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Journal Cover Journal of Pharmaceutical Sciences
  [SJR: 0.984]   [H-I: 130]   [162 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0022-3549 - ISSN (Online) 1520-6017
   Published by Elsevier Homepage  [3089 journals]
  • Editorial Advisory Board
    • Citation: Journal of Pharmaceutical Sciences 107, 1 (2018)
      PubDate: 2018-01
      DOI: 10.1016/S0022-3549(17)30786-4
      Issue No: Vol. 107, No. 1 (2018)
  • 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
  • Manipulating aggregation behaviour of the uncharged peptide carbetocin
    • Authors: Ulrich B. Høgstedt; Jesper Østergaard, Torsten Weiss, Helen Sjögren, Marco van de Weert
      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
  • 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
      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
  • 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
      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
      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
  • Density and Shape Factor Terms in Stokes’ Equation for Aerodynamic
           Behavior of Aerosols
    • Authors: Anthony J. Hickey; David A. Edwards
      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
  • 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
      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
  • 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
      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
  • 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
      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
  • Current Japanese Regulatory Systems for Generics and Biosimilars
    • Authors: Ryosuke Kuribayashi; Kenji Sawanobori
      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
  • “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
      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
  • 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
      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
  • Predictive Screening Tools Used in High Concentration Protein Formulation
    • Authors: Melanie Hofmann; Henning Gieseler
      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
  • 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
      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
  • 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
      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
  • Erratum to “Conversion of Pregabalin to
    • Authors: Amanda M. Drachnik; Harshita Kumari, Collin M. Mayhan, Drew A. Fowler, Wei G. Wycoff, Charles L. Barnes, John E. Adams, Carol A. Deakyne, Jerry L. Atwood
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-27
  • 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
      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
  • Environmentally responsive dual-targeting nanoparticles: improving drug
           accumulation in cancer cells as a way of preventing anticancer drug efflux
    • Authors: Cenk Daglioglu
      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
  • Rapid, Room Temperature Nanoparticle Drying and Low Energy Reconstitution
           via Electrospinning
    • Authors: Shani L. Levit; Ratib M. Stwodah, Christina Tang
      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
  • 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
      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
  • Evaluation of a Biologic Formulation using Customized Design of Experiment
           and Novel Multidimensional Robustness Diagrams
    • Authors: Radhakrishna K. Maroju; Steve Barash, Charlene Brisbane
      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
  • 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
      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
  • 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
      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
  • An Inter-Company Perspective on Biopharmaceutical Drug Product Robustness
    • Authors: Sorina Morar-Mitrica; Monica L. Adams, George Crotts, Christine Wurth, Peter M. Ihnat, Tanvir Tabish, Valentyn Antochshuk, Willow DiLuzio, Daniel Dix, Jason Fernandez, Kapil Gupta, Michael S. Fleming, Bing He, James K. Kranz, Dingjiang Liu, Chakravarthy Narasimhan, Eric Routhier, Kathy Taylor, Nobel Truong, Elaine Stokes
      Abstract: The BioPhorum Development Group (BPDG) is an industry-wide consortium enabling networking and sharing of best practices for the development of biopharmaceuticals. To gain a better understanding of current industry approaches for establishing biopharmaceutical drug product (DP) robustness, the BPDG-Formulation Point Share (FPS) group conducted an inter-company collaboration exercise, which included a bench-marking survey and extensive group discussions around the scope, design, and execution of robustness studies.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-23
  • 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
      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
  • 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
      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
  • Fabrication and Use of PLGA-based Formulations Designed for Modified
           Release of 5-Fluorouracil
    • Authors: Nattawut Leelakanok; Sean Geary, Aliasger Salem
      Abstract: 5-fluorouracil (5-FU) is a chemotherapeutic agent that has been used for the treatment of a variety of malignancies since its initial introduction to the clinic in 1957.1 Due to its short biological half-life, multiple dosings are generally required to maintain effective 5-FU plasma concentrations throughout the therapeutic period. Clinical studies have shown that continuous 5-FU administration is generally superior to bolus injection as exhibited by lower toxicities and increased therapeutic efficacy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-15
  • The Use of a GroEL-BLI Biosensor to Rapidly Assess Pre-Aggregate
           Populations for Antibody Solutions Exhibiting Different Stability Profiles
    • Authors: Samantha E. Pace; Sangeeta B. Joshi, Reza Esfandiary, Robert Stadelman, Steven M. Bishop, C.R. Middaugh, Mark Fisher, David B. Volkin
      Abstract: An automated method using biotinylated GroEL-streptavidin biosensors with Bio-Layer Interferometry (GroEL-BLI) was evaluated to detect the formation of transiently formed, pre-aggregate species in various pharmaceutically relevant monoclonal antibody (mAb) samples. The relative aggregation propensity of various IgG1 and IgG4 mAbs was rank-ordered using the GroEL-BLI biosensor method, and the least stable IgG4 mAb was subjected to different stresses including elevated temperatures, acidic pH, and addition of guanidine-HCl.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-13
  • Determination of non-spherical morphology of doxorubicin-loaded liposomes
           by atomic force microscopy
    • Authors: Naoki Takahashi; Kenjirou Higashi, Keisuke Ueda, Keiji Yamamoto, Kunikazu Moribe
      Abstract: The 3-D morphology of doxorubicin (DOX)-loaded liposomes with a size of ca. 100 nm was characterized by AFM in an aqueous environment. Prolate liposomes appear in accordance with linear expansion of DOX fiber bundles precipitated inside liposomes. Oblate and concave liposomes were simultaneously observed with increased DOX concentrations; however, their morphologies were not readily determined by 2-D cryo-TEM imaging. Precise data analysis of the 3-D parameters of each liposome allowed semi-quantitative evaluation of the transformation of spherical liposomes into non-spherical - prolate, oblate, and concave liposomes.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-13
  • Suitability of the AUC ratio as an indicator of the pharmacokinetic
           advantage in HIPEC
    • Authors: M.I. Mas-Fuster; A. Ramon-Lopez, J. Lacueva, P. Más-Serrano, R. Nalda-Molina
      Abstract: The purpose of this study was to evaluate the area under the concentration time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy (HIPEC).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-13
  • Potential of cationic-polymeric nanoparticles for oral delivery of
           naringenin: In vitro and in vivo investigations
    • Authors: Sundeep Chaurasia; Ravi R. Patel, Prasad Vure, Brahmeshwar Mishra
      Abstract: To improve the bioavailability and anticancer potential of naringenin (NRG) by developing a drug-loaded polymeric nano-delivery system. NRG-loaded eudragit E100 nanoparticle (NRG-EE100-NPs) system was developed, and physicochemically characterized. In vivo pharmacokinetic and in vitro cytotoxicity ability of the NRG-EE100-NPs was investigated. In vivo anticancer activity was evaluated in murine BALB/c mice-bearing colorectal tumor. The NRG-EE100-NPs had an optimum mean particle size (430.42±5.78nm), polydispersity index (0.283±0.089) with percent entrapment efficiency (68.83±3.45%).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-13
  • Antitumor Efficacy and Toxicity of 5-FU-loaded PLGA Pellets
    • Authors: Nattawut Leelakanok; Sean M. Geary, Aliasger K. Salem
      Abstract: The aim of this study was to formulate a biodegradable implant capable of imparting local anti-tumor activity through the sustained release of the chemotherapeutic agent, 5-fluorouracil (5-FU). Thus injectable pellets (< 1.2 mm diameter) made from poly(lactide co-glycolide (PLGA) and loaded with 5-FU at varying drug:polymer ratios were fabricated using hot-melt extrusion and tested for their ability to provide sustained release of 5-FU in in vitro and in vivo settings. In addition, these formulations were compared against soluble 5-FU for their antitumor activity in vivo as well as for their toxicity.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-13
  • Understanding Protein-Interface Interactions of a Fusion Protein at
           Silicone Oil-Water Interface Probed by Sum Frequency Generation
           Vibrational Spectroscopy
    • Authors: Yaoxin Li; Duohai Pan, Vishal Nashine, Smeet Deshmukh, Balvinder Vig, Zhan Chen
