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Journal of Pharmaceutical Sciences

Steven A Zdravkovic
It has been demonstrated that lyophilized drug formulations have an increased propensity to leach substances from the rubber stoppers comprising their primary packaging system when compared to aqueous liquid formulations stored in the same manner. Unfortunately, patient exposure to leachables originating in lyophilized drug products is not known. To that end, the goal of this study was to assess patient exposure to these leachables after reconstitution, storage, and administration of the lyophilized drug. To achieve this goal, several leachables present in two commercial lyophilized drug products were quantified after contact with PVC and non-PVC medication bags as well as an infusion set for durations of 15 minutes to 7 days at refrigerated and/or ambient temperature...
July 10, 2018: Journal of Pharmaceutical Sciences
Kuo-Ming Yu, Johnson Yiu-Nam Lau, Manson Fok, Yuk-Keung Yeung, Siu-Ping Fok, Tsan-Lin Hu, Yuan-Jang Tsai, Qui-Lim Choo
Treating thrombocytopenia induced by chemotherapy remains an unmet-medical need. The use of recombinant human interleukin-11 (rhIL-11) requires repeated injections and induces significant fluid retention in some patients. Modification of human interleukin-11 with chemically inert polyethylene glycol polymer (PEG) may extend the peripheral circulation half-life leading to an improved pharmacokinetic and pharmadynamic profile. In this study, a number of rhIL-11 PEG conjugates were created to determine the optimal approach to prolong circulating half-life with the most robust pharmacological effect...
July 10, 2018: Journal of Pharmaceutical Sciences
Christina Haeuser, Pierre Goldbach, Joerg Huwyler, Wolfgang Friess, Andrea Allmendinger
Pharmaceutically elegant lyophilisates are highly desirable implying a stable and robust freeze-drying process. In order to ensure homogenous and intact cake appearance after process scale-up and transfer, characterization of lyophilisates during formulation and cycle development is required. The present study investigates different imaging techniques to characterize lyophilisates on different levels. Cake appearance of freeze-dried BSA formulations with different dextran/sucrose ratios was studied by visual inspection, 3D laser scanning, polydimethylsiloxane (PDMS) embedding, scanning electron microscopy (SEM), and micro-computed tomography (μ-CT)...
July 10, 2018: Journal of Pharmaceutical Sciences
Analía Simonazzi, Carolina Davies, Alicia G Cid, Elio Gonzo, Luis Parada, José M Bermúdez
Benznidazole, the first line drug for Chagas disease treatment, presents a low solubility, limiting the possibilities for its formulation. In this work, solid dispersions´ technology was exploited to increase benznidazole kinetic solubility and dissolution rate, seeking for an improvement in its bioperformance. A physical mixture (PM) and a solid dispersion (SD) using Poloxamer 407 as carrier were prepared and characterized. Dissolution tests were performed and data were analyzed with the lumped model, which allowed to calculate different parameters of pharmaceutical relevance...
July 10, 2018: Journal of Pharmaceutical Sciences
Xia Zhang, Chang Wang, Ling Zhou, Wenchao Yang, Lina Zhou, Ying Bao, Meijing Zhang, Baohong Hou, Zhao Xu, Qiuxiang Yin
The solvate formation of sulfadiazine was systematically studied in the four selected solvents with the aids of experiment and simulation methods. The intermolecular interactions between solute and solvent molecules in different solid states were analyzed and compared through their single crystal structures, and the solution behavior of sulfadiazine was discussed using molecular dynamics simulations. The results indicated that sulfadiazine was easy to form solvates with the solvents having strong hydrogen bond acceptor ability, which determined the formation of hydrogen bonding synthon...
July 10, 2018: Journal of Pharmaceutical Sciences
Grzegorz Kijanka, Jared S Bee, Samuel A Korman, Yuling Wu, Lorin K Roskos, Mark A Schenerman, Bram Slütter, Wim Jiskoot
Protein aggregates are one of several risk factors for undesired immunogenicity of biopharmaceuticals. However, it remains unclear which features determine whether aggregates will trigger an unwanted immune response. The aim of this study was to determine the effect of aggregates' size on their relative immunogenicity. A monoclonal murine IgG1 was stressed by exposure to low pH and elevated temperature followed by stirring to obtain aggregates widely differing in size. Aggregate fractions enriched in soluble oligomers, submicron size particles and micron size particles were isolated via centrifugation or size-exclusion chromatography and characterized physicochemically...
July 9, 2018: Journal of Pharmaceutical Sciences
Xiangmin Liao, Ninglin Zhou
A hydrate of co-crystal of Piracetam and 3,5-dihydroxybenzoic acid (35DHBA) was obtained via crystallization from water. Single crystal X-ray data shows that Piracetam/3,5-dihydroxybenzoic acid tetrahydrate (P35TH) crystallizes in the triclinic system with a P1 space group. The physicochemical properties of co-crystal hydrate were characterized using powder X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetric analyzer (TGA) and Fourier Transform Infrared spectroscopy (FTIR)...
