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Brenda Espíndola, Francieli Furlan Bortolon, Juliana Munari Oliveira Pinto, Bianca Ramos Pezzini, Hellen Karine Stulzer
The USP Apparatus 3 is a compendial dissolution Apparatus that has been mainly used to assess the performance of modified-release drug products. However, this Apparatus can be applied to dissolution testing of immediate-release tablets as well, with several advantages such as lower consumption of dissolution media, reduced setup time in quality control routine, and minimized hydrodynamic issues. In this work, three immediate-release (IR) tablets containing antihypertensive drugs of different Biopharmaceutic Classification System (BCS) classes were evaluated in order to assess the possible interchangeability between the official dissolution method using typical USP Apparatus 1 or 2 and the proposed methods using USP Apparatus 3...
June 22, 2018: AAPS PharmSciTech
Lucija Vuletić, M Zahirul I Khan, Drago Špoljarić, Maja Radić, Biserka Cetina-Čižmek, Jelena Filipović-Grčić
PURPOSE: The aim of the present work was to classify metaxalone according to the Biopharmaceutics Classification System (BCS), to develop a clinically relevant dissolution method that can be used to predict the oral absorption of metaxalone and to establish an in vitro-in vivo correlation (IVIVC). METHODS: Solubility of the drug was studied in different pH media and permeability studies were performed using a Caco-2 cell model. The in vitro dissolution and in vivo disposition of metaxalone from 3 different immediate release (IR) tablet formulations were investigated using USP 2 apparatus and a single dose, four-way, crossover bioequivalence study in healthy humans along with an oral solution of the drug, respectively...
June 22, 2018: Pharmaceutical Research
Hirra Hussain, David I Fisher, Robert G Roth, W Mark Abbott, Manuel Alejandro Carballo-Amador, Jim Warwicker, Alan J Dickson
Due in part to the needs of the biopharmaceutical industry, there has been an increased drive to generate high quality recombinant proteins in large amounts. However, achieving high yields can be a challenge as the novelty and increased complexity of new targets often makes them 'difficult-to-express'. This study aimed to define the molecular features that restrict the production of a model 'difficult-to-express' recombinant protein, Tissue Inhibitor Metalloproteinase-3 (TIMP-3). Building from experimental data, computational approaches were used to rationalise the re-design of this recombinant target to generate a chimera with enhanced secretion...
June 22, 2018: FEBS Letters
Maria Julia Mora, R Onnainty, Gladys Ester Granero
Biopharmaceutics classification systems based on properties of solubility and permeability or extension of metabolism are very important tools in the early stages of development and regulatory stages of new products. However, until now there is no clear understanding between the interplay among these classification systems. Therefore, the main objective of this work was to make a comparison of concepts of BCS and BDDCS to understand what are the key factors that allowing the integration of these biopharmaceutics classification systems...
June 21, 2018: Molecular Pharmaceutics
David E Wamble, Michael Ciarametaro, Robert Dubois
BACKGROUND: Developments in diagnostics, medical devices, procedures, and prescription drugs have increased life expectancy and quality of life after diagnosis for many diseases. Previous research has shown that, overall, increased investment in medical technology has led to increased health outcomes. In addition, the value of investment in specific innovations, particularly in new pharmaceuticals or biopharmaceuticals, has frequently been shown through an evaluation of the associated health outcomes and costs...
June 21, 2018: Journal of Managed Care & Specialty Pharmacy
Carolina Aloisio, Micaela Ponce-Ponte, Gladys E Granero, Marcela R Longhi
The aim of this work was to predict the permeability of two model drugs, sulfamerazine (SMR) and indomethacin (INM), and to determine the effect on their apparent permeabilities by complexation with cyclodextrins and/or meglumine or incorporation in microemulsions. Permeation experiments were performed using two-chamber diffusion cells with a new composition of bio-mimetic membrane composed of 80% of Lipoid® S100 and 20% of cholesterol in n-octanol 10% w/w solution, at 37 ± 0.5°C and 14,000 rpm. The predictive capacity of the permeability of passive diffusion absorbed compounds was evaluated using 20 drug standards and showed an exponential correlation between the apparent permeability coefficients (Papp ) and the fraction absorbed percentages in humans (Fa%), with an R2 value of 0...
June 19, 2018: AAPS PharmSciTech
Daniel Bojar, Leo Scheller, Ghislaine Charpin-El Hamri, Mingqi Xie, Martin Fussenegger
Programming cellular behavior using trigger-inducible gene switches is integral to synthetic biology. Although significant progress has been achieved in trigger-induced transgene expression, side-effect-free remote control of transgenes continues to challenge cell-based therapies. Here, utilizing a caffeine-binding single-domain antibody we establish a caffeine-inducible protein dimerization system, enabling synthetic transcription factors and cell-surface receptors that enable transgene expression in response to physiologically relevant concentrations of caffeine generated by routine intake of beverages such as tea and coffee...