      Abstract: Protein adsorbed at the silicone oil-water interface can undergo a conformational change that has the potential to induce protein aggregation upon storage. Characterization of the protein structures at interface is therefore critical for understanding the protein-interface interactions. In this paper, we have applied sum frequency generation (SFG) spectroscopy for studying the secondary structures of a fusion protein at interface and the surfactant effect on protein adsorption to silicone oil-water interface.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-11
      DOI: 10.1016/j.xphs.2017.09.029
  • New polymorph form of dexamethasone acetate
    • Authors: Ronaldo Pedro da Silva; Mateus Felipe Schuchter Ambrósio, Luciana Almeida Piovesan, Maria Clara Ramalho Freitas, Daniel Lima Marques de Aguiar, Bruno Araújo Cautiero Horta, Eugenio Epprecht, Rosane Aguiar da Silva San Gil, Lorenzo do Canto Visentin
      Abstract: A new monohydrated polymorph of dexamethasone acetate (DEX-II) was crystallized and its crystal structure characterized. The different analytical techniques used for describing its structural and vibrational properties were: single crystal (SCXRD) and polycrystal (PXRD) X-ray diffraction, solid state nuclear magnetic resonance (solid-state NMR), infrared spectroscopy (IR). A Hirshfeld surface (HS) analysis was carried out through self-arrangement cemented by H-bonds observed in this new polymorph.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-11
  • DHA and pGPMA Dual Modified pH Sensitive Polymeric Micelles for Target
           Treatment of Liver Cancer
    • Authors: Haojun Ma; Chen Jiang
      Abstract: In clinical therapy, the poor prognosis of hepatocellular carcinoma (HCC) is mainly attributed to the failure of chemotherapeutical agents to accumulate in tumor as well as lack of potency of tumor penetration. In this work, we developed actively tumor-targeting micelles with pH-sensitive linker as a novel nanocarrier for HCC therapy. These micelles comprised of biodegradable PEG-pAsp polymers, in which PTX can be covalently conjugated to pAsp via an acid-labile acetal bond to form pH-responsive structures.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-09
      DOI: 10.1016/j.xphs.2017.09.011
  • Development of a Modified Release Formulation of Lovastatin Targeted to
           Intestinal Methanogens Implicated in Irritable Bowel Syndrome with
    • Authors: Steven Hubert; Alan Chadwick, Vince Wacher, Olivia Coughlin, John Kokai-Kun, Andrew Bristol
      Abstract: There is growing evidence that methane production, predominantly by Methanobrevibacter smithii (M. smithii), in the intestines is a cause of constipation, pain and bloating in irritable bowel syndrome with constipation (IBS-C). M. smithii resides primarily in the large intestine but can also colonize the small intestine. In-vitro studies found that the prodrug lactone form of lovastatin, found in cholesterol lowering drugs, inhibited methane production in stool samples from patients with IBS-C. However, the cholesterol-lowering lovastatin β-hydroxyacid (HA) was ineffective at inhibiting methane production in this system.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.028
  • The use of a 2,2’-azobis (2-amidinopropane) dihydrochloride (AAPH)
           stress model as an indicator of oxidation susceptibility for monoclonal
    • Authors: Michelle Z. Dion; Y. John Wang, Daniel Bregante, Wayman Chan, Nisana Andersen, Amy Hilderbrand, Danielle Leiske, Cleo M. Salisbury
      Abstract: Protein oxidation is a major pathway for degradation of biologic drug products. Past literature reports have suggested that AAPH, a free radical generator that produces alkoxyl and alkyl peroxyl radicals, is a useful model reagent stress for assessing the oxidative susceptibility of proteins. Here, we expand the applications of the AAPH model by pairing it with a rapid peptide map method to enable site-specific studies of oxidative susceptibility of monoclonal antibodies (mAbs) and their derivatives for comparison between formats, the evaluation of formulation components, and comparisons across stress models.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.022
  • In vivo transgene expression in the pancreas by the intraductal injection
           of naked plasmid DNA
    • Authors: Yuma Yamada; Mai Tabata, Jiro Abe, Masatoshi Nomura, Hideyoshi Harashima
      Abstract: Patients with type I diabetes, which is caused by the destruction of pancreatic islets, now require regular therapeutic injections of insulin. The use of transgene therapy represents an alternate and potent strategy for the treatment of type I diabetes. However, only a limited number of studies regarding in vivo gene delivery targeting the pancreas and islets have been reported. Here, we report on the possibility of in vivo transgene expression in the pancreas by the intraductal injection of naked plasmid DNA (pDNA).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.021
  • Drug-Disease Interaction: Effect of inflammation and Nonsteroidal
           Anti-Inflammatory Drugs on Cytochrome P450 Metabolites of Arachidonic Acid
    • Authors: Ali Aghazadeh-Habashi; Waheed Asghar, Fakhreddin Jamali
      Abstract: Inflammatory conditions increase cardiovascular (CV) risk. Some nonsteroidal anti-inflammatory drugs (NSAIDs) that are used to treat pain and inflammation are also associated with CV complications. Inflammation, but not NSAIDs, disrupts the balance of vasodilator and vasoconstrictor components of the renin-angiotensin system (RAS) within the heart. Herein, we report the effect of both inflammation and NSAIDs (rofecoxib, celecoxib and meloxicam) on the physiologically active cytochrome P450 (CYP) metabolites of arachidonic acid (ArA) in the rat with adjuvant arthritis (AA).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.020
  • Optimization of a Vaginal Suppository Formulation to Deliver SHetA2 as a
           Novel Treatment for Cervical Dysplasia
    • Authors: Sanjida Mahjabeen; Manolya K. Hatipoglu, Vishal Chandra, Doris M. Benbrook, Lucila Garcia-Contreras
      Abstract: Cervical dysplasia induced by the human papilloma virus (HPV) unpredictably progresses to cervical cancer. Therapeutic options are invasive and affect the patient’s quality of life. SHetA2 has demonstrated therapeutic efficacy against human and murine HPV- induced tumors, but its oral bioavailability is
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.018
  • Evaluation of Glass Delamination Risk in Pharmaceutical 10 mL/10R Vials
    • Authors: Dominique Ditter; Alejandra Nieto, Hanns-Christian Mahler, Holger Roehl, Michael Wahl, Joerg Huwyler, Andrea Allmendinger
      Abstract: Glass delamination is characterized by the dissociation of glass flakes from the glass surface. Since glass delamination is time dependent, five vial types were investigated to assess delamination under accelerated stress conditions published as quick tests in literature and compared to stress testing recommended per United States Pharmacopoeia (USP). A broad panel of analytical techniques was employed to test the solution for visible/sub-visible particles and leachables, and characterize topography and composition of the surface.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.016
  • How sensitive are transdermal transport predictions by microscopic stratum
           corneum models to geometric and transport parameter input'
    • Authors: Jessica Wen; Soh Myoung Koo, Nancy Lape
      Abstract: While predictive models of transdermal transport have the potential to reduce human and animal testing, microscopic stratum corneum (SC) model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and penetrant transport parameters (e.g. compound diffusivity in lipids). Most microscopic models are limited to a simple rectangular brick-and-mortar SC geometry and do not account for variability across delivery sites, hydration levels, and populations.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.015
  • Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid
           in Post-Extractive Alveolar Wounds
    • Authors: Ovidio Catanzano; Vittoria D’Esposito, Pietro Formisano, Joshua S. Boateng, Fabiana Quaglia
      Abstract: The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a non-satisfactory healing process. Here we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the post-extractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-05
      DOI: 10.1016/j.xphs.2017.09.026
  • Evaluating Suspension Formulations of Theophylline Cocrystals with
           Artificial Sweeteners
    • Authors: Srinivasulu Aitipamula; Annie B.H. Wong, Parijat Kanaujia
      Abstract: Pharmaceutical cocrystals have garnered significant interest as potential solids to address issues associated with formulation development of drug substances. However, studies concerning the understanding of formulation behaviour of cocrystals are still at the nascent stage. We present results of our attempts to evaluate suspension formulations of cocrystals of an anti-asthmatic drug, theophylline, with two artificial sweeteners. Stability, solubility, drug release and taste of the suspension formulations were evaluated.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-05
      DOI: 10.1016/j.xphs.2017.09.013
  • Synthesis, Characterization and Crystal Chemistry of Tasimelteon, a
           Melatonin Agonist, in its Anhydrous and Hemihydrate Forms
    • Authors: Giampiero Ventimiglia; Sonia Bellomi, Giuseppe Barreca, Lorella Giovannelli, Norberto Masciocchi
      Abstract: Two crystalline forms of Tasimelteon, a drug approved by the US FDA for the treatment of non-24-hour sleep-wake disorder, have been studied by single crystal and powder diffraction analyses, TGA, DSC, spectroscopic and optical methods. The synthetic method forming Tasimelteon is described in detail, with its full analytical, spectroscopic and enantiopurity characterization. Solid Tasimelteon hemihydrate, C15H19NO2⋅0.5H2O, is tetragonal with a = b = 7.3573(2) Å, c = 52.062(2) Å, V = 2818.1(2) Å3; Z = 8.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-22
      DOI: 10.1016/j.xphs.2017.09.012
  • Relating observed psychoactive effects to the plasma concentrations of
           delta-9-tetrahydrocannabinol (THC) and its active metabolite: an
           effect-compartment modeling approach
    • Authors: Rakesh Awasthi; Guohua An, Maureen D. Donovan, Laura L. Boles Ponto
