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Journal of Pharmaceutical Sciences

Shenghui Mei, Xingang Li, Xueyun Jiang, Kefu Yu, Song Lin, Zhigang Zhao
The intra- and inter-individual variances of methotrexate (MTX) pharmacokinetics are extremely large, and the pharmacokinetic property of MTX in patients with primary central nervous system lymphoma (PCNSL) is unestablished. A total of 701 MTX plasma concentrations from 98 patients with PCNSL under High-dose methotrexate (HDMTX) therapy were used to develop the population pharmacokinetic (popPK) model of MTX by using the nonlinear mixed-effects modeling method. A two-compartment model was employed to describe the pharmacokinetic property of MTX...
January 10, 2018: Journal of Pharmaceutical Sciences
Kana Horiuchi, Shuichi Ohnishi, Takanobu Matsuzaki, Satoko Funaki, Ayahisa Watanabe, Tohru Mizutare, Sayaka Matsumoto, Kenichi Nezasa, Hiroshi Hasegawa
Accurate prediction of human pharmacokinetics (PK) is important for the choice of promising compounds in humans. As the predictability of human PK by an empirical approach is low for drugs with species-specific PK, the utility of a physiologically based pharmacokinetic (PBPK) model was verified using 16 reference drugs hepatically metabolized. After the prediction method for total clearance (CLtot) and distribution volume at steady state (Vdss) in the conventional PBPK model had been optimized, plasma concentrations following a single oral administration of each reference drug to healthy volunteers were simulated and the prediction accuracy for human PK was compared between empirical approaches and the optimized PBPK model...
January 10, 2018: Journal of Pharmaceutical Sciences
Marie R G Kopp, Paolo Arosio
In the last decades the pharmaceutical market has experienced an increase in the number of therapeutic proteins. The high activity and selectivity of these macromolecules is often achieved at the expense of complex structures, which exhibit several biophysical properties that must be carefully controlled and optimized for the successful development of these drugs as well as for guaranteeing their quality and safety. This need has motivated the application of a variety of biophysical techniques to analyze properties of therapeutic proteins and protein solutions including interactions, aggregation, solubility, viscosity and thermal stability...
January 8, 2018: Journal of Pharmaceutical Sciences
Neeraj J Agrawal, Andrew Dykstra, Jane Yang, Hai Yue, Xichdao Nguyen, Carl Kolvenbach, Nicolas Angell
Methionine oxidation in therapeutic antibodies can impact the product's stability, clinical efficacy and safety and hence it is desirable to address the methionine oxidation liability during antibody discovery and development phase. While the current experimental approaches can identify the oxidation labile methionine residues, their application is limited mostly to the development phase. We demonstrate an in silico method that can be used to predict oxidation labile residues based solely on the antibody sequence and structure information...
January 8, 2018: Journal of Pharmaceutical Sciences
Xue-Qing Chen, Theresa Ziemba, Christine Huang, Ming Chang, Carrie Xu, Jennifer X Qiao, Tammy C Wang, Heather J Finlay, Mark E Salvati, Leonard P Adam, Olafur Gudmundsson, Michael J Hageman
BMS-A is a highly lipophilic compound (clogP 10.5) with poor aqueous solubility (< 0.0001 mg/mL at pH 6.5). The compound exhibits low oral exposure when dosed as cosolvent solution formulations. The purpose of this study was to evaluate lipid-based formulations for enabling high-dose toxicology studies and enhancing toxicology margins of BMS-A in pre-GLP studies in non-rodent species. The solubility of BMS-A was screened in lipid and cosolvent/surfactant excipients and prototype formulations were developed...
January 6, 2018: Journal of Pharmaceutical Sciences
Victoria Díaz-Tomé, Andrea Luaces-Rodríguez, Jesús Silva-Rodríguez, Sara Blanco-Dorado, Laura García-Quintanilla, José Llovo Taboada, José Blanco-Méndez, Michel Herranz, María Gil-Martínez, María Jesús Lamas, Miguel González-Barcia, Francisco J Otero-Espinar, Anxo Fernández-Ferreiro
Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest a-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterised in solution by 1D, 2D-NMR and molecular modelling...