June 19, 2018: Nature Communications
Suzana A Giffin, Richa Shah, Allison Soloff, Anna Markel Vaysman, Jane Oreper, Andrew Gažo, Pooja Gandhi, Ina Shah, Thomas Malieckal, Daniel Boulos, Teresa Flowers, Carolle A Stevens, Michael S Rocco, Aarti S Patel, Dominick Albano
BACKGROUND: Over the past decade, biopharmaceutical companies have been progressively establishing global frameworks across their capabilities. It is well recognized that the Medical Information (MI) department is a key externally facing function that needs to maintain a consistent focus on optimizing its capabilities of addressing product medical inquiries worldwide. METHODS: In the United States, a consortium named Pharma Collaboration for Transparent Medical Information, phactMI, a collaboration of pharmaceutical company MI departments dedicated to supporting health care professionals in their commitment to provide quality patient care, has provided a forum to benchmark and share best practices across the companies...
January 1, 2018: Therapeutic Innovation & Regulatory Science
Hamdy Abdelkader, Zeinab Fathalla
BACKGROUND: The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need. PURPOSE: In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed. METHODS: Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability...
June 18, 2018: Pharmaceutical Research
Yusra Rahman, Shumaila Afrin, Mohammad Tabish
Studying the interaction of therapeutic molecules with serum albumin is important to understand their biopharmaceutics, pharmacokinetics and toxicity as well as their relation with the structure and function of protein. The biomolecular interaction of an anti-spasmodic drug, pirenzepine with bovine serum albumin (BSA) was investigated using multi-spectroscopic, calorimetric and docking studies. Fluorescence quenching of BSA on interaction with pirenzepine revealed the static mode of quenching. Pirenzepine exhibited a moderate binding to serum albumin with the binding constant value in the order of 104  M-1 ...
June 13, 2018: Archives of Biochemistry and Biophysics
Christophe Tistaert, Tycho Heimbach, Binfeng Xia, Neil Parrott, Tanay Samant, Filippos Kesisoglou
Food can alter the absorption of orally administered drugs. Biopharmaceutics physiologically based pharmacokinetic (PBPK) modeling offers the possibility to simulate a compound's pharmacokinetics under fasted or fed states. To advance the utility of PBPK modeling, with a view to regulatory impact, we have pooled our experience across four pharmaceutical companies to propose a general multi-step PBPK workflow leveraging pre-existing clinical data for immediate release formulations of BCS I and BCS II compounds...
June 12, 2018: Journal of Pharmaceutical Sciences
Hardi Jogi, Rahul Maheshwari, Nidhi Raval, Kaushik Kuche, Vishakha Tambe, Kit-Kay Mak, Mallikarjuna Rao Pichika, Rakesh Kumar Tekade
Cancer is estimated to be a significant health problem of the 21st century. The situation gets even tougher when it comes to its treatment using chemotherapy employing synthetic anticancer molecules with numerous side effects. Recently, there has been a paradigm shift toward the adoption of herbal drugs for the treatment of cancer. In this context, a suitable delivery system is principally warranted to deliver these herbal biomolecules specifically at the tumorous site. To achieve this goal, carbon nanotubes (CNTs) have been widely explored to deliver anticancer herbal molecules with improved therapeutic efficacy and safety...
June 15, 2018: Nanomedicine
Jean-Étienne R L Morlighem, Chen Huang, Qiwen Liao, Paula Braga Gomes, Carlos Daniel Pérez, Álvaro Rossan de Brandão Prieto-da-Silva, Simon Ming-Yuen Lee, Gandhi Rádis-Baptista
Marine invertebrates, such as sponges, tunicates and cnidarians (zoantharians and scleractinian corals), form functional assemblages, known as holobionts, with numerous microbes. This type of species-specific symbiotic association can be a repository of myriad valuable low molecular weight organic compounds, bioactive peptides and enzymes. The zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa) is one such example of a marine holobiont that inhabits the coastal reefs of the tropical Atlantic coast and is an interesting source of secondary metabolites and biologically active polypeptides...
June 13, 2018: Marine Drugs
Cheng Zhang, Maariyah Samad, Haoran Yu, Nesrine Chakroun, David Hilton, Paul A Dalby
Computationally-guided semi-rational design has significant potential for improving the aggregation kinetics of protein biopharmaceuticals. While improvement in the global conformational stability can stabilise proteins to aggregation under some conditions, previous studies suggest that such an approach is limited because thermal transition temperatures (Tm) and the fraction of protein unfolded (fT) tend to only correlate with aggregation kinetics where the protein is incubated at temperatures approaching the Tm...