      Abstract: The medical use of marijuana is increasing, yet little is known about the exposure-response relationship for its psychoactive effects. It is well known that the plasma concentrations of the principal psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), do not directly correlate to the observed psychoactive effects. The purpose of this research was to use an effect-compartment modeling approach to predict and relate the concentrations of the psychoactive components (THC and its active metabolite) in the “hypothetical” effect-site compartment to the observed psychoactive effects.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-20
      DOI: 10.1016/j.xphs.2017.09.009
  • Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and
           Pluronic Lecithin Organogel
    • Authors: Qian Zhang; Yunmei Song, Stephen W. Page, Sanjay Garg
      Abstract: The transdermal delivery of two fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from two commercially available transdermal bases, pluronic lecithin organogel (PLO) and Lipoderm® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin were evaluated. Retention and depth distribution profiles in skin were obtained by tape-stripping and then followed by optical sectioning using multiphoton microscopy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-18
      DOI: 10.1016/j.xphs.2017.09.008
  • Evidence that P-glycoprotein inhibitor (elacridar)-loaded nanocarriers
           improve epidermal targeting of an anticancer drug via absorptive cutaneous
           transporters inhibition
    • Authors: Daniela V. Giacone; Vanessa F.M. Carvalho, Soraia K.P. Costa, Luciana B. Lopes
      Abstract: Because P-glycoprotein (P-gp) plays an absorptive role in the skin, its pharmacological inhibition represents a strategy to promote cutaneous localization of anticancer agents that serve as its substrates, improving local efficacy while reducing systemic exposure. Here, we evaluated the ability of a nanoemulsion (NE) co-encapsulating a P-gp inhibitor (elacridar) with the antitumor drug paclitaxel to promote epidermal targeting. Loaded NE displayed a nanometric size (45.2±4.0 nm) and negative zeta potential (-4.2±0.8 mV).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-18
      DOI: 10.1016/j.xphs.2017.09.007
  • Manufacture of fibrous dosage forms by wet micro-patterning and drying
    • Authors: Aron H. Blaesi; Nannaji Saka
      Abstract: Recently, we have introduced fibrous dosage forms prepared by the predictable deposition, or 3D-micro-patterning, of a drug-laden fibrous melt on a surface. Such dosage forms enable precisely controlled microstructures and drug release rates, and can be manufactured by an efficient, continuous melt process. However, the applicability of melt-processing to manufacture pharmaceutical dosage forms is limited because the temperatures at which suitable excipients plasticize by melting are greater than the degradation or melting temperatures of many kinds of drugs.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-18
      DOI: 10.1016/j.xphs.2017.08.023
  • Impact of experimental variables on the protein binding of tigecycline in
           human plasma as determined by ultrafiltration
    • Authors: Christoph Dorn; Alexander Kratzer, Uwe Liebchen, Michael Schleibinger, Alexandra Murschhauser, Jens Schlossmann, Frieder Kees, Philipp Simon, Martin G. Kees
      Abstract: Tigecycline, a tetracycline derivative, shows atypical plasma-protein-binding behavior. The unbound fraction decreases with increasing concentration at therapeutic concentrations. Moreover, uncertainty exists about the magnitude of tigecyline’s protein binding in man. Unbound fractions between 2.5 and 35% have been reported in plasma from healthy volunteers, and between 25 and 100 % in patients, respectively. In the present study, the protein binding of tigecycline has been investigated by ultrafiltration using different experimental conditions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-16
      DOI: 10.1016/j.xphs.2017.09.006
  • Mechanics of pharmaceutical pellets – Constitutive properties,
           deformation and breakage behavior∗
    • Authors: Alexander Russell; Rok Šibanc, Rok Dreu, Peter Müller
      Abstract: To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing unit operations (for e.g. withstanding mechanical stresses during coating, optional axial compression, handling, packaging, storage and transport conditions), process design should include consideration of precise limits of accurate micro, macro and bulk properties of the constituent pellets.This communication presents a comprehensive intricate database of micro-mechanical properties’ and breakage probability distribution functions of pellets, illustrating the stiffening and strengthening effects of coatings and the softening and weakening effects of structural moisture.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-16
      DOI: 10.1016/j.xphs.2017.08.022
  • How Predictable are Human Stratum Corneum Lipid/Water Partition
           Coefficients' Assessment and Useful Correlations for Dermal Absorption
    • Authors: Johannes M. Nitsche; Gerald B. Kasting
      Abstract: Partition coefficients between human stratum corneum lipids and water (Ksclip/w) are collected or deduced from a variety of sources in a manner that approximately doubles the available data compared to the current state-of-the-art model [Hansen et al., Adv Drug Deliv Rev 65:252-264 (2013)]. An additional datum for water itself in porcine SC that considerably extends the molecular size and lipophilicity range of the dataset is considered. The data are analyzed in terms of an extended linear free energy relationship involving octanol/water partition coefficients, Abraham solvation parameters and a secondary, power law molecular weight dependence.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-14
      DOI: 10.1016/j.xphs.2017.07.026
  • Editorial
    • Authors: Ronald T. Borchardt
      First page: 1
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-01
  • Professor Samuel H. Yalkowsky: Scientist, Mentor, and Molecular Empath
    • Authors: Paul Myrdal; Ken Morris, Rodolfo Pinal, Neera Jain, Peter Wildfong, George Zografi
      First page: 2
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-22
      DOI: 10.1016/j.xphs.2017.08.010
  • Co-Amorphous API-Small Molecule Mixtures: Considerations in the Choice of
           Co-Formers for Enhancing Dissolution and Oral Bioavailability
    • Authors: Ann Newman; Susan M. Reutzel-Edens, George Zografi
      First page: 5
      Abstract: In recent years, co-amorphous systems, containing an active pharmaceutical ingredient (API) and a small molecule co-former have appeared as alternatives to the use of amorphous solid dispersions containing polymer (ASDs), or co-crystals of API and small molecule co-formers, to improve the dissolution and oral bioavailability of poorly soluble crystalline API. This Commentary considers the relative properties of ASDs and co-amorphous systems in terms of methods of preparation; miscibility; glass transition temperature; physical stability, hygroscopicity; and aqueous dissolution.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.024
  • Physiologically-Based Oral Absorption Modelling to Study Gut-Level Drug
    • Authors: John Chung; Filippos Kesisoglou
      First page: 18
      Abstract: Physiologically-based oral absorption models are in-silico tools primarily used to guide formulation development and project the clinical performance of formulation variants. This commentary briefly discusses additional oral absorption model applications, focusing on gut level drug interactions. Gut level drug interactions can involve drug degradation, metabolic enzymes, transporters, GI motility modulators, acid reducing agents, and food. The growth in publications reporting physiologically-based oral absorption model utilization and successful pharmacokinetic prediction (e.g after acid reducing agent or food co-administration), indicate that oral absorption models have achieved a level of maturity within the industry particularly over the past 15 years.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-25
      DOI: 10.1016/j.xphs.2017.08.015
  • Predicting solubility/miscibility in amorphous dispersions: It’s time to
           move beyond regular solution theories
    • Authors: Bradley D. Anderson
      First page: 24
      Abstract: The evolving challenges associated with the development of poorly soluble drug molecules have been met with major advances in drug solubilization. In particular, amorphous solid dispersion technology is becoming an increasingly important option to enhance oral bioavailability by creating prolonged drug supersaturation to maximize the driving force for intestinal absorption. A primary concern in the development of amorphous solid dispersions is their physical stability, leading to increasing interest in predictive methodologies to assess the propensity for drug crystallization under various storage conditions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-11
      DOI: 10.1016/j.xphs.2017.09.030
  • Industry’s View on Using Quality Control, Biorelevant and Clinically
           Relevant Dissolution Tests for Pharmaceutical Development, Registration
           and Commercialization
    • Authors: Haiyan Grady; David Elder, Gregory K. Webster, Yun Mao, Yiqing Lin, Talia Flanagan, James Mann, Andy Blanchard, Michael J. Cohen, Judy Lin, Filippos Kesisoglou, Andre Hermans, Andreas Abend, Limin Zhang, David Curran
      First page: 34
      Abstract: This paper intends to summarize the current views of the IQ Consortium Dissolution Working Group, which comprises various industry companies, on the roles of dissolution testing throughout pharmaceutical product development, registration, commercialization, and beyond. Over the past 3 decades dissolution testing has evolved from a routine and straightforward test as a component of end-product release into a comprehensive set of tools that the developer can deploy at various stages of the product life cycle.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-23
  • Effect of Water on the Chemical Stability of Amorphous Pharmaceuticals: 2.