January 3, 2018: Journal of Pharmaceutical Sciences
Lizhen Cheng, Ting Li, Ling Dong, Xiaoyu Wang, Qiye Huo, Haoyu Wang, Zhujun Jang, Xinyu Shan, Weisan Pan, Xinggang Yang
In this study, a bi-layer osmotic pump tablet (OPT) of Flurbiprofen (FP) solid dispersions (SDs) was developed to increase the solubility of the poorly soluble drug and control drug release at a constant rate. Based on the thermodynamic properties investigation of the drug, the carrier and the calculation of the solubility parameters, the FP-SD was prepared by hot melt extrusion (HME) technique with the carrier of PVPVA64. Then central composite design-response surface methodology (CCD-RSM) was used to evaluate the influence of factors on the responses...
December 29, 2017: Journal of Pharmaceutical Sciences
Kazunari Tsujii, Tomoki Hattori, Ayuko Imaoka, Takeshi Akiyoshi, Hisakazu Ohtani
PURPOSE: Fluoropyrimidines, including 5-fluororacil (5-FU), cause gastrointestinal damage in the clinical setting and might affect the gastrointestinal absorption of concomitantly administered drugs. We aimed to evaluate the effects of fluoropyrimidine-induced gastrointestinal damage on the pharmacokinetics and pharmacodynamics of dabigatran etexilate (DABE), an anticoagulant, in rats with gastrointestinal damage induced by the repeated oral administration of 5-FU. METHODS: Rats were administered DABE orally or dabigatran (DAB), an active moiety of DABE, intravenously...
December 29, 2017: Journal of Pharmaceutical Sciences
Hitesh S Purohit, Niraj S Trasi, Dajun D Sun, Edwin C Y Chow, Hong Wen, Xinyuan Zhang, Yi Gao, Lynne S Taylor
Delivering a drug in amorphous form in a formulated product is a strategy used to enhance the apparent solubility of a drug substance and its oral bioavailability. Drug crystallization in such products may occur during the manufacturing process or upon storage, reducing the solubility advantage of the amorphous drug. However, the impact of partial drug crystallization in the drug product on the resulting bioavailability and pharmacokinetics is unknown. In this study, dissolution testing of commercial tacrolimus capsules (which are formulated to contain amorphous drug), both fresh and those containing different amounts of crystalline drug, was conducted using both USP and non-compendial dissolution tests with different dissolution media and volumes...
December 28, 2017: Journal of Pharmaceutical Sciences
Thomas Sandberg, Christian Weinberger, Didem Şen Karaman, Jessica M Rosenholm
The interaction between disulfiram (Antabus®) and silica was studied experimentally by adsorption from apolar solvent onto highly porous silica material (Santa Barbara Amorphous material-3, SBA-3) with large surface area. The adsorption isotherm was fitted to the Langmuir model by accounting two different affinities contributing to the overall behavior, which were attributed to two different types of silanol groups (i.e. geminal and vicinal) present on amorphous silica surfaces. This assumption was supported by theoretical calculations...
December 28, 2017: Journal of Pharmaceutical Sciences
Jacob Atsmon, Irina Cherniakov, Dvora Izgelov, Amnon Hoffman, Abraham J Domb, Lisa Deutsch, Frederic Deutsch, Daphna Heffetz, Hagit Sacks
There is growing clinical interest in developing and commercializing pharmaceutical-grade cannabinoid products, containing primarily tetrahydrocannabinol (THC) and cannabidiol (CBD). The oral bioavailability of THC and CBD is very low due to extensive "first pass" metabolism. A novel oral THC and CBD formulation, PTL401, utilizing an advanced self-emulsifying oral drug delivery system, was designed to circumvent the "first pass" effect. In this study, the bioavailability of THC and CBD from the PTL401 capsule was compared with similar doses from a marketed reference oromucosal spray (Sativex®)...
December 26, 2017: Journal of Pharmaceutical Sciences
Ronald T Borchardt
No abstract text is available yet for this article.
December 26, 2017: Journal of Pharmaceutical Sciences
Ankita V Shah, Abu T M Serajuddin, Robert A Mangione
Gluten is found in food containing wheat, rye and barley, and it may be introduced into medicines through the use of starch or any modified form of starch derived from these grains. The ingestion of gluten poses serious health hazards to people with celiac disease (CD) and non-celiac gluten sensitivity (NCGS), and they must avoid the oral ingestion of gluten. In 2011, the FDA solicited information and public comments on 'gluten in drug products'. However, the 'final rule' that the Agency issued in 2013 involved only the voluntary 'gluten-free' labeling of food, and it did not include drug products...
