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Journal of Pharmaceutical Sciences

Yushi Kashihara, Ichiro Ieiri, Takashi Yoshikado, Maeda Kazuya, Masato Fukae, Miyuki Kimura, Takeshi Hirota, Shunji Matsuki, Shin Irie, Noritomo Izumi, Hiroyuki Kusuhara, Yuichi Sugiyama
The aims of this study were (1) to investigate the effects of atorvastatin (10 mg, therapeutic dose) and grapefruit juice (GFJ), inhibitors of OATP2B1, on the pharmacokinetics of substrates for OATP2B1 and BCRP under oral small-dosing conditions (300 μg sulfasalazine, 250 μg rosuvastatin, 300 μg glibenclamide, 1200 μg celiprolol, and 600 μg sumatriptan), and (2) to evaluate the contribution of SLCO2B1*3 and ABCG2 c.421C>A polymorphisms to the pharmacokinetics of the five test drugs in 23 healthy volunteers...
March 17, 2017: Journal of Pharmaceutical Sciences
Upendra A Argikar, Jennifer L Dumouchel, Valerie M Kramlinger, Amanda L Cirello, Mithat Gunduz, Christine E Dunne, Bindi Sohal
Liver is known to be the principal site of drug metabolism. Depending on the route of administration, especially in cases of topical/local delivery, evaluation of local drug metabolism in extrahepatic tissues is vital to assess fraction metabolized. This parameter becomes important from the point of view of drug availability or the contribution to overall clearance. Examples include fraction metabolized in the gut for oral drugs and contribution of pulmonary or renal clearance to total clearance of a drug. Diseases of the eye represent a rising unmet medical need, and a number of therapeutics are currently being developed in the form of small molecules and biologics...
March 17, 2017: Journal of Pharmaceutical Sciences
Takumi Tomono, Kentaro Yano, Takuo Ogihara
Overexpression and/or activation of P-glycoprotein (P-gp), which mediates efflux transport of various anti-cancer drugs in cancer cells, are associated with multi-drug resistance (MDR). On the other hand, malignant cancer cells frequently undergo epithelial-to-mesenchymal transition (EMT), thereby acquiring high migratory mobility and invasive ability. Snail is a transcriptional factor that represses multiple other factors, and its overexpression is a trigger of EMT. Since both P-gp and Snail are involved in malignant evolution of cancer, in this work, we evaluated whether or not EMT induced by overexpression of Snail influences P-gp expression and/or activity...
March 17, 2017: Journal of Pharmaceutical Sciences
Yang Hu, Jaap Rip, Pieter J Gaillard, Elizabeth de Lange, Margareta Hammarlund-Udenaes
The impact of liposomal formulations on the in vivo release and brain delivery of methotrexate (MTX) was quantitatively assessed in rats. Two PEGylated liposomal MTX formulations based on hydrogenated soy phosphatidylcholine (HSPC) or egg-yolk phosphatidylcholine (EYPC) were prepared. The drug release and uptake into the brain after intravenous administration of both formulations were compared with unformulated MTX by determining the released, unbound MTX in brain and plasma using microdialysis. Total MTX concentrations in plasma were determined using regular blood sampling...
March 17, 2017: Journal of Pharmaceutical Sciences
Maria C Paisana, Martin A Wahl, João F Pinto
The potential of PEG, PVP and HPC to inhibit the hydration of olanzapine (OLZ) in aqueous environments was assessed. OLZ Form I (OLZ) suspended in water (A) or in aqueous polymer solutions (2, 0.2, 0.02 and 0.002%) [PEG6,000 (B), PEG40,000 (C), HPC-LF (D) or PVP-K30 (E)]. Filtered samples were analyzed by different techniques (XRPD, FTIR, DSC, (1)H-NMR). OLZ hydration showed to be faster in water than in PEG solutions, regardless of the polymer MW. OLZ in D and E suspensions remained anhydrous at concentrations of 2-0...
March 16, 2017: Journal of Pharmaceutical Sciences
Wei-Jhe Sun, Aktham Aburub, Changquan Calvin Sun
Maintaining good content uniformity (CU) is a significant challenge for low-dose oral tablets in particular when utilizing direct compression. Using six model active pharmaceutical ingredients (APIs), we show that a platform direct compression tablet formulation suitable for developing low dose API with excellent CU can be developed. This platform formulation is enabled by particle engineering, where an API of interest is loaded in a suitable porous carrier to form a uniform API-carrier composite. Powder properties of such composite particles are dictated by the properties of the carrier, which are insensitive to chemical structure and loading level of the API...
