health-care workers, and students investigate the in vitro activity of pharmacologically active extracts against known pathogens in hope of discovering new treatments for the diseases that affect the local population.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-23
  • Density and Shape Factor Terms in Stokes’ Equation for Aerodynamic
           Behavior of Aerosols
    • Authors: Anthony J. Hickey; David A. Edwards
      First page: 794
      Abstract: Pharmaceutical aerosols are used to treat many pulmonary diseases. The use of low density powders has proven useful to support efficient drug delivery. Measurements must account for the low density, spherical particle features contributing to aerodynamic behavior. Ideally, the aerodynamic particle size distribution (APSD) is measured experimentally. Without formal measurement of APSD, calculations may be performed using surrogate measures such as bulk or tapped density and dynamic shape factor in Stokes’ equation.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-14
      DOI: 10.1016/j.xphs.2017.11.005
  • Evaluation of a Biologic Formulation using Customized Design of Experiment
           and Novel Multidimensional Robustness Diagrams
    • Authors: Radhakrishna K. Maroju; Steve Barash, Charlene Brisbane
      First page: 797
      Abstract: Formulation development includes selection of appropriate excipients to stabilize the active pharmaceutical ingredient (API) throughout its recommended shelf-life, against potential excursions in its life cycle and sometimes to aid in delivery of the therapeutic into the patient. Identity and quantity of every ingredient in a therapeutic formulation are critical to achieve their intended purpose. Deviations from a target composition can result in manufacturing, safety and efficacy challenges. It is mandatory to establish robustness of a formulation for the expected changes in its composition arising from the qualified ‘process variability’ of the impacting process steps during manufacture.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-26
  • Rapid, Room Temperature Nanoparticle Drying and Low Energy Reconstitution
           via Electrospinning
    • Authors: Shani L. Levit; Ratib M. Stwodah, Christina Tang
      First page: 807
      Abstract: Nanoparticle formulations offer advantages over free drug; however, stability of the nanoparticle dispersions is a significant obstacle and drying is often required for long-term size stability. The main limitation of current drying methods is particle aggregation upon reconstitution which can be overcome with sonication (impractical in a clinical setting) or large amounts of cryoprotectants (result in hypertonic dispersions). Therefore, new approaches to nanoparticle drying are necessary. We demonstrate conversion of nanoparticle dispersions to a dry, thermostable form via electrospinning.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-26
  • Effect of Phosphate Ion on the Structure of Lumazine Synthase, an Antigen
           Presentation System from Bacillus anthracis
    • Authors: Yangjie Wei; Newton Wahome, Prashant Kumar, Neal Whitaker, Wendy L. Picking, C. Russell Middaugh
      First page: 814
      Abstract: Lumazine synthase (LS) is an oligomeric enzyme involved in the biosynthesis of riboflavin in microorganisms, fungi and plants. LS has become of significant interest to biomedical science because of its critical biological role and attractive structural properties for antigen presentation in vaccines. LS derived from Bacillus anthracis (BaLS) consists of 60 identical subunits forming an icosahedron. Its crystal structure has been solved, but its dynamic conformational properties have not yet been studied.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-15
  • Effect of Controlled Ice Nucleation on Stability of Lactate Dehydrogenase
           during Freeze-Drying
    • Authors: Rui Fang; Kazunari Tanaka, Vamsi Mudhivarthi, Robin H. Bogner, Michael J. Pikal
      First page: 824
      Abstract: Several controlled ice nucleation techniques have been developed to increase the efficiency of the freeze-drying process as well as to improve the quality of pharmaceutical products. Due to the reduction in ice surface area, these techniques have the potential to reduce the degradation of proteins labile during freezing. The objective of this study was to evaluate the effect of ice nucleation temperature on the in-process stability of lactate dehydrogenase (LDH). LDH in potassium phosphate buffer was nucleated at -4°C, -8°C, and -12°C using ControLyo™ or allowed to nucleate spontaneously.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-23