           Deamidation of peptides and proteins
    • Authors: Satoshi Ohtake; Shaoxin Feng, Evgenyi Shalaev
      First page: 42
      Abstract: Role of water in chemical (in)stability is revisited, with focus on deamidation in freeze-dried amorphous proteins and peptides. Two distinct patterns for deamidation vs. water have been reported, i.e., a consistent increase in rate constant with water, and a “hockey stick”-type behavior. For the latter, deamidation is essentially independent of water at lower water contents, and accelerates when water content increases above a threshold value. Two simple kinetic models are developed to analyze literature-reported relationships between water content and deamidation rate constants.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-15
      DOI: 10.1016/j.xphs.2017.09.003
  • The Application of Modeling and Prediction to the Formation and Stability
           of Amorphous Solid Dispersions
    • Authors: Kevin DeBoyace; Peter Wildfong
      First page: 57
      Abstract: Amorphous solid dispersion (ASD) formulation development is frequently difficult owing to the inherent physical instability of the amorphous form, and limited understanding of the physical and chemical interactions that translate to initial dispersion formation and long-term physical stability. Formulation development for ASDs has been historically accomplished through trial and error or experience with extant systems, however, rational selection of appropriate excipients is preferred to reduce time to market and decrease costs associated with development.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-04-04
      DOI: 10.1016/j.xphs.2017.03.029
  • Poly(amidoamine) (PAMAM) dendrimers as a pharmaceutical excipient. Are we
           there yet'
    • Authors: Daniel P. Otto; Melgardt M. de Villiers
      First page: 75
      Abstract: Drug solubility could affect the therapeutic use of a drug because the biological activity of a drug is only possible if some fraction of a dissolved drug can permeate and overcome biological membranes to reach its site of action. The solubility-permeation interplay is therefore, probably the most important factor in determining a successful therapeutic outcome of any drug because more than 40% of marketed drugs and more than 70% of pipeline drugs show poor water solubility. Several solubilization techniques are used and include, balancing of pH-pKa properties, employment of cosolvents and the solubilization by host-guest carriers.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-15
  • Automated Supersaturation Stability Assay to Differentiate Poorly Soluble
           Compounds in Drug Discovery
    • Authors: Suzanne M. Skolnik; Gina M. Geraci, Stephanie Dodd
      First page: 84
      Abstract: Increasingly, in vitro assays evaluate a compound’s tendency to maintain supersaturation towards improving oral absorption. Throughput remains a challenge and only small sets of compounds are evaluated in reported studies. The present work describes an automated workflow and data analysis approach to determine supersaturation stability after 16 minutes. Eight increasing concentrations were targeted and supernatant concentration was measured following solvent-shift in FaSSIF. The effect of DMSO on both equilibrium solubility and on induced supersaturation was addressed, while the change in concentration was evaluated over time.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.025
  • Monitoring the Phase Behavior of Supersaturated Solutions of Poorly
           Water-Soluble Drugs Using Fluorescence Techniques
    • Authors: Francesco Tres; Stephen D. Hall, Michael A. Mohutsky, Lynne S. Taylor
      First page: 94
      Abstract: Phase transformations of poorly water-soluble drugs, in low concentration, supersaturated aqueous solutions are of considerable interest. Herein, fluorescence lifetime and steady-state fluorescence spectroscopy were employed to investigate the fluorescence properties of the autofluorescent compound, felodipine (a 1,4-dihydropyridine calcium channel blocker), when present as free drug in solution, drug-rich aggregates and crystals. Measurements were also performed in the absence and presence of liver microsomes.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-11
  • Using potentiometric free drug sensors to determine the free concentration
           of ionisable drugs in colloidal systems
    • Authors: Thuy Tran; Anjan Chakraborty, Xi Xi, Hugo Bohets, Claus Cornett, Konstantin Tsinman, Thomas Rades, Anette Müllertz
      First page: 103
      Abstract: The current study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions and emulsions and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) were selected as model drugs. Self-diffusion nuclear magnetic resonance (NMR) studies were performed and confirmed the entrapment of drugs in micelles in Brij 35 and sodium taurodeoxycholate (TDC)/phosphatidylcholine (PC) micellar solutions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-23
      DOI: 10.1016/j.xphs.2017.05.016
  • Understanding the differences between cocrystal and salt aqueous
    • Authors: Katie L. Cavanagh; Chinmay Maheshwari, Naír Rodríguez-Hornedo
      First page: 113
      Abstract: This work challenges the popular notion that pharmaceutical salts are more soluble than cocrystals. There are cocrystals that are more soluble than salt forms of a drug and vice-versa. It all depends on the interplay between the chemistry of both the solid and solution phases. Aqueous solubility, pHmax, and supersaturation index (SA =SCC or Ssalt/SD) of cocrystals and salts of a basic drug, Lamotrigine (LTG), were determined, and mathematical models that predict the influence of cocrystal/salt Ksp and Ka were derived.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-30
  • Crystalline Polymorphism Emerging from a Milling Induced Amorphous form:
           The Case of Chlorhexidine Dihydrochloride
    • Authors: E. Elisei; J.F. Willart, F. Danède, J. Siepmann, F. Siepmann, M. Descamps
      First page: 121
      Abstract: In this paper, solid state amorphization induced by mechanical milling is shown to be a useful tool to explore the polymorphism of drugs and their mechanism of devitrification. We show in particular how the recrystallization of amorphous chlorhexidine dihydrochloride obtained by milling reveals a complex polymorphism that involves several polymorphic forms. Two new crystalline forms are identified, one of them appearing as a highly disordered precursor state which however clearly differs from the amorphous one.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-14
      DOI: 10.1016/j.xphs.2017.07.003
  • Rifampin Stability and Solution Concentration Enhancement through
           Amorphous Solid Dispersion in Cellulose ω-Carboxyalkanoate Matrices
    • Authors: Hale Çiğdem Arca; Laura I. Mosquera-Giraldo, Junia M. Pereira, Nammalwar Sriranganathan, Lynne S. Taylor, Kevin J. Edgar
      First page: 127
      Abstract: Tuberculosis (TB) is a deadly infectious disease; approximately 2 billion people are currently latently infected with the causative agent Mycobacterium tuberculosis. Approximately 8 million new active cases and 2 million deaths due to TB are recorded annually1. Rifampin (Rif) is a vital first line TB treatment drug. Its effectiveness is hampered by the high dose required (600 mg 1x/day) and by its moderate, variable bioavailability. These issues can be explained by Rif instability at gastric pH, limited solubility at neutral pH, polymorphism, and stimulation of its own metabolism.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-07