June 30, 2018: Journal of Pharmaceutical Sciences
Michał Romański, Ulrich Girreser, Artur Teżyk, Franciszek K Główka
(2S,3S)-1,2:3,4-diepoxybutane (DEB) cross-links DNA guanines by forming the intermediate epoxy-adduct (EHBG). This process is presently considered a primary mechanism for the action of treosulfan (TREO), the prodrug that transforms to DEB via the monoepoxide intermediate EBDM. In this paper, the N-7-guanine adduct of EBDM (HMSBG) was synthesized for the first time and its stability was investigated at physiological in vitro conditions. To synthesize HMSBG, EBDM, formed in-situ from TREO, was treated with guanosine in glacial acetic acid at 60 o C followed by ribose cleavage in 1 M HCl at 80 o C...
June 27, 2018: Journal of Pharmaceutical Sciences
Ayumi Matsuda, Masahiro Mimura, Takuya Maruyama, Takaaki Kurinomaru, Mieda Shiuhei, Kentaro Shiraki
The formulation of high-concentration protein solutions is a challenging issue for achieving subcutaneous administration. Previously, we developed a method of precipitation-redissolution using polyelectrolyte as a precipitant to produce protein solutions at high concentrations. However, the redissolution yield of proteins was insufficient. This study aims to optimize the solution conditions for practical applications by combining immunoglobulin G (IgG) and poly-L-(glutamic acid) (polyE). A systematic analysis of solution pH and polyE size conditions revealed that an acidic condition favors precipitation, while neutral pH values are more effective for the redissolution...
June 27, 2018: Journal of Pharmaceutical Sciences
Chengcheng Zhang, Kortney M Kersten, Jeff W Kampf, Adam J Matzger
The crystal structure of indinavir sulfate, a pharmaceutical administered as an ethanol solvate, is presented, revealing a unique channel/ionic solvate structure to be characteristic of the compound. The properties of the material with regard to thermal treatment and water adsorption follow closely from the structure. The in situ amorphization of the pharmaceutical upon contacting liquid water is observed and highlights the unique dissolution enhancement of marketing the crystalline solvate dosage. Through survey of published crystal structures, an ambiguous sulfate/bisulfate ionization state is also observed in the crystal, which challenges the general understanding of the pharmaceutical...
June 27, 2018: Journal of Pharmaceutical Sciences
Ramon Oliveira Souza, Tadeu Henrique de Lima, Rodrigo Lambert Oréfice, Marcelo Gonzaga de Freitas Araújo, Sandra Aparecida de Lima Moura, Juliana Teixeira Magalhães, Gisele Rodrigues da Silva
Vulvovaginal candidiasis is an inflammation localized in the vulvovaginal area. It is mostly caused by Candida albicans. Its treatment is based on the systemic and/or local administration of antifungal drugs. However, this conventional therapy can fail owing to the resistance of the Candida species and noncompliance of patients. Amphotericin B-loaded PLGA nanofibers are single-use, antifungal, controlled drug delivery systems, and represent an alternative therapeutic scheme for the local treatment of vulvovaginal candidiasis...
June 22, 2018: Journal of Pharmaceutical Sciences
Peng Yu, Dale Eric Wurster
In the current study, the interaction between phenobarbital and activated carbons which is driven by hydrophobic bonding was evaluated. The Two-Mechanism Langmuir-Like Equation (TMLLE) was proposed to describe the isotherms for phenobarbital adsorbing to activated carbons. The parameters in the TMLLE obtained from the non-linear fitting of isotherms were used in the calculations of the differential Gibbs free energy for the hydrophobic bonding-driven interaction. Two thermodynamic models, the Modified Crisp Model and the van't Hoff Equation, were adopted to estimate the differential Gibbs free energy...
June 22, 2018: Journal of Pharmaceutical Sciences
Liang Fang, Ranjana Singh, Lloyd Waxman, Cathy Zhao
Hansen Solubility Parameters (HSP) theory has been successful in explaining the wettability of organic solvents on polymer surfaces and miscibility of different polymers.1 Here, we demonstrate that the amount of bovine serum albumin (BSA) protein adsorption on different polymer surfaces can also be explained by HSP. Interestingly, the HSP of the adsorbed BSA proteins calculated from the protein adsorption data is different than the HSP of native BSA protein itself. The HSP of the adsorbed BSA proteins are more hydrophobic than the native BSA protein...
June 22, 2018: Journal of Pharmaceutical Sciences
A Lehmann, D R Katerere, J Dressman
To assess drug quality and pharmaceutical care in South Africa, "mystery" (i.e. anonymous) customers collected 316 samples from July to September 2016. Solid dosage forms containing amoxicillin alone or in combination with clavulanic acid as well as analgesics containing paracetamol alone or in combination were sampled in a randomized fashion from the formal market (pharmacies) and by convenient sampling from the informal market. Visual inspection, uniformity of dosage units and dissolution testing were performed using validated methods to evaluate adherence to pharmacopoeial quality standards and to identify counterfeit, degraded or substandard drugs...