  • Lipidic Nanoparticles Comprising of Phosphatidylinositol Mitigate
           Immunogenicity and Improve Efficacy of Recombinant Human Acid
           Alpha-Glucosidase in a Murine Model of Pompe Disease
    • Authors: Jennifer L. Schneider; Robert K. Dingman, Sathy V. Balu-Iyer
      First page: 831
      Abstract: Enzyme replacement therapy with recombinant human acid α-glucosidase (rhGAA) is complicated by the formation of anti-rhGAA antibodies, a short circulating half-life, instability in the plasma, and limited uptake into target tissue. Previously, we have demonstrated that phosphatidylinositol (PI) containing liposomes can reduce the immunogenicity and extend plasma survival of Factor VIII (FVIII) in a mouse model of Hemophilia A. In this manuscript we investigate the ability of PI liposomes to be used as a delivery vehicle to overcome the issues that complicate therapy with rhGAA.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-01
  • Manipulating aggregation behaviour of the uncharged peptide carbetocin
    • Authors: Ulrich B. Høgstedt; Jesper Østergaard, Torsten Weiss, Helen Sjögren, Marco van de Weert
      First page: 838
      Abstract: Peptides are usually administered through subcutaneous injection. For low potency drugs, this may require high concentration formulations increasing the risk of peptide aggregation, especially for compounds without any intrinsic chargeable groups. Carbetocin was used as a model to study the behaviour of uncharged peptides at high concentrations. Manipulation of the aggregation behaviour of 70 mg/ml carbetocin was attempted by selecting excipients which interact with hydrophobic groups in carbetocin, and/or cover hydrophobic surfaces and interfaces.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-20
      DOI: 10.1016/j.xphs.2017.11.008
  • Dual Therapeutic Effects of an Albumin-based Nitric Oxide Donor on Two
           Experimental Models of Chronic Kidney Disease
    • Authors: Shun Oshiro; Yu Ishima, Maeda Hitoshi, Naoko Honda, Bi Jing, Ryo Kinoshita, Mayumi Ikeda, Yasunori Iwao, Tadashi Imafuku, Kento Nishida, Sigeyuki Miyamura, Hiroshi Watanabe, Masaki Otagiri, Toru Maruyama
      First page: 848
      Abstract: Chronic kidney disease (CKD) is accompanied by a variety of complications, typically renal anemia and kidney fibrosis. Accordingly, it is desirable to develop the novel therapeutics that can treat these CKD conditions. Since nitric oxide (NO) has multiple functions including hypoxia inducible factor (HIF) stabilizing, anti-inflammatory, anti-oxidative and anti-apoptoic activities, the use of NO for the CKD therapy has attracted considerable interest. Here, we evaluate the therapeutic impacts of S-nitrosated human serum albumin (SNO-HSA), a long-lasting NO donor, on two animal models of CKD.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-23
  • Proof of Principle for Local Delivery of a c-Met Inhibitor
    • Authors: Howard Li; Irina Kadiyala, Michael Briggs, Rebecca Shawgo, Karem Reda, Rima Patel, Kirk Tanner, Francoise Berlioz-Seux, Brinley Furey, Patricia Hurter, Diane M. Boucher
      First page: 856
      Abstract: The reported proof of principle study demonstrated the feasibility of local delivery of a c-Met inhibitor (VXc-140) in a subcutaneous xenograft tumor model. VXc-140 was formulated in a wafer delivery system for direct implantation into the tumor. Systemic and local tumor exposure of VXc-140 was analyzed. High tumor exposures coupled with fast release of compound were associated with significant tumor regression and reduction in tumor levels of phosphorylated c-Met. High VXc-140 tumor-to-plasma ratios (∼42 at the tumor periphery) were achieved.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-26
  • Sustained Simultaneous Delivery of Metronidazole and Doxycycline From
           Polycaprolactone Matrices Designed for Intravaginal Treatment of Pelvic
           Inflammatory Disease
    • Authors: Meenakshi Pathak; Allan G.A. Coombes, BoMi Ryu, Peter J. Cabot, Mark S. Turner, Cheryn Palmer, Dongjie Wang, Kathryn J. Steadman
      First page: 863
      Abstract: Poly(ɛ-caprolactone) (PCL) intra-vaginal matrices were produced for local delivery of a combination of antibacterials, by rapidly cooling a mixture of drug powders dispersed in PCL solution. Matrices loaded with different combinations of metronidazole (10, 15 and 20% w/w) and doxycycline (10% w/w), were evaluated in vitro for release behavior and antibacterial activity. Rapid ‘burst release’ of 8-15% of the doxycycline content and 31-37% of the metronidazole content occurred within 24 h when matrices were immersed in simulated vaginal fluid (SVF) at 37°C.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-31