March 16, 2017: Journal of Pharmaceutical Sciences
Kei Moriyama, Yukiko Yasuhara, Hiromi Ota
Here we report a simple and direct method to visualize the protonation/deprotonation of an amine API in the solid state using a solid-vapor reaction with propargyl bromide and Raman imaging for the assessment of the API during the manufacturing process of solid formulations. An alkyne tagging occurred on the free-form of solid haloperidol by the vapor phase reaction, and a distinct Raman signal of alkyne was detected. Alkyne signal monitoring by Raman imaging enabled us to visualize the distribution of the free-form haloperidol in a solid formulation...
March 16, 2017: Journal of Pharmaceutical Sciences
Syunsuke Yamamoto, Masatoshi Karashima, Yuta Arai, Kimio Tohyama, Nobuyuki Amano
Although several mathematical models have been reported for the estimation of human plasma concentration profiles of drug substances after dermal application, the successful cases that can predict human pharmacokinetic profiles are limited. Therefore, the aim of this study was to investigate the prediction of human plasma concentrations after dermal application using in vitro permeation parameters obtained from excised human skin. The in vitro skin permeability of seven marketed drug products was evaluated...
March 15, 2017: Journal of Pharmaceutical Sciences
Nao Torimoto-Katori, Ruili Huang, Harutoshi Kato, Rikiya Ohashi, Menghang Xia
The activation of pregnane X receptor (PXR), a member of the nuclear receptor superfamily, can mediate potential drug-drug interactions by regulating the expression of several drug- mediated enzymes and transporters, resulting in reduced therapeutic efficacy or increased toxicity by producing reactive metabolites. Therefore, in the early stage of drug development, it is important to predict these risks using an in silico approach. We constructed a human PXR (hPXR) pharmacophore model based on known structural information of compounds that activate PXR...
March 15, 2017: Journal of Pharmaceutical Sciences
Hiroshi Watanabe, Tadashi Imafuku, Masaki Otagiri, Toru Maruyama
Recent research findings indicate that the posttranslational modification of human serum albumin (HSA) such as oxidation, glycation, truncation, dimerization and carbamylation is related to certain types of diseases. We report herein on a simple and rapid analytical method, using an ESI-TOFMS technique, that allows posttranslational modifications of HSA to be quantitatively and qualitatively evaluated with a high degree of sensitivity. In patients with chronic liver disease, chronic renal disease and diabetes mellitus, an increase in the level of oxidized Cys-34 of HSA accompanied by a decrease in the level of reduced Cys-34 was observed...
March 13, 2017: Journal of Pharmaceutical Sciences
Ariadna Martos, Wendelin Koch, Wim Jiskoot, Klaus Wuchner, Gerhard Winter, Wolfgang Friess, Andrea Hawe
Among many other applications, polysorbates (PS) are used as the most common surfactants in biopharmaceutical products in particular to protect proteins against interfacial stress. Structural heterogeneity, presence of degradants and other impurities, and tendency for degradation are interrelated features found in commercial PS with a direct impact on their functional properties in biopharmaceutical products. These pose a challenge for the analytical characterization of PS at different stages of product development...
March 13, 2017: Journal of Pharmaceutical Sciences
Mostafa Nakach, Jean-René Authelin, Christophe Agut
Stirred media milling is the main technology for producing colloidal nano-crystalline suspensions. A number of studies have been reported on the effect of different operating parameters for lab, pilot, and industrial scales. However, typical milling tool box that can be used to support candidate from selection up to phase III clinical supplies can involve different mill configurations. This paper describes a parametric study and milling kinetic modelling of the different mills. The impact of active pharmaceutical ingredient (API) type and process parameters on milling kinetics was determined...
March 13, 2017: Journal of Pharmaceutical Sciences
Denis Saboti, Uroš Maver, Hak-Kim Chan, Odon Planinšek
Budesonide is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers (MDI), nebulizers and dry powder inhalers (DPI). Inhalable drug particles are conventionally produced by crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations' stability. Other methods involve homogenization or precipitation and often require the use of stabilizers, mostly surfactants...
