Read by QxMD icon Read

protein formulation,biopharmaceuticals

Tongkai Chen, Chuwen Li, Ye Li, Yi Xiang, Simon Ming Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism Chinese herbal medicine but with poor water solubility and challenges to be delivered to the brain. We formulated SA as nanocrystals (SA-NC), aiming to improve its solubility, pharmacokinetic profile and thus provide a potential therapeutic agent for the treatment of Parkinson's disease (PD). The rod-shaped SA-NC had a particle size of ~160 nm with 33.3% drug loading, and the nanocrystals exhibited a fast dissolution rate in vitro. The intact drug nanocrystals could be internalized into Madin-Darby canine kidney (MDCK) cells, which were followed by rapid intracellular release, and most of the drug was transported to the basolateral side in its soluble form...
October 14, 2016: Molecular Pharmaceutics
Xinsheng Tian, M Reza Nejadnik, Dorrit Baunsgaard, Anette Henriksen, Christian Rischel, Wim Jiskoot
Nanoparticle tracking analysis (NTA) has attracted great interest for application in the field of submicron particle characterization for biopharmaceuticals. It has the virtue of direct sample visualization and particle-by-particle tracking, but the complexity of method development has limited its routine applicability. We systematically evaluated data collection and processing parameters as well as sample handling methods using shake-stressed protein samples. The camera shutter and gain were identified as the key factors influencing NTA results...
November 2016: Journal of Pharmaceutical Sciences
Bin Deng, Cristina Lento, Derek J Wilson
Protein therapeutics have emerged as a major class of biopharmaceuticals over the past several decades, a trend that has motivated the advancement of bioanalytical technologies for protein therapeutic characterization. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful and sensitive technique that can probe the higher order structure of proteins and has been used in the assessment and development of monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs) and biosimilar antibodies. It has also been used to quantify protein-ligand, protein-receptor and other protein-protein interactions involved in signaling pathways...
October 12, 2016: Analytica Chimica Acta
Kelly Zhang, Xiaodong Liu
Mixed-mode chromatography (MMC) is a fast growing area in recent years, thanks to the new generation of mixed-mode stationary phases and better understanding of multimode interactions. MMC has superior applications in the separation of compounds that are not retained or not well resolved by typical reversed-phase LC methods, especially for polar and charged molecules. Due to the multiple retention modes that a single MMC column can offer, often MMC provides additional dimension to a separation method by adjusting the mobile phase conditions...
October 25, 2016: Journal of Pharmaceutical and Biomedical Analysis
Hideyo Inouye, Damian Houde, Deniz B Temel, Lee Makowski
Characterization of immunoglobulin solutions at high concentrations represents a significant challenge. A current trend in the biopharmaceutical industry is to manufacture highly concentrated drug products, which can be used to deliver high doses in small volumes, via subcutaneous injections. Studying a molecule's structure and properties in its final drug product formulation is ideal, but characterization is typically performed under dilute solution conditions with critical stabilizing buffer components removed because of interference effects, which can result in an incomplete understanding of the molecule's properties...
November 2016: Journal of Pharmaceutical Sciences
Lukas Brückl, Rainer Hahn, Mauro Sergi, Stefan Scheler
Particle formation by physical degradation during the compounding step of biopharmaceuticals is a common concern and found in vessels with bottom mounted stirrers. It was potentially linked to sliding bearings, however, the exact mechanism was still unclear. In this study, custom designed small scale bearings in combination with an IgG1 antibody as model protein were used for investigations of the degradation mechanism inside a bearing. Thereby, abrasion of adsorbed proteins by contact sliding was identified as prevailing protein degradation mechanism and was quantified by an increase in turbidity and by monomer loss...