      DOI: 10.1016/j.xphs.2017.09.033
  • “Liquid crystalline systems based on glyceryl monooleate and penetration
           enhancers for skin delivery of celecoxib: characterization, in vitro drug
           release, and in vivo studies”
    • Authors: Mariane de Cássia Lima Dante; Livia Neves Borgheti-Cardoso, Marcia Carvalho de Abreu Fantini, Fabíola Silva Garcia Praça, Wanessa Silva Garcia Medina, Maria Bernadete Riemma Pierre, Marilisa Guimarães Lara
      First page: 870
      Abstract: Celecoxib (CXB) is a widely used anti-inflammatory drug that also acts as a chemopreventive agent against several types of cancer, including skin cancer. As the long-term oral administration of CXB has been associated with severe side effects, the skin delivery of this drug represents a promising alternative for the treatment of skin inflammatory conditions and/or chemoprevention of skin cancer. We prepared and characterized liquid crystalline systems based on glyceryl monooleate (GMO) and water containing penetration enhancers which were primarily designed to promote skin delivery of CXB.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-03
  • Can the cellular internalization of cargo proteins be enhanced by fusing a
           Tat peptide in the center of proteins' A fluorescence study
    • Authors: Xiaochao Chen; Jing Chen, Rong Fu, Pingfan Rao, Richard Weller, Jeremy Brasdshaw, Shutao Liu
      First page: 879
      Abstract: Aim to investigate whether the cellular uptake of cargo proteins can be enhanced by fusing a Tat peptide in the center of proteins, GST-Tat-GFP and GST-GFP-Tat proteins were firstly constructed and expressed. The cellular internalization of both proteins was then evaluated and compared in HeLa cells by using fluorescent microscopy and flow cytometry, as well as the transdermal delivery in human skin by using confocal microscopy. Results from in-vitro cell experiments showed that GST-Tat-GFP protein efficiently internalized into HeLa cells when a Tat peptide was fused in the center of proteins, whereas its efficiency is lower than that of GST-GFP-Tat protein with a Tat peptide terminal fused.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-10
      DOI: 10.1016/j.xphs.2017.11.002
  • Freeze Drying From Organic Co-Solvent Systems, Part 1: Thermal Analysis of
           Co-Solvent-Based Placebo Formulations in the Frozen State
    • Authors: Claudia Kunz; Sonja Schuldt-Lieb, Henning Gieseler
      First page: 887
      Abstract: The use of co-solvent systems has been demonstrated to shorten lengthy freeze drying processes and improve the solubility and stability of certain active pharmaceutical ingredients. The goal of the present study was to evaluate the suitability of two thermal characterization techniques, differential scanning calorimetry and freeze dry microscopy, to identify an optimal co-solvent system. Binary mixtures of a co-solvent (tert-butanol, dimethyl sulfoxide, 1,4-dioxane, acetone or ethanol) and water were investigated.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-10
      DOI: 10.1016/j.xphs.2017.11.003
  • Comparative Assessment of Miniaturized Screening Approaches for Selection
           of Polymers for Amorphous Drug Stabilization
    • Authors: Alamelu Banda; Arushi Manchanda, Wei Zhang, Grace May Alba, Karthik Nagapudi
      First page: 897
      Abstract: The present work highlights the use of miniaturized approaches to screen and prioritize development of solid dispersions that provide stabilization of the amorphous drug against crystallization and enhanced dissolution over the crystalline form. The approaches evaluated include solvent casting and solvent displacement based techniques. Four compounds were evaluated with both these screening approaches. A dual-pH dilution method using FaSSGF and FaSSIF as media was used to evaluate solubility enhancement ratio in each well of the screen.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-16
      DOI: 10.1016/j.xphs.2017.11.006
  • Alternative manufacturing concepts for solid oral dosage forms from drug
           nanosuspensions using fluid dispensing and forced drying technology
    • Authors: Bastian Bonhoeffer; Arno Kwade, Michael Juhnke
      First page: 909