March 9, 2017: Journal of Pharmaceutical Sciences
M Athar Masood, Josip Blonder, Timothy D Veenstra
Vaccine delivery systems play pivotal role in effective antigen delivery. These systems often contain adjuvants that stimulate specific immune response and are important for vaccines' efficacy and safety. Oil-in-water vaccine delivery lipid emulsion systems containing monophosphoryl lipid A (MPLA) as immune modulator have been extensively investigated in vaccine trials. Herein, we describe a simple orthogonal method, for quantitative measurement of MPLA in an oil-in-water lipid delivery system using direct transesterification reaction followed by gas-chromatography-mass spectrometry (GC-MS) analysis...
March 8, 2017: Journal of Pharmaceutical Sciences
Laura A Wilt, Diana Nguyen, Arthur G Roberts
The P-glycoprotein (Pgp) transporter reduces the penetration of a chemically diverse range of neurotherapeutics at the blood-brain barrier (BBB), but the molecular features of drugs and drug-Pgp interactions that drive transport remain to be clarified. In particular, the triptan neurotherapeutics, eletriptan (ETT) and sumatriptan (STT), were identified to have a greater than 10-fold difference in transport rates despite being from the same drug class. Consistent with these transport differences, ETT activated Pgp-mediated ATP hydrolysis ∼2-fold, while STT slightly inhibited Pgp-mediated ATP hydrolysis by ∼10%...
March 7, 2017: Journal of Pharmaceutical Sciences
Masaki Morishita, Yuki Takahashi, Makiya Nishikawa, Yoshinobu Takakura
Exosomes are small membrane vesicles containing lipids, proteins, and nucleic acids. Recently, researchers have uncovered that exosomes are involved in various biological events, such as tumor growth, metastasis, and the immune response, by delivering their cargos to exosome-receiving cells. Moreover, exosomes are expected to be employed in therapeutic treatments, such as tissue regeneration therapy and antitumor immunotherapy, since exosomes are effective delivery vehicles for proteins, nucleic acids, and other bioactive compounds...
March 7, 2017: Journal of Pharmaceutical Sciences
Rossella Dorati, Antonella De Trizio, Ida Genta, Alessia Merelli, Tiziana Modena, Bice Conti
The aim was to design biodegradable drug delivery systems for gentamicin local delivery, meanwhile acting as scaffold for bone regeneration. Gentamicin loaded thermosetting composite hydrogels (TCHG) were prepared combining chitosan with bovine bone substitutes (BBS Orthoss® granules), beta-glycerophosphate as crosslinker, and lyophilized to obtain composite moldable scaffolds (mCSG). Diverse techniques for gentamicin loading into mCS were investigated by drug incorporation during hydrogel preparation, or drug absorption on preformed mCS...
March 7, 2017: Journal of Pharmaceutical Sciences
Maxx Capece, Zhonghui Huang, Rajesh Davé
In a recent study, it was demonstrated that improving flow of a model poorly flowing and poorly compactable drug substance, acetaminophen, via dry-coating while using fine excipients may promote direct compression. To validate this novel strategy, particularly for high drug loading formulations, this study investigates the effect of microcrystalline cellulose (MCC) particle size and dry-coating on powder tabletability and flowability. It was determined that blends containing fine-sized MCC (20 μm) resulted in the highest tablet tensile strength and best tabletability since it provides higher inter-particle contact area compared to coarser-sized MCC...
March 7, 2017: Journal of Pharmaceutical Sciences
Wim Jiskoot, M Reza Nejadnik, Ahmad S Sediq
No abstract text is available yet for this article.
March 3, 2017: Journal of Pharmaceutical Sciences
Daniel Markl, Parry Wang, Cathy Ridgway, Anssi-Pekka Karttunen, Mousumi Chakraborty, Prince Bawuah, Pertti Pääkkönen, Patrick Gane, Jarkko Ketolainen, Kai Peiponen, J Axel Zeitler
Novel excipients are entering the market to enhance the bioavailability of drug particles by having a high porosity and thus providing a rapid liquid uptake and disintegration to accelerate subsequent drug dissolution. One example of such a novel excipient is functionalised calcium carbonate (FCC), which enables the manufacture of compacts with a bimodal pore size distribution consisting of larger inter-particle and fine intra-particle pores. Five sets of FCC tablets with a target porosity of 45% to 65% were prepared in 5% steps and characterised using terahertz time-domain spectroscopy (THz-TDS) and X- ray computed microtomography (XμCT)...
March 3, 2017: Journal of Pharmaceutical Sciences
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