June 21, 2018: Journal of Pharmaceutical Sciences
Ankush Sharma, Amit K Goyal, Goutam Rath
The objective of the present study is to improve iron bioavailability using high density gastroretentive pellets of zero valent iron nanoparticles (ZVINps). ZVINps were prepared by the chemical reduction method and were characterized for surface morphology, surface charge and thermal properties. High density gastro retentive pellets of iron nanoparticles were prepared using spheronization technique. Pellets were characterized for its micromeritic properties, in vitro drug release and ex-vivo permeability. The pharmacokinetics parameters, organ distribution and toxicity of the optimised pellets were investigated in Wistar rats...
June 21, 2018: Journal of Pharmaceutical Sciences
Hye Lim Lee, Sung Chul Hwang, Jae Woon Nah, Jungsoo Kim, Byungyoul Cha, Dae Hwan Kang, Young-Il Jeong
Redox-responsive nanoparticles having a diselenide linkage were synthesized to target pulmonary metastasis of cancer cells. Methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) was crosslinked using selenocystine-acetyl histidine (Ac-histidine) conjugates (ChitoPEGse) for stimuli-responsive delivery of piperlongumine (PL). ChitoPEGse nanoparticles swelled in an acidic environment and became partially disintegrated in the presence of H2 O2 , resulting in an increase of particle size and in a size distribution having multimodal pattern...
June 21, 2018: Journal of Pharmaceutical Sciences
Rodrigo Cristofoletti, Malcolm Rowland, Lawrence J Lesko, Henning Blume, Amin Rostami-Hodjegan, Jennifer B Dressman
The growth in the utilization of systems thinking principles has created a paradigm shift in the regulatory sciences and drug product development. Instead of relying extensively on end product testing and one-size-fits-all regulatory criteria, this new paradigm has focused on building quality into the product by design as well as fostering the development of product-specific, clinically relevant specifications. In this context, this commentary describes the evolution of bioequivalence regulations up to the current days and discusses the potential of applying a Bayesian-like approach, considering all relevant prior knowledge, to guide regulatory bioequivalence decisions in a patient-centric environment...
June 20, 2018: Journal of Pharmaceutical Sciences
Yi Yang, Anna Mah, Inn H Yuk, Parbir S Grewal, Abigail Pynn, Will Cole, Di Gao, Fan Zhang, Jia Chen, Lynn Gennaro, Christian Schöneich
Protein carbonylation is a post-translational modification referring to the occurrence of aldehydes and ketones in proteins. The current understanding of how carbonylation, in particular, metal-catalyzed carbonylation, occurs in recombinant monoclonal antibodies (mAbs) during production and storage is very limited. To facilitate investigations into mAb carbonylation, we developed a protein carbonylation assay with improved assay robustness and precision over the conventional assays. We applied this assay to investigate mAb carbonylation under production, storage, and stress conditions, and showed that iron, hydrogen peroxide, and polysorbate 20 at pharmaceutically relevant levels critically influence the extent of mAb carbonylation...
June 20, 2018: Journal of Pharmaceutical Sciences
Ana Simões, Francisco Veiga, Carla Vitorino, Ana Figueiras
The pharmaceutical industry has entered in a new era, as there is a growing interest in increasing the quality standards of dosage forms, through the implementation of more structured development and manufacturing approaches. For many decades, the manufacturing of drug products was controlled by a regulatory framework to guarantee the quality of the final product through a fixed process and exhaustive testing. Limitations related to the Quality by Test (QbT) system have been widely acknowledged. The emergence of Quality by Design (QbD) as a systematic and risk-based approach introduced a new quality concept based on a good understanding of how raw materials and process parameters influence the final quality profile...
June 20, 2018: Journal of Pharmaceutical Sciences
Zhi Li, Junya Zhang, Xiao Li, Xinhong Guo, Zhenzhong Zhang
The Fe3O4@C @NaYF4:Yb,Er nano-carriers with multifunctional were synthesized. The mitoxantrone (MTO) were selected as model drug and these nanoparticles have high drug loading (0.63mg/mg). The temperature of Fe3O4@C @NaYF4:Yb,Er in water approached 60°C with 808nm irritation(2.5W/cm2). The cumulative release of these nano drug carriers significantly increased because of temperature increasing, and the 4T1 cells growth inhibition rates were 59.15%, almost 2.25-fold higher than MTO group (p<0.05). Since the nanoparticles had auto-fluorescence under 808nm irritation, the nano-carries could be traced both in vitro and in vivo studies...
June 20, 2018: Journal of Pharmaceutical Sciences
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