      Abstract: Flexible manufacturing technologies for solid oral dosage forms with a continuous adjustability of the manufactured dose strength, are of interest for applications in personalized medicine. This study explored the feasibility of using micro-valve technology for the manufacturing of different solid oral dosage form concepts. Hard gelatin capsules filled with excipients, placebo tablets and polymer films, placed in hard gelatin capsules after drying, were considered as substrates. For each concept a basic understanding of relevant formulation parameters and their impact on dissolution behavior has been established.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-15
      DOI: 10.1016/j.xphs.2017.11.007
  • Injectable Hydrogels for Localized Chemo- and Radio-Therapy in Brain
    • Authors: Pilar de la Puente; Nicole Fettig, Micah J. Luderer, Abbey Jin, Shruti Shah, Barbara Muz, Vaishali Kapoor, Sreekrishna M. Goddu, Noha Nabil Salama, Christina Tsien, Dinesh Thotala, Kooresh Shoghi, Buck Rogers, Abdel Kareem Azab
      First page: 922
      Abstract: Overall survival of patients with newly diagnosed glioblastoma (GBM) remains dismal at 16 months with state-of-the-art treatment that includes surgical resection, radiation and chemotherapy. GBM tumors are highly heterogeneous and mechanisms for overcoming tumor resistance have not yet fully been elucidated. An injectable chitosan hydrogel capable of releasing chemotherapy (Temozolomide, TMZ) while retaining radioactive isotopes agents (Iodine, 131I) was used as a vehicle for localized radiation and chemotherapy, within the surgical cavity.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-20
  • Environmentally responsive dual-targeting nanoparticles: improving drug
           accumulation in cancer cells as a way of preventing anticancer drug efflux
    • Authors: Cenk Daglioglu
      First page: 934
      Abstract: Drug targeting and stimuli-responsive drug release are two active areas of cancer research and hold tremendous potential in the management of cancer drug resistance. In this study, I addressed this issue and focused on the synthesis and characterization of pH-responsive Fe3O4@SiO2(FITC)-BTN/FA/DOX multifunctional nanoparticles aiming to increase drug accumulation in malignancies with both dual active targeting and endosomal drug release properties. Dye-doped silica magnetic-fluorescent composite was constructed by a simple co-precipitation of Fe+2/Fe+3 salts followed by sol-gel formation and dual-targeting function was obtained by conjugating folate and biotin moieties on the silica surface of nanoparticles via an esterification reaction.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-26
  • A physiologically-based pharmacokinetic modeling approach to predict
           drug-drug interactions of buprenorphine after subcutaneous administration
           of CAM2038 with perpetrators of CYP3A4
    • Authors: Tao Liu; Jogarao V.S. Gobburu
      First page: 942
      Abstract: CAM2038, FluidCrystral (FC) injection depot, is an extended release formulation of buprenorphine given subcutaneously every 1 week (Q1W) or every 4 weeks (Q4W). The purpose of this research is to predict the magnitude of drug-drug interaction (DDI) after coadministration of a strong CYP3A4 inducer or inhibitor using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model was developed for CAM2038 based on the previously published buprenorphine PBPK model after intravenous (IV) and sublingual (SL) administration and the PK profiles after SC administration of CAM2038 from two Phase I clinical trials.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-01
  • Prediction of apparent oral clearance of small-molecule inhibitors in
           pediatric patients
    • Authors: Yoshihiko Kimura; Yugo Chisaki, Tomohiko Saki, Chikako Matsumura, Hideyuki Motohashi, Masahide Onoue, Yoshitaka Yano
      First page: 949
      Abstract: The purpose of this study was to build regression models for the prediction of apparent oral clearance (CL/F) for small-molecule inhibitors in the pediatric population using data obtained from adults. Two approaches were taken; a simple allometric regression model which considers no inter-drug or inter-individual variability and an allometric regression model with mixed-effects modeling (MEM) where some variability parameters are included in the model. Average CL/F values were obtained for 15 drugs at various dosages from 31 literatures (a total of 139 datasets) conducted in adults and for 15 drugs from 26 literatures (62 datasets) conducted in children.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-10
      DOI: 10.1016/j.xphs.2017.11.001
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