      DOI: 10.1016/j.xphs.2017.05.036
  • Formulation Optimization of Freeze-Dried Long-Circulating Liposomes and
           In-Line Monitoring of the Freeze-Drying Process using an NIR Spectroscopy
    • Authors: Bianca Sylvester; Alina Porfire, Pieter-Jan Van bockstal, Sebastian Porav, Marcela Achim, Thomas DE. Beer, Ioan Tomuță
      First page: 139
      Abstract: The effect of lyoprotectant type and concentration on the stability of freeze-dried prednisolone sodium phosphate-loaded long-circulating liposomes (LCL-PLP) was investigated. Trehalose at a 5:1 carbohydrate to lipid molar ratio proved to be superior in maintaining the structural integrity and the permeability properties of the liposome bilayers, assuring the desired characteristics of the final product: a cake with a porous structure and easy to reconstitute, a similar size to the liposomes prior to freeze-drying, a high percent of encapsulated drug and a low residual moisture content.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.024
  • Hot melt extrusion (HME) as solvent-free technique for a continuous
           manufacturing of drug-loaded mesoporous silica
    • Authors: Natalja Genina; Batol Hadi, Korbinian Löbmann
      First page: 149
      Abstract: The aim of the study was to explore hot melt extrusion (HME) as a solvent-free drug loading technique for preparation of stable amorphous solid dispersions (ASD) using mesoporous silica (PSi). Ibuprofen (IBU) and carvedilol (CAR) were used as poorly soluble active pharmaceutical ingredients (APIs). Due to the high friction of a API: PSi mixture below the loading limit of the API, it was necessary to add the polymer Soluplus® (SOL) in order to enable the extrusion process. As a result the APIs distributed between the PSi and SOL phase after HME.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-08
      DOI: 10.1016/j.xphs.2017.05.039
  • Incomplete loading of SLS and FaSSIF micelles within the diffusion layers
           of dispersed drug particles during dissolution
    • Authors: Kendra Galipeau; Michael Socki, Adam Socia, Paul A. Harmon
      First page: 156
      Abstract: Poorly water soluble drug candidates have been common in developmental pipelines over the last several decades. This has fueled considerable research around understanding how bile salt and model micelles can improve drug particle dissolution rates and human drug exposure levels. However, in the pharmaceutical context only a single mechanism of how micelles load solute has been assumed, that being the direct loading mechanism put forth by Cussler1 40 years ago. In this model micelles load at the particle surface and will be loaded to their equilibrium loading values.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-15
      DOI: 10.1016/j.xphs.2017.06.006
  • Stable and Fast-Dissolving Amorphous Drug Composites Preparation via
           Impregnation of Neusilin® UFL2
    • Authors: Mohammad Azad; Jacqueline Moreno, Rajesh Davé
      First page: 170
      Abstract: A promising approach to increase the aqueous solubility, hence the bioavailability, of poorly water-soluble drugs is to convert them into their amorphous state through impregnation into mesoporous silica. Unfortunately, mesoporous silica is not yet available in bulk quantities due to high manufacturing costs. In this work, feasibility of using a commercially available cost-effective mesoporous fine grade Neusilin® UFL2 to prepare amorphous drug composites of two model poorly soluble drugs, Fenofibrate and Itraconazole, is established.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-13
  • Producing Amorphous Solid Dispersions via co-Precipitation and Spray
           Drying: Impact to Physicochemical and Biopharmaceutical Properties
    • Authors: Amanda K.P. Mann; Luke Schenck, Athanas Koynov, Alfred C.F. Rumondor, Xiaoling Jin, Melanie Marota, Chad Dalton
      First page: 183
      Abstract: Many small molecule active pharmaceutical ingredients (APIs) exhibit low aqueous solubility, and benefit from generation of amorphous dispersions of the API and polymer to improve their dissolution properties. Spray drying and hot melt extrusion are two common methods to produce these dispersions; however, for some systems these approaches may not be optimal, and it would be beneficial to have an alternative route. Herein, amorphous solid dispersions of Compound A, a low solubility weak acid, and copovidone were made by conventional spray drying and co-precipitation.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-07-12
      DOI: 10.1016/j.xphs.2017.07.001
  • Gaining Thermodynamic Insight from Distinct Glass Formation Kinetics of
           Structurally Similar Organic Compounds
    • Authors: Arjun Kalra; Paul Luner, Lynne S. Taylor, Stephen R. Byrn, Tonglei Li
      First page: 192
      Abstract: Thermodynamic and kinetic aspects of crystallization of 12 structurally similar organic compounds were investigated from the supercooled liquid state by calorimetric and rheological measurements. Based on their crystallization behaviors, these compounds were divided into three categories: stable glass formers, poor glass formers, and good glass formers with poor stability on reheating. Correlation was sought between thermodynamic quantities and glass formation based on nucleation and crystal growth theories.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-22
      DOI: 10.1016/j.xphs.2017.06.012
  • Transformation of BCS Class I and III Drugs into Ionic Liquids and
           Lipophilic Salts For Enhanced Developability Using Lipid Formulations
    • Authors: Hywel D. Williams; Leigh Ford, Shea Lim, Sifei Han, John Baumann, Hannah Sullivan, David Vodak, Annabel Igonin, Hassan Benameur, Colin W. Pouton, Peter J. Scammells, Christopher J.H. Porter
      First page: 203
      Abstract: Higher lipid solubility of lipophilic salt forms creates new product development opportunities for high-dose liquid-filled capsules. The purpose of this study was to determine if lipophilic salts of BCS Class I amlodipine and BCS Class III fexofenadine, ranitidine and metformin were better lipid formulation candidates than existing commercial salts. Lipophilic salts were prepared from lipophilic anions and commercial HCl or besylate salt forms, as verified by 1H NMR. Thermal properties were assessed by DSC and hot-stage microscopy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-23
      DOI: 10.1016/j.xphs.2017.05.019
  • Process Development and Robust Control of Physical Attributes of an
           Amorphous Drug Substance
    • Authors: Dimitrios Zarkadas; Christopher S. Pridgen, Vincenzo Liotta
      First page: 217
      Abstract: Control of physical attributes of amorphous Active Pharmaceutical Ingredients (APIs) can be challenging due to processability issues, their wide variation during processing and the requirement to control them to specific ranges. In this paper, we report our efforts to develop a robust isolation process for Boceprevir, which delivers specific surface areas between 3.0 and 9.4 m2/g. We developed mechanistic process understanding by utilizing a new method to measure glass transition temperature of API suspensions.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-22
      DOI: 10.1016/j.xphs.2017.09.010
  • Estimation of drug particle size in intact tablets by two dimensional
