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Journal of Pharmaceutical Sciences

Fatemeh Momenkiaei, Farhad Raofie
Nanoparticles of Curcuma longa Linn (turmeric) rhizome extract were prepared using supercritical carbon dioxide (SC-CO2 ). The SC-CO2 was used for sample pretreatment, including lipophilic compounds removal and extraction as well as particle production. The particle formation process was based on the expansion of supercritical solution (ESS) of plant extract into a secondary chamber. In the course of the ESS process, the herbal extract changed from dissolved mode at higher pressures to precipitated mode at lower pressures, as long as the pressures were higher than critical pressure...
November 12, 2018: Journal of Pharmaceutical Sciences
Arsenii M Pavlov, Alexey S Rzhevskiy, Yuri G Anissimov
In this work drug flux through microporated skin was modeled using detailed numerical solution of the diffusion equation. The results of the modelling were compared to previously published simplified and easy to use analytical equations. Limitations and accuracy of these equations were investigated. Appropriate modifications of the equations were identified to expand them to wider practical applications when pores shape is not circular. Numerical simulations have shown a good accuracy of the new simple equations when these are used within their limits of application...
November 12, 2018: Journal of Pharmaceutical Sciences
Shruthi Vaidhyanathan, Xiaoning Wang, John Crison, Sailesh Varia, Julia Zh Gao, Ajay Saxena, David Good
Sprycel® (Dasatinib) is a BCS II weakly basic drug that exhibits strong pH dependent solubility. Dasatinib is currently presented in two drug product formulations as an adult immediate release tablet and a pediatric powder for oral suspension (PFOS). A bioequivalence study comparing the formulations in adult healthy subjects found overall exposure (AUC0-24 ) from suspension treatments was ∼9-13% lower, Cmax was similar, and median Tmax from PFOS was ∼30 minutes earlier. To understand the mechanism contributing to this behavior a combination of biorelevant dissolution studies and physiologically based pharmacokinetic (PBPK) modeling was used to simulate in vivo performance...
November 12, 2018: Journal of Pharmaceutical Sciences
McKelvey Craig, Kesisoglou Filippos
No abstract text is available yet for this article.
November 12, 2018: Journal of Pharmaceutical Sciences
Amjad Alhalaweh, Ahmad Alzghoul, Christel A S Bergström
In this study, we explore molecular properties of importance in solution-mediated crystallization occurring in supersaturated aqueous drug solutions. Furthermore, we contrast the identified molecular properties with those of importance for crystallization occurring in the solid state. A literature dataset of 54 structurally diverse compounds for which crystallization kinetics from supersaturated aqueous solutions and in melt-quenched solids were reported, was used to identify molecular drivers for crystallization kinetics observed in solution and contrast these to those observed for solids...
November 10, 2018: Journal of Pharmaceutical Sciences
Hongshan Li, Yaning Sun, Jingyu Yu, Chao Liu, Jiang Liu, Yaning Wang
Time varying clearance has been recently recognized in FDA drug labels for oncology monoclonal antibodies (mAbs). Pembrolizumab population CL at steady-state decreased about 20% from the first dose, and individual CL changes varied from 75% decrease to 25% increase, which were correlating with disease conditions. From mechanism of action perspective, this research explored the longitudinal covariate effect on pembrolizumab CL based on data from a Phase II/III clinical trial in patients with non-small cell lung cancer (NSCLC)...
November 10, 2018: Journal of Pharmaceutical Sciences
Tommy Li, Joseph P Balthasar
There is a growing interest in developing inhibitors of the neonatal Fc-receptor, FcRn, for use in the treatment for humoral autoimmune conditions. We have developed a new physiological based pharmacokinetic (PBPK) model that is capable of characterizing the pharmacokinetics and pharmacodynamics (PK/PD) of anti-FcRn monoclonal antibodies (mAb) in mice, rats, and monkeys. The model includes incorporation of FcRn recycling of immune gamma globulin (IgG) in hematopoietic cells in addition to FcRn recycling of IgG in vascular endothelial cells, and considers FcRn turnover and intracellular cycling...
