Light Obscuration Measurements of Highly Viscous Solutions: Sample Pressurization Overcomes Underestimation of Subvisible Particle Counts
Journal Title: The AAPS Journal - Year 2014, Vol 16, Issue 5
Abstract
Light obscuration (LO) is the current standard technique for subvisible particle analysis in the quality control of parenterally administered drugs, including therapeutic proteins. Some of those, however, exhibit high viscosities due to high protein concentrations, which can lead to false results by LO measurements. In this study, we show that elevated sample viscosities, from about 9 cP, lead to an underestimation of subvisible particle concentrations, which is easily overlooked when considering reported data alone. We evaluated a solution to this problem, which is the application of sample pressurization during analysis. The results show that this is an elegant way to restore the reliability of LO analysis of highly viscous products without the necessity of additional sample preparation.
Authors and Affiliations
Daniel Weinbuch, Wim Jiskoot, Andrea Hawe
In vitro–In Vivo Correlations: Tricks and Traps
In vitro–in vivo correlation (IVIVC) is a biopharmaceutical tool recommended to be used in development of formulation. When validated, it can speed up development of formulation, be used to fix dissolution limits...
Aerosolization of lipoplexes using AERx® pulmonary delivery system
The lung represents an attractive target for delivering gene therapy to achieve local and potentially systemic delivery of gene products. The objective of this study was to evaluate the feasibility of the AERx Pulmonary...
In Vivo Quantitative Prediction of the Effect of Gene Polymorphisms and Drug Interactions on Drug Exposure for CYP2C19 Substrates
The online version of this article (doi:10.1208/s12248-012-9431-9) contains supplementary material, which is available to authorized users.
Non-Arrhenius Protein Aggregation
Protein aggregation presents one of the key challenges in the development of protein biotherapeutics. It affects not only product quality but also potentially impacts safety, as protein aggregates have been shown to be l...
Development of a Preclinical PK/PD Model to Assess Antitumor Response of a Sequential Aflibercept and Doxorubicin-Dosing Strategy in Acute Myeloid Leukemia
Timing of the anti-angiogenic agent with respect to the chemotherapeutic agent may be crucial in determining the success of combination therapy in cancer. We investigated the effects of sequential therapy with the potent...