June 13, 2018: Molecular Pharmaceutics
Carolin Richter, Cornelia Lipperheide, Uwe Lipke, Alf Lamprecht
Commercially available, uncoated elastomeric closures were examined in regard to a potential contribution of extracted compounds from the rubber stoppers to protein aggregation under worst-case conditions. All rubber stoppers were confirmed to comply with Ph. Eur. quality requirements. Extraction with 2-propanol under reflux-conditions for 3 h led to closure-specific extraction profiles of the tested samples. One type of rubber stopper exhibited a considerably greater number and higher content of extractables...
June 9, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Laura Abaandou, Joseph Shiloach
Creating efficient cell lines is a priority for the biopharmaceutical industry, which produces biologicals for various uses. A recent approach to achieving this goal is the use of non-coding RNAs, microRNA (miRNA) and small interfering RNA (siRNA), to identify key genes that can potentially improve production or growth. The ornithine decarboxylase antizyme 1 ( OAZ1 ) gene, a negative regulator of polyamine biosynthesis, was identified in a genome-wide siRNA screen as a potential engineering target, because its knock down by siRNA increased recombinant protein expression from human embryonic kidney 293 (HEK293) cells by two-fold...
June 8, 2018: Medical Sciences: Open Access Journal
Wenli Pan, Binli Xue, Chulei Yang, Linlin Miao, Lingli Zhou, Queyue Chen, Qing Cai, Yi Liu, Dongchun Liu, Haibing He, Yu Zhang, Tian Yin, Xing Tang
Deglycosylation is the most important gastrointestinal metabolism which ginsenosides are split off from glycosyl moieties by the enzymes secreted from intestinal microflora, and two possible metabolic pathways of protopanaxdiol-type and protopanaxtriol-type ginsenosides have been concluded. The former is deglycosylated at C-3 and/or C-20, and transformed to protopanaxdiol (PPD). By comparison, the latter is deglycosylated at C-6 and/or C-20, and eventually transformed to protopanaxtriol (PPT) instead. The pharmacokinetic behavior of protopanaxdiol-type ginsenosides (PPD-type ginsenosides) and protopanaxtriol-type ginsenosides (PPT-type ginsenosides) is different, mainly in a faster absorption and elimination rate of PPD-type ginsenosides, but almost all of ginsenosides have a low oral bioavailability, which is relevant to the properties, the stability in the gastrointestinal tract, membrane permeability and the intestinal and hepatic first-pass effect of ginsenosides...
June 5, 2018: Fitoterapia
Vasiliki Paraskevopoulou, Franco H Falcone
Since the introduction of recombinant protein expression in the second half of the 1970s, the growth of the biopharmaceutical field has been rapid and protein therapeutics has come to the foreground. Biophysical and structural characterisation of recombinant proteins is the essential prerequisite for their successful development and commercialisation as therapeutics. Despite the challenges, including low protein solubility and inclusion body formation, prokaryotic host systems and particularly Escherichia coli , remain the system of choice for the initial attempt of production of previously unexpressed proteins...
May 23, 2018: Microorganisms
Ye Hou, Hang Su, Zhiying Luo, Mingying Li, Xiaonan Ma, Ningning Ma
Phosphorylation and hydroxylation are post translational modifications (PTMs) rarely observed or reported in biopharmaceuticals. While developing a stable CHO cell line and a fed-batch process to produce a biosimilar dulaglutide, a GLP1-Fc fusion protein, we identified both serine phosphorylation and lysine hydroxylation. While the innovator dulaglutide contains less than 2% phosphorylated and only approximately 6.5% hydroxylated GLP1-Fc molecules, the clones that we obtained in the platform fed-batch process had approximately 20% phosphorylated and 25% hydroxylated GLP1-Fc molecules...
June 7, 2018: Biotechnology Journal
Zuzana Koci, Tomáš Boráň, Petr Krupa, Sarka Kubinova
Advanced therapy medicinal products (ATMPs) represent a new generation of biopharmaceuticals that comprise gene therapy medicinal products (GTMPs), somatic cell therapy products (CTMPs), tissue engineered products (TEPs) and combined advanced therapy medicinal products (cATMPs). The joint effort of the academia-industry-regulatory triangle translated scientific progress into nine authorised ATMPs in the European Community. This notion holds promise for the whole field of ATMP therapies that have been increasingly evaluated in a number of clinical studies, also in the Czech Republic (CR)...
June 5, 2018: Human Gene Therapy. Clinical Development
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