November 10, 2018: Journal of Pharmaceutical Sciences
Atsushi Kambayashi, Jennifer Dressman
The aim of the current research was to develop an in silico oral absorption model coupled with an in vitro dissolution/precipitation testing to predict gastric pH-dependent drug-drug interactions for weakly basic drugs. The effects of elevated gastric pH on the plasma profiles of dipyridamole, prasugrel, and nelfinavir were simulated and compared with pharmacokinetic data reported in humans with or without use of proton pump inhibitors or histamine H2 receptor antagonists. The in vitro dissolution and precipitation data for the weakly basic drugs in biorelevant media were obtained using paddle apparatus...
November 10, 2018: Journal of Pharmaceutical Sciences
Gregory E Amidon, Bradley D Anderson, Joseph P Balthasar, Christel Bergstrom, Shiew-Mei Huang, Gerald Kasting, Filippos Kesisoglou, Johannes Khinast, Donald Mager, Christopher J Roberts, Lian Yu
No abstract text is available yet for this article.
November 10, 2018: Journal of Pharmaceutical Sciences
Tingting Wang, Aaron Markham, Steven J Thomas, Ning Wang, Lihua Huang, Matthew Clemens, Natarajan Rajagopalan
Poloxamer 188 (P188) is a triblock copolymer of the form polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO). The center PPO block is hydrophobic and the side PEO blocks are hydrophilic, resulting in surface-active properties. P188 has been used in the pharmaceutical industry as an excipient in various formulations and drug delivery systems. Although the chemical stability of P188 in the solid state has been reported there are very few reports detailing the solution state stability. In this work, we report the solution state stability of P188 conducted to evaluate the effects of P188 concentration, temperature, pH and buffer type and trace metals on chemical stability...
November 9, 2018: Journal of Pharmaceutical Sciences
Glenn M Ferreira, Cesar Calero-Rubio, Sathish Hasige, Richard L Remmele, Christopher J Roberts
Electrostatically mediated protein-protein interactions (PPI) can influence key product properties such as solubility, solution viscosity, and aggregation rates. Predictive models would allow for candidates / formulations to be screened with little or no protein material. Three monoclonal antibodies (MAbs) that display qualitatively different experimental PPI were evaluated at a range of pH and ionic strength conditions that are typical of product formulations. PPI parameters (kD , B22 , and G22 ) were obtained from static and dynamic light scattering measurements, and spanned from strongly repulsive to strongly attractive net interactions...
November 9, 2018: Journal of Pharmaceutical Sciences
Arrabi Easwaranathan, Beril Inci, Sam Ulrich, Lars Brunken, Violetta Nikiforova, Ulf Norinder, Stephen Swanson, Vesna Munic Kos
Many marketed pharmaceuticals reach extremely high tissue concentrations due to accumulation in lysosomes (lysosomotropism). Quantitative prediction of intracellular concentrations of accumulating drugs is challenging, especially for macrocyclic compounds which mainly do not fit in current in silico models. We tested a unique library of 47 compounds (containing 39 macrocycles) specifically designed to cover the entire range of accumulation intensities observed with pharmaceuticals so far. For the first time, we show that intracellular concentration of compounds measured by LC-MS/MS correlates with the induction of phospholipidosis and inhibition of autophagy, but the highest correlation was observed with the increase of lysosomal volume (R=0...
November 9, 2018: Journal of Pharmaceutical Sciences
Vaibhav Kshirsagar, Serguei Tchessalov, Frank Kanka, Alina Alexeenko
Equipment capability is an important factor in scale up and technology transfer for lyophilized pharmaceutical products. Experimental determination of equipment capability limits, such as the maximum sublimation rate at a given chamber pressure, is time intensive for production lyophilizers. Here we present computational fluid dynamics modeling of equipment capability and compare it with experimental data for Minimum Controllable Pressure ice slab sublimation tests in a 23 m2 shelf area freeze-dryer. It is found that the vapor flow in the production scale is characterized by turbulent effects at high sublimation rates...
November 8, 2018: Journal of Pharmaceutical Sciences
Nan Zheng, Bin Lian, Guobing Xu, Xijuan Liu, Xingang Li, Jiafu Ji
A transit compartment model was widely and successfully applied to characterize the complex time course of cancer chemotherapeutic effects in vivo or in vitro. However the underlying mechanisms were not quantitatively depicted. This study aimed to develop a semi-mechanism based cellular pharmacokinetic/pharmacodynamic (PK/PD) model to characterize paclitaxel (PTX) effect delivered by PLGA-PEG micelles which was based on analysis of drug subcellular distribution, the tubulin assembly level, the cell cycle shift and the resulting cytotoxicity...