           X-ray diffractometry
    • Authors: Seema Thakral; Naveen K. Thakral, Raj Suryanarayanan
      First page: 231
      Abstract: The average grain size of a crystalline material can be determined from the γ-profile of Debye rings in two-dimensional X-ray diffraction (2D XRD) frames. Our objectives were to: (i) validate the method for organic powders and use it to determine the grain size in intact tablets, and (ii) demonstrate the pharmaceutical application of this technique by determining the grain size of the active pharmaceutical ingredient (API) in marketed formulations. Six sieve fractions of sucrose were prepared and the particle size distribution was confirmed by laser diffraction.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-09
      DOI: 10.1016/j.xphs.2017.08.021
  • Complexes of felodipine nanoparticles with zein prepared using a dual
           shift technique
    • Authors: Fuzheng Ren; Jinping Fu, Hui Xiong, Lin Cui, Guobin Ren, Haiying Guan, Qiufang Jing
      First page: 239
      Abstract: To improve the dissolution of felodipine, felodipine-zein complexes were prepared using a dual shift technique, with zein as both stabilizer and carrier. The complexes were characterized by particle size, zeta potential, morphology, crystalline properties and release behavior. The complexes could be prepared in high yield and showed good redispersibility. The mean diameters of the felodipine particles in complexes were 150–300 nm, with negative zeta potentials of −30 mV to −25 mV after re-hydration, and the particle sizes of the complexes were in the range 10–80 μm.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-28
      DOI: 10.1016/j.xphs.2017.09.031
  • Assessment of Passive Intestinal Permeability Using an Artificial Membrane
           Insert System
    • Authors: Philippe Berben; Joachim Brouwers, Patrick Augustijns
      First page: 250
      Abstract: Despite reasonable predictive power of current cell-based and cell-free absorption models for the assessment of intestinal drug permeability, high costs and/or lengthy preparation steps hamper their use. The use of a simple artificial membrane (without any lipids present) as intestinal barrier substitute would overcome these hurdles. In the present study, a set of 14 poorly water-soluble drugs, dissolved in two different media [fasted state simulated/human intestinal fluids (FaSSIF/FaHIF)], were applied to the donor compartment of an artificial membrane insert system (AMI-system) containing a regenerated cellulose membrane.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-18
      DOI: 10.1016/j.xphs.2017.08.002
  • Development of a novel amorphous agomelatine formulation with improved
           storage stability and enhanced bioavailability
    • Authors: Panagiotis Barmpalexis; Agni Grypioti, Elisavet Vardaka, Anna Karagianni, Kyriakos Kachrimanis
      First page: 257
      Abstract: The present work describes the development of a novel formulation of amorphous agomelatine (AGM) that exhibits enhanced in vitro dissolution rate and bioavailability, as well as improved storage stability. Agomelatine was loaded on a mixture of microcrystalline cellulose with a high specific surface area excipient, namely colloidal silicon dioxide, employing a wet granulation method and the resultant AGM granules were subsequently formulated into immediate release film-coated tablets. Modulated differential scanning calorimetry (MT-DSC), hot-state light microscopy, powder X-Ray diffraction (PXRD), attenuated total reflection ATR-FTIR and micro-Raman spectroscopy revealed that the API existed primarily in the amorphous state within the prepared formulations, with some crystals of polymorph I also present.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.017
  • Improving the Carprofen Solubility: Synthesis of the Zn2al-Ldh Hybrid
    • Authors: Doretta Capsoni; Irene Quinzeni, Giovanna Bruni, Valeria Friuli, Lauretta Maggi, Marcella Bini
      First page: 267
      Abstract: The development of efficient strategies for drug delivery is considerably desired. Indeed, often several issues such as the drug solubility, the control of the drug release rate, the targeted delivery of drugs, the drug bioavailability and the minimization of secondary effects still present great obstacles. Different methodologies have been proposed, but the use of nano-hybrids compounds that combine organic and inorganic substances seems particularly promising. An interesting inorganic host is the layered double hydroxide (LDH) with a sheets structure and formula M2+1-x M3+x (OH)2](An-)x/n yH2O (M2+= Zn, Mg; M3+=Al; An- = nitrates, carbonates, chlorides).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-05
      DOI: 10.1016/j.xphs.2017.09.019
  • Polymorphism, Intermolecular Interactions, and spectroscopic properties in
           Crystal Structures of Sulfonamides
    • Authors: C. Ignacio Sainz-Díaz; Misaela Francisco-Márquez, Catalina Soriano-Correa
      First page: 273
      Abstract: The antibiotics family of sulfonamides has been used worldwide intensively in human therapeutics and farm livestock during decades. Intermolecular interactions of these sulfamides are important to understand their bioactivity and biodegradation. These interactions are also responsible for their supramolecular structures. The intermolecular interactions in the crystal polymorphs of the sulfonamides, sulfamethoxypyridazine and sulfamethoxydiazine, as models of sulfonamides, have been studied by using quantum mechanical calculations.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-15
  • Hot melt extrudates formulated using design space: one simple process for
           both palatability and dissolution rate improvement
    • Authors: Lorena F.B. Malaquias; Heidi L. Schulte, Juliano A. Chaker, Kapish Karan, Thomas Durig, Ricardo N. Marreto, Tais Gratieri, Guilherme M. Gelfuso, Marcílio Cunha-Filho
      First page: 286
      Abstract: This work aimed to obtain an optimized itraconazole (ITZ) solid oral formulation in terms of palatability and dissolution rate by combining different polymers using hot melt extrusion (HME), according to a simplex centroid mixture design. For this, the polymers Plasdone® (PVP/VA), Klucel ELF® (HPC) and Soluplus® (SOL) were processed using a laboratory HME equipment operating without recirculation at constant temperature. Samples were characterized by physicochemical assays, as well as dissolution rate and palatability using an E-tongue.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-25
      DOI: 10.1016/j.xphs.2017.08.014
  • Estimating the physicochemical properties of poly-substituted aromatic
           compounds using UPPER
    • Authors: Doaa Alantary; Samuel H. Yalkowsky
      First page: 297
      Abstract: The UPPER model (Unified Physicochemical Property Estimation Relationships) has been used to predict nine essential physicochemical properties of pure compounds. It was developed almost 25 years ago and has been validated by the Yalkowsky group for almost 2000 aliphatic, aromatic, and poly-halogenated hydrocarbons. UPPER is based on a group of additive and non-additive descriptors along with a series of well-accepted thermodynamic relationships. In this model, the two-dimensional chemical structure is the only input needed.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-23
  • The combination of GIS and biphasic to better predict in vivo dissolution
           of BCS class IIb drugs, ketoconazole and raloxifene.