September 25, 2016: International Journal of Pharmaceutics
Fernanda Andrade, Pedro Fonte, Ana Costa, Cassilda Cunha Reis, Rute Nunes, Andreia Almeida, Domingos Ferreira, Mireia Oliva, Bruno Sarmento
AIM: Explore the use of polymeric micelles in the development of powders intended for pulmonary delivery of biopharmaceuticals, using insulin as a model protein. MATERIALS & METHODS: Formulations were assessed in vitro for aerosolization properties and in vivo for efficacy and safety using a streptozotocin-induced diabetic rat model. RESULTS: Powders presented good aerosolization properties like fine particle fraction superior to 40% and a mass median aerodynamic diameter inferior of 6 μm...
September 2016: Nanomedicine
M M R Meor Mohd Affandi, Minaketan Tripathy, A B A Majeed
Categorized as a Biopharmaceutics Classification System Class II drugs, atorvastatin (ATV) exhibits low aqueous solubility and bioavailability thus presenting an obstacle and great challenge to formulation researchers. Numerous studies are available in regard to the solubility enhancement of ATV, but very few actually describe this phenomenon in terms of thermodynamics and the solute-solvent interaction. Arginine (ARG) is an amino acid that has been reported to enhance the solubility of the highly insoluble wheat protein gluten through hydrogen bonding and π electron-cation interaction...
July 2016: Journal of Advanced Pharmaceutical Technology & Research
Katharina Christin Bauer, Mathias Göbel, Marie-Luise Schwab, Marie-Therese Schermeyer, Jürgen Hubbuch
The colloidal stability of a protein solution during downstream processing, formulation, and storage is a key issue for the biopharmaceutical production process. Thus, knowledge about colloidal solution characteristics, such as the tendency to form aggregates or high viscosity, at various processing conditions is of interest. This work correlates changes in the apparent diffusion coefficient as a parameter of protein interactions with observed protein aggregation and dynamic viscosity of the respective protein samples...
September 10, 2016: International Journal of Pharmaceutics
Mie Kristensen, Hanne Mørck Nielsen
Non-injectable delivery of peptide and protein drugs is hampered by their labile nature, hydrophilicity, and large molecular size; thus limiting their permeation across mucosae, which represent major biochemical and physical barriers to drugs administered via e.g. the oral, nasal, and pulmonary routes. However, in recent years cell-penetrating peptides (CPP) have emerged as promising tools to enhance mucosal delivery of co-administered or conjugated peptide and protein cargo and more advanced CPP-cargo formulations are emerging...
April 2016: Tissue Barriers
Lungile Nomcebo Thwala, Veronique Préat, Noémi Stefania Csaba
INTRODUCTION: Protein and peptide-based therapeutics are preferred therapeutics due to their specificity but are mainly administered by injection. Alternative routes for peptide delivery are preferred because of their ease of administration and increased patient compliance. AREAS COVERED: This review provides a critical overview of current strategies for non-invasive mucosal delivery routes of therapeutic proteins, with emphasis on their advantages and limitations...
June 28, 2016: Expert Opinion on Drug Delivery
Mohammad Amin Mohammad, Ian M Grimsey, Robert T Forbes
It is important for the formulators of biopharmaceuticals to predict the folding-unfolding transition of proteins. This enables them to process proteins under predetermined conditions, without denaturation. Depending on the apparent denaturation temperature (Tm) of lysozyme, we have derived an equation describing its folding-unfolding transition diagram. According to the water content and temperature, this diagram was divided into three different areas, namely, the area of the water-folded lysozyme phase, the area of the water-folded lysozyme phase and the bulk water phase, and the area of the denatured lysozyme phase...
July 21, 2016: Journal of Physical Chemistry. B
Kai Baumgartner, Steffen Großhans, Juliane Schütz, Susanna Suhm, Jürgen Hubbuch
In the biopharmaceutical industry it is mandatory to know and ensure the correct protein phase state as a critical quality attribute in every process step. Unwanted protein precipitation or crystallization can lead to column, pipe or filter blocking. In formulation, the formation of aggregates can even be lethal when injected into the patient. The typical methodology to illustrate protein phase states is the generation of protein phase diagrams. Commonly, protein phase behavior is shown in dependence of protein and precipitant concentration...