November 8, 2018: Journal of Pharmaceutical Sciences
Agnieszka Kozak, Paulina H Marek, Edyta Pindelska
Ethenzamide (ET) was screened in cocrystallization experiments with pharmaceutically acceptable coformer molecules to discover materials of improved physicochemical properties, that is, higher solubility and better stability. Three novel cocrystals of ethenzamide with glutaric, malonic and maleic acids were obtained by neat grinding and slow evaporation from solution. The purpose of the study was to notice the changes in the geometry and interactions of ET molecule in crystalline phase introduced by different acid and relate them to physicochemical properties of pure ethenzamide...
November 8, 2018: Journal of Pharmaceutical Sciences
Olusola Olafuyi, Raj K S Badhan
The insidious nature of Zika virus (ZIKV) infections can have a devastating consequence for foetal development. Recent reports have highlighted that chloroquine (CQ) is capable of inhibiting ZIKV endocytosis in brain cells. We applied pharmacokinetic modelling to develop a predictive model for CQ exposure to identify an optimal maternal/foetal dosing regimen to prevent ZIKV endocytosis in brain cells. Model validation utilised 13 non-pregnancy and 3 pregnancy clinical studies and a therapeutic CQ plasma window of 0...
November 3, 2018: Journal of Pharmaceutical Sciences
Tian-Xiang Xiang, Bradley D Anderson
Hydrogen bonds (HBs) in amorphous solid dispersions (ASDs) may influence physical stability through effects on both drug miscibility and mobility. ASDs containing the HB-donor ibuprofen (IBP) alone or with one of four model polymers (PVP, PVP/VA, PVA or polystyrene (PST)) were monitored by molecular dynamics (MD) simulation. HB distributions and contributions of electrostatic, van der Waals, and internal interactions to miscibility and mobility were analyzed versus drug concentration. The probability of IBP-IBP HBs decreases markedly (0...
November 2, 2018: Journal of Pharmaceutical Sciences
Lea L Sorret, Connor R Monticello, Madison A DeWinter, Daniel K Schwartz, Theodore W Randolph
Silicone oil, used as a lubricating coating in pharmaceutical containers, has been implicated as a cause of therapeutic protein aggregation. After adsorbing to silicone oil-water interfaces, proteins may form interfacial gels, which can be transported into solution as insoluble aggregates if the interfaces are perturbed. Mechanical interfacial perturbation of both monomeric recombinant human interleukin-1 receptor antagonist (rhIL-1ra) and PEGylated rhIL-1ra (PEG rhIL-1ra) in siliconized syringes resulted in losses of soluble monomeric protein...
November 2, 2018: Journal of Pharmaceutical Sciences
Nayan G Solanki, Kyle Lam, Md Tahsin, Suhas G Gumaste, Ankita V Shah, Abu T M Serajuddin
Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has been widely investigated as a carrier for amorphous solid dispersion (ASD) of poorly water-soluble drugs. However, its use has mostly been limited to ASDs prepared by spray drying using organic solvents, and the solvent-free method, hot melt extrusion (HME), has only limited use since it requires high processing temperature where the polymer and drug may degrade. In this investigation, surfactants were used as plasticizers to reduce the processing temperature...
November 2, 2018: Journal of Pharmaceutical Sciences
Sanjaykumar Patel, Wei Zhu, Binfeng Xia, Navneet Sharma, Andre Hermans, Jason D Ehrick, Filippos Kesisoglou, Justin Pennington
Solubility, dissolution, and precipitation in the gastrointestinal tract can be critical for the oral bioavailability of weakly basic drugs. To understand the dissolution/precipitation during the transfer out of the stomach into the intestine, a multicompartment transfer system was developed by modifying a conventional dissolution system. This transfer system included gastric, intestinal, sink/supersaturation, and reservoir compartments. Simulated gastric fluid (SGF) and fasted state simulated intestinal fluid (FaSSIF) were used in the gastric and intestinal compartment respectively to mimic fasted condition...
November 2, 2018: Journal of Pharmaceutical Sciences
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