    • Authors: Yasuhiro Tsume; Naoto Igawa, Adam J. Drelich, Gregory E. Amidon, Gordon L. Amidon
      First page: 307
      Abstract: The formulation developments and the in vivo assessment of Biopharmaceutical Classification System (BCS) class II drugs are challenging due to their low solubility and high permeability in the human gastrointestinal (GI) tract. Since the GI environment influences the drug dissolution of BCS class II drugs, the human GI characteristics should be incorporated into the in vitro dissolution system to predict bioperformance of BCS class II drugs. An absorptive compartment may be important in dissolution apparatus for BCS class II drugs, especially for bases (BCS IIb) because of high permeability, precipitation and supersaturation.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-15
      DOI: 10.1016/j.xphs.2017.09.002
  • Moisture-induced amorphous phase separation of amorphous solid
           dispersions: molecular mechanism, microstructure, and its impact on
           dissolution performance
    • Authors: Huijun Chen; Yipshu Pui, Chengyu Liu, Zhen Chen, Ching-Chiang Su, Michael Hageman, Munir Hussain, Roy Haskell, Kevin Stefanski, Kimberly Foster, Olafur Gudmundsson, Feng Qian
      First page: 317
      Abstract: Amorphous phase separation (APS) is commonly observed in amorphous solid dispersions (ASD) when exposed to moisture. The objective of this study was to investigate: 1) the phase behavior of amorphous solid dispersions composed of a poorly water-soluble drug with extremely low crystallization propensity, BMS-817399, and PVP, following exposure to different relative humidity (RH), and 2) the impact of phase separation on the intrinsic dissolution rate of amorphous solid dispersion. Drug-polymer interaction was confirmed in ASDs at different drug loading using Infrared (IR) spectroscopy and water vapor sorption analysis.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-26
  • Solubilization of a Poorly Soluble b-RAF (Rapidly Accelerated
           Fibrosarcoma) Inhibitor: From Theory to Application
    • Authors: Linda Bao; Le An, Yingqing Ran
      First page: 327
      Abstract: The oral bioavailability of a drug candidate is influenced by its permeability, metabolism, and physico-chemical properties. Among the physico-chemical properties, solubility and dissolution rate often are the most critical factors affecting the oral bioavailability of a compound. The increasing challenge for the pharmaceutical industry is to achieve reasonable oral bioavailability of poorly water-soluble drug candidates. G-F is a potent and selective b-raf inhibitor with poor water solubility and moderate permeability, which resulted in an absorption-limited exposure in preclinical safety studies.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.023
  • Modeling and Prediction of Drug Dispersability in
    • Authors: Kevin DeBoyace; Ira S. Buckner, Yuchuan Gong, Tzu-chi Rob Ju, Peter L.D. Wildfong
      First page: 334
      Abstract: The expansion of a novel in silico model for the prediction of the dispersability of 18 model compounds with polyvinylpyrrolidone-vinyl acetate copolymer (PVPva) is described. The molecular descriptor R3m (atomic mass weighted 3rd order autocorrelation index) is shown to be predictive of the formation of amorphous solid dispersions at two drug loadings (15% and 75% w/w) using two preparation methods (melt-quenching and solvent evaporation using a rotary evaporator). Co-solidified samples were characterized using a suite of analytical techniques, which included differential scanning calorimetry, powder X-ray diffraction, pair distribution function analysis, polarized light microscopy, and hot stage microscopy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-11
  • In Situ Monitoring and Modeling of the Solution-Mediated Polymorphic
           Transformation of Rifampicin: From Form II to Form I
    • Authors: Nannan Guo; Baohong Hou, Na Wang, Yan Xiao, Jingjing Huang, Yanmei Guo, Shuyi Zong, Hongxun Hao
      First page: 344
      Abstract: In this paper, the solution-mediated polymorphic transformation of rifampicin was investigated and simulated in three solvents at 30 °C. The solid state form I and form II of rifampicin was characterized by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Raman spectroscopy and fourier transform infrared spectroscopy (FTIR). To explore the relative stability, solubility data of form I and form II of rifampicin in butan-1-ol were determined using a dynamical method.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-11
  • Beyond Q1/Q2: The impact of manufacturing conditions and test methods on
           drug release from PLGA-based microparticle depot formulations
    • Authors: John Garner; Sarah Skidmore, Haesun Park, Kinam Park, Stephanie Choi, Yan Wang
      First page: 353
      Abstract: Drug-loaded polymeric microparticles have been used as long-acting injectable (LAI) depot formulations. To obtain FDA approval, a generic LAI depot product needs to be qualitatively (Q1) and quantitatively (Q2) the same in terms of inactive ingredients as its reference listed drug (RLD). However, Q1/Q2 sameness as the RLD does not guarantee the same in vitro drug release profile and in vivo performance, especially when the manufacturing methods are different. There is little consensus on how the in vitro testing needs to be done to examine the release profiles of LAI depot formulations.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-26
  • Enhanced Dissolution of a Porous Carrier-Containing Ternary Amorphous
           Solid Dispersion System Prepared by a Hot Melt Method
    • Authors: Masataka Hanada; Scott V. Jermain, Robert O. Williams
      First page: 362
      Abstract: The focus of our study was to employ a solvent-free, thermal process to evaluate the use of a porous carrier in a drug-polymer-porous carrier ternary formulation containing a high drug load (e.g., ≥50% w/w). The purpose of the study was to improve the dissolution properties of the BCS Class II drug, indomethacin (IND), in the ternary formulation. The effect that the selected polymer has on properties of the formulation was studied, and the formulation characteristics of hypromellose (AF15), copovidone (VA64), and polyvinyl alcohol-polyethylene glycol graft copolymer (KIR) was evaluated in order to understand differences in dissolution rates and drug adsorption onto the porous carrier.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.025
  • Selection of Solid-State Plasticizers as Processing Aids for Hot-Melt
    • Authors: Dipen Desai; Harpreet Sandhu, Navnit Shah, Waseem Malick, Hossein Zia, Wantanee Phuapradit, Siva Ram Kiran Vaka
      First page: 372
      Abstract: The objective of the study was to select solid state plasticizers for hot melt extrusion (HME) process. The physical and mechanical properties of plasticizers, in selected binary (polymer: plasticizer) and ternary (API: polymer: plasticizer) systems, were evaluated to assess their effectiveness as processing aids for HME process. Indomethacin (INM) and Eugradit® E PO were selected as model Active Pharmaceutical Ingredient (API) and polymer, respectively. Solubility parameters, thermal analysis and rheological evaluation were used as assessment tools.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-09-15
      DOI: 10.1016/j.xphs.2017.09.004
  • Mechanistic basis of cocrystal dissolution advantage
    • Authors: Fengjuan Cao; Gordon L. Amidon, Naír Rodríguez-Hornedo, Gregory E. Amidon
      First page: 380
      Abstract: Current interest in cocrystal development resides in the advantages that the cocrystal may have in solubility and dissolution compared to the parent drug. This work provides a mechanistic analysis and comparison of the dissolution behavior of carbamazepine (CBZ) and its two cocrystals, carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) under the influence of pH and micellar solubilization. A simple mathematical equation is derived based on the mass transport analyses to describe the dissolution advantage of cocrystals.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.014
  • Formulation of 3D Printed Tablet for Rapid Drug Release by Fused
           Deposition Modeling (FDM): Screening Polymers for Drug Release,
           Drug-Polymer Miscibility and Printability
    • Authors: Nayan Solanki; Md Tahsin, Ankita Shah, Abu T.M. Serajuddin
      First page: 390
      Abstract: The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling (FDM). Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10 and 20% w/w of haloperidol using Kollidon® VA64, Kollicoat® IR, Affinsiol™15 cP and HPMCAS either individually or as binary blends (Kollidon® VA64+Affinisol™15 cP, 1:1; Kollidon® VA64+HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-21
  • Drug solubilization by means of a surface-modified edible biopolymer
           enabled by hot melt extrusion
    • Authors: Hwee Jing Ong; Rodolfo Pinal
      First page: 402
      Abstract: A formulation/processing combination approach for increasing the solubility of poorly-soluble drugs using solid dispersions (SDs) is presented, whereby the API retains its crystalline state. The approach utilizes a biopolymer naturally produced as dendrimeric nanoparticles that has been surface-modified to act as a solubilizing agent. The solubilizing agent is enabled by hot melt extrusion to produce the SDs. Four APIs, phenytoin (PHT), griseofulvin (GSF), ibuprofen (IBU) and loratadine (LOR) were used as model compounds to evaluate solubility enhancement.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-23
  • Overcoming the Challenges of Low Drug Solubility in the Intravenous
           Formulation of Solithromycin
    • Authors: Daniel Evans; Samuel Yalkowsky, Sara Wu, David Pereira, Prabha Fernandes
      First page: 412
      Abstract: Solithromycin is a fluoro-ketolide (a fourth-generation macrolide) antibiotic that has been undergoing clinical trials for the treatment of community acquired bacterial pneumonia. In this study, development of the tri-amino acid buffered solithromycin intravenous (IV) formulation was performed to minimize the occurrence of infusion associated local adverse events (infusion site pain or phlebitis) observed in patients who received the tartaric acid buffered IV formulation with a lower buffered capacity during Phase I clinical trials.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-28