December 26, 2017: Journal of Pharmaceutical Sciences
Sagar Dugani, Kishor M Wasan, Niranjan Kissoon
No abstract text is available yet for this article.
December 22, 2017: Journal of Pharmaceutical Sciences
Adrian P Defante, Wyatt N Vreeland, Kurt D Benkstein, Dean C Ripple
Nanoparticle tracking analysis (NTA) obtains particle size by analysis of particle diffusion through a time series of micrographs and particle count by a count of imaged particles. The number of observed particles imaged is controlled by the scattering cross-section of the particles and by camera settings such as sensitivity and shutter speed. Appropriate camera settings are defined as those that image, track, and analyze a sufficient number of particles for statistical repeatability. Here, we test if image attributes, features captured within the image itself, can provide measurable guidelines to assess the accuracy for particle size and count measurements using NTA...
December 22, 2017: Journal of Pharmaceutical Sciences
Cesar Calero-Rubio, Ranendu Ghosh, Atul Saluja, Christopher J Roberts
Protein-protein interactions for solutions of an IgG1 molecule were quantified using static light scattering (SLS) measurements from low to high protein concentrations (c2). SLS was used to determine second osmotic virial coefficients (B22) at low c2, and excess Rayleigh profiles (Rex/K vs c2) and zero-q structure factors (Sq=0) as a function of c2 at higher c2 for a series of conditions (pH, sucrose concentration, and total ionic strength (TIS)). Repulsive (attractive) interactions were observed at low TIS (high TIS) for pH 5 and 6...
December 21, 2017: Journal of Pharmaceutical Sciences
Samuel H Yalkowsky, Doaa Alantary
UPPER (Unified Physical Property Estimation Relationships) is a system of empirical and theoretical relationships that relate twenty physicochemical properties of organic molecules to each other and to chemical structure. Melting point is a key parameter in the UPPER Scheme because it is a determinant of several other properties including vapor pressure, and Solubility. This review describes the first principals calculation of the melting points of organic compounds from structure. The calculation is based on the fact that the melting point, Tm, is equal to the ratio of the heat of melting, ΔHm, to the entropy of melting, ΔSm...
December 21, 2017: Journal of Pharmaceutical Sciences
Amadeo B Biter, Sarah Weltje, Elissa M Hudspeth, Christopher A Seid, C Patrick McAtee, Wen-Hsiang Chen, Jeroen B Pollet, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi
Chagas disease due to chronic infection with Trypanosoma cruzi is a neglected cause of heart disease, affecting approximately 6-10 million individuals in Latin America and elsewhere. T. cruzi Tc24, a calcium-binding protein in the flagellar pocket of the parasite, is a candidate antigen for an injectable therapeutic vaccine as an alternative or a complement to chemotherapy. Previously, we reported that a genetically engineered construct from which all cysteine residues had been eliminated (Tc24-C4) yields a recombinant protein with reduced aggregation and improved analytical purity in comparison to the wild-type form, without compromising antigenicity and immunogenicity...
December 21, 2017: Journal of Pharmaceutical Sciences
Tim Ruhl, Gabriele Storti, Norbert Pallua
Fat grafting is a pivotal technique for tissue repair. Adipose stromal cells, including preadipocytes, play a major role in the regenerative effects attributed to fat grafting. But the benefits are impaired by the low survival of the graft due to mechanical stress during harvesting, hypoxia and nutrient deprivation. Non-ionic surfactant molecules demonstrated their efficacy in preventing and repairing mechanical damage on the cellular membrane, but it is poorly understood if and how they affect cellular viability, proliferation and differentiation...
December 21, 2017: Journal of Pharmaceutical Sciences
Honghong Wang, Xingang Li, Shusen Sun, Guifu Mao, Ping Xiao, Chan Fu, Zhuoxin Liang, Min Zheng, Yuling Huang, Haihong Tang, Renhao Ou, Ni Yang, Xi Ling, Zhigang Zhao
An accurate dosage determination is required in neonates when antibiotics are used. The adult data cannot be simply extrapolated to the pediatric population due to significant individual differences. We aimed to identify factors impacting ceftazidime exposure in neonates and to provide drug dosing guidance to clinicians. 43 neonates aged less than 60 days with proven or suspected infections were enrolled in this study. After intravenous administration, blood samples were collected, and plasma ceftazidime concentration was determined using a high-performance liquid chromatography method...
December 21, 2017: Journal of Pharmaceutical Sciences
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