September 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
Kelly Zhang, Xiaodong Liu
Mixed-mode chromatography (MMC) is a fast growing area in recent years, thanks to the new generation of mixed-mode stationary phases and better understanding of multimode interactions. MMC has superior applications in the separation of compounds that are not retained or not well resolved by typical reversed-phase LC methods, especially for polar and charged molecules. Due to the multiple retention modes that a single MMC column can offer, often MMC provides additional dimension to a separation method by adjusting the mobile phase conditions...
September 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
Geetha Thiagarajan, Andrew Semple, Jose K James, Jason K Cheung, Mohammed Shameem
With the rapid growth of biopharmaceutical product development, knowledge of therapeutic protein stability has become increasingly important. We evaluated assays that measure solution-mediated interactions and key molecular characteristics of 9 formulated monoclonal antibody (mAb) therapeutics, to predict their stability behavior. Colloidal interactions, self-association propensity and conformational stability were measured using effective surface charge via zeta potential, diffusion interaction parameter (kD) and differential scanning calorimetry (DSC), respectively...
August 2016: MAbs
Serge Mathonet, Hanns-Christian Mahler, Stefan T Esswein, Maryam Mazaheri, Patricia W Cash, Klaus Wuchner, Georg Kallmeyer, Tapan K Das, Christof Finkler, Andrew Lennard
UNLABELLED: Regulatory monographs in Europe and the United States require drug products for parenteral administration to be "practically free" or "essentially free" of visible particles, respectively. Both terms have been used interchangeably and acknowledge the probabilistic nature of visual particle inspection. The probability of seeing a particle in a drug product container varies according to the size and nature of the particles as well as container and inspection conditions. Therefore, the term "without visible particles" can be highly misleading in the context of what is practically achievable...
July 2016: PDA Journal of Pharmaceutical Science and Technology
Brittany K Chavez, Cyrus D Agarabi, Erik K Read, Michael T Boyne, Mansoor A Khan, Kurt A Brorson
Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively...
2016: BioMed Research International
Jihye Lee, Bongchan Kim, Tae Hun Kim, Sun Hwa Lee, Hee Dong Park, Kyungha Chung, Sung-Hack Lee, Seungyup Paek, Eunice EunKyeong Kim, SukKyoon Yoon, Aeri Kim
LB30870, a new direct thrombin inhibitor, showed 80% reduction in oral bioavailability in fed state. The present study aims to propose trypsin binding as a mechanism for such negative food effect and demonstrate a prodrug approach to mitigate food effect. Effect of food composition on fed state oral bioavailability of LB30870 was studied in dogs. Various prodrugs were synthesized, and their solubility, permeability, and trypsin binding affinity were measured. LB30870 and prodrugs were subject to cocrystallization with trypsin, and the X-ray structures of cocrystals were determined...
April 4, 2016: Molecular Pharmaceutics
Christian Hildebrandt, Roman Mathaes, Rainer Saedler, Gerhard Winter
The crystalline state of proteins is deemed as a promising formulation platform for biopharmaceuticals. However, a stabilizing effect of protein crystal suspensions is controversially discussed. In fact, antibodies can display an increased aggregation and particle formation profile after the crystallization process compared with liquid or solid amorphous formulations. Nevertheless, studies regarding aggregate formation and its origin remain meager in literature. It was the aim of this study to investigate these aspects for a model IgG antibody (mAb1), which shows an increased aggregate formation after crystallization with polyethylene glycol...
March 2016: Journal of Pharmaceutical Sciences
David P Cowcher, Tanja Deckert-Gaudig, Victoria L Brewster, Lorna Ashton, Volker Deckert, Royston Goodacre
The correct glycosylation of biopharmaceutical glycoproteins and their formulations is essential for them to have the desired therapeutic effect on the patient. It has recently been shown that Raman spectroscopy can be used to quantify the proportion of glycosylated protein from mixtures of native and glycosylated forms of bovine pancreatic ribonuclease (RNase). Here we show the first steps toward not only the detection of glycosylation status but the characterization of glycans themselves from just a few protein molecules at a time using tip-enhanced Raman scattering (TERS)...
February 16, 2016: Analytical Chemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"