  • The Selection of a Pharmaceutical Salt – the Effect of the Acidity of
           the Counterion on Its Solubility and Potential Biopharmaceutical
    • Authors: Yan He; Edward Orton, Donglai Yang
      First page: 419
      Abstract: A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. The rationale for the new solid form screening and the criteria for selection are discussed. Prior to the final selection, the pH solubility profiles of the two new salts, a benzoate and a besylate, were compared.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-28
  • Biorelevant Media Slows the Solution-Mediated Phase Transformation of
           Amorphous Spironolactone
    • Authors: Mary S. Kleppe; Roy J. Haskell, Robin H. Bogner
      First page: 426
      Abstract: Solution-mediated phase transformation (SMPT) can reduce the high drug concentration expected from amorphous formulations, eliminating the improvement in drug absorption one hoped to gain from this high energy drug state. The differences in SMPT of a supersaturating system were compared in biorelevant media (Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF)) and USP compendial medium, Simulated Intestinal Fluid without pancreatin (SIFsp). Amorphous spironolactone underwent SMPT to the same hydrate of spironolactone in all three media which was confirmed by the decrease in dissolution rates assessed in a flow-through dissolution apparatus, as well as by the appearance of crystals on the amorphous solid surface detected by polarized light microscopy.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-11-06
  • Albumin-encapsulated liposomes: A novel drug delivery carrier with
           hydrophobic drugs encapsulated in the inner aqueous core
    • Authors: Yuko Okamoto; Kazuaki Taguchi, Keishi Yamasaki, Mina Sakuragi, Shun’ichi Kuroda, Masaki Otagiri
      First page: 436
      Abstract: Liposomes are clinically used in drug delivery, but loading hydrophobic substances is limited to the hydrophobic space of a lipid membrane, despite the fact that it is favorable to encapsulate substances into the inner aqueous core of liposome, from a drug stability of view. We report herein on the preparation of a liposome with bovine serum albumin encapsulated (BSA-liposome). Using this system, it is possible to encapsulate hydrophobic drugs in the inner aqueous core of the liposome based on the hypothesis that the water solubility of hydrophobic drugs is increased when bound to albumin.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-18
      DOI: 10.1016/j.xphs.2017.08.003
  • Amorphous solid dispersion of meloxicam enhanced oral absorption in rats
           with impaired gastric motility
    • Authors: Hiroki Suzuki; Keisuke Yakushiji, Saori Matsunaga, Yukinori Yamauchi, Yoshiki Seto, Hideyuki Sato, Satomi Onoue
      First page: 446
      Abstract: Meloxicam (MEL) shows a slow onset of action in severe pain patients due to delayed gastric motility. This study aimed to develop an amorphous solid dispersion (ASD) of MEL to achieve rapid oral absorption in severe pain patients. ASD formulations of MEL with hydroxypropylmethylcellulose (ASD-MEL/HPMC) and polyacrylates and polymethacrylates (ASD-MEL/EUD) were prepared and physicochemically characterized. Oral absorption behavior of MEL samples was also clarified in both normal and propantheline (PPT)-pretreated rats with impaired gastric motility.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-05-24
      DOI: 10.1016/j.xphs.2017.05.023
  • In vitro-in vivo correlations of carbamazepine nano-dispersions for
           application in formulation development
    • Authors: Zachary Warnken; Michael Puppolo, Justin Hughey, Iris Duarte, Susan Jansen-Varnum
      First page: 453
      Abstract: During formulation development, efficiently integrating in vitro dissolution testing can significantly improve one’s ability to estimate in vivo performance and aide in the selection of premier drug candidates. The concept of in vitro - in vivo relationship/correlation (IVIVR/IVIVC) has garnered significant attention from pharmaceutical scientists to predict expected bioavailability characteristics for drug substances and products. The current work illustrates a comparative evaluation of in vitro tests to access crystalline carbamazepine and various types of amorphous and crystalline dispersions of carbamazepine and Eudragit L100 produced by spray-drying, including a membrane-permeation dissolution methodology and non-sink dissolution.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-15
  • An Investigation of Oral Exposure Variability and Formulation Strategy: A
           Case Study of PI3K-δ Inhibitor and Physiologically Based Pharmacokinetic
           Modeling in Beagle Dogs
    • Authors: Po-Chang Chiang; Jodie Pang, Jia Liu, Laurent Salphati
      First page: 466
      Abstract: It is well acknowledged that drugs with poor aqueous solubility are often associated with poor oral absorption. Fortunately, drugs with a basic pKa can take advantage of solubilization in the stomach under the acidic environment to improve exposure. Consequently, high in vivo variability is often observed when stomach pH is altered. When issue encountered, enabling formulations are often used to solve the problem. However, each enabling formulation has its limitations and the situation can be further complicated by other ADME parameters.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-24
      DOI: 10.1016/j.xphs.2017.06.014
  • Developing quantitative in vitro-in vivo correlation (IVIVC) for
           fenofibrate immediate release formulations with the biphasic
           dissolution-partition test method
    • Authors: Hao Xu; Yi Shi, Socrates Vela, Patrick Marroum, Ping Gao
      First page: 476
      Abstract: This study is to evaluate three fenofibrate formulations including Fournier® 200 mg capsule, Lipidil® 145 mg tablet, and a clinical HME 160 mg tablet by an in vitro biphasic method. Key experimental parameters were evaluated including the selection of biorelevant media, the USP IV flowrate and the USP paddle speed. Varying the hydrodynamic condition resulted in a significant impact on FEN concentration time profiles in both aqueous and octanol phases for these formulations.In vivo pharmacokinetic profiles of the HME tablet, the Lipidil tablet and Fournier capsule under the fasting and low fat fed states are reported.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-27
      DOI: 10.1016/j.xphs.2017.06.018
  • The solubility-permeability trade-off of progesterone with cyclodextrins
           under physiological conditions: Experimental observations and computer
    • Authors: Le Sun; Bing Zhang, Jin Sun
      First page: 488
      Abstract: This study intended to evaluate the effect of cyclodextrins on the apparent solubility and permeability of lipophilic drugs under physiological conditions and establish in silico model to choose the optimal amount of cyclodextrins for cyclodextrin-containing oral formulations. In order to study the effect of cyclodextrins under physiological conditions, bile salts and lecithin were added into the rat intestinal perfusion solution to simulate the fasted intestinal fluid. In addition, the in vivo oral absorption performances of cyclodextrin-containing formulations were simulated by gastrointestinal simulation technology based on the advanced compartmental absorption and transit model (ACAT).
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-13
      DOI: 10.1016/j.xphs.2017.09.032
  • Mechanistic PBPK Modeling of the Dissolution and Food Effect of a BCS IV
           Compound – the Venetoclax Story
    • Authors: Arian Emami Riedmaier; David J. Lindley, Jeffrey A. Hall, Steven Castleberry, Russell T. Slade, Patricia Stuart, Robert A. Carr, Thomas B. Borchardt, Daniel A.J. Bow, Marjoleen Nijsen
      First page: 495
      Abstract: Venetoclax, a selective B-cell lymphoma-2 inhibitor, is a biopharmaceutics classification system (BCS) class IV compound. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model to mechanistically describe absorption and disposition of an amorphous solid dispersion (ASD) formulation of venetoclax in humans.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-10-06
      DOI: 10.1016/j.xphs.2017.09.027
  • Biorelevant drug solubility enhancement modeled by a linear solvation
           energy relationship
    • Authors: Andreas Niederquell; Martin Kuentz
      First page: 503
      Abstract: It is for the pharmaceutical sciences of vital importance to understand how drugs are solubilized in biorelevant media. However, the complexity of fasted state simulated intestinal fluid (FaSSIF) has so far hampered adequate solubility modeling. The present study focuses on apparently neutral compounds at physiological pH and a linear free energy relationship is introduced for biorelevant drug solubilization. Based on literature data of 40 compounds, the Abraham solvation descriptors were calculated from chemical structure to then predict the ratio of solubility enhancement, log(SE) in FaSSIF compared to aqueous buffer solubility at pH 6.5.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-08-29
      DOI: 10.1016/j.xphs.2017.08.017
  • Influence of dissolution media and presence of alcohol on the in vitro
           performance of pharmaceutical products containing an insoluble drug
    • Authors: Valeria Friuli; Lauretta Maggi, Giovanna Bruni, Giorgio Musitelli, Ubaldo Conte
      First page: 507
      Abstract: The purpose of this investigation is to determine how the dissolution media may influence the release rate of an insoluble drug in in-vitro conditions. Some oral dosage forms containing Ibuprofen, a molecule that shows pH-dependent solubility, are tested. They are evaluated in different media to simulate the gastrointestinal transit at paddle rotation speeds of 50 and 100 rpm. Moreover, the potential effect of different ethanol concentrations on drug release is tested. The dissolution profiles of the tablets show a similar behavior in water, pH 1.0 and phosphate buffer pH 4.5 where the two doses are not completely dissolved.
      Citation: Journal of Pharmaceutical Sciences (2017)
      PubDate: 2017-06-14
      DOI: 10.1016/j.xphs.2017.06.001
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