Screening of Polysorbate-80 Composition by High Resolution Mass Spectrometry with Rapid H/D Exchange.

Polysorbate (PS) is a widely used polymeric excipient in biotherapeutic formulations to stabilize and protect protein drugs. Commercial PS is a highly heterogeneous mixture of structurally related components. PS composition can impact the stabilizer performance of PS in formulated protein drugs.

Comparative Characterization of Crofelemer Samples Using Data Mining and Machine Learning Approaches With Analytical Stability Data Sets.

There is growing interest in generating physicochemical and biological analytical data sets to compare complex mixture drugs, for example, products from different manufacturers. In this work, we compare various crofelemer samples prepared from a single lot by filtration with varying molecular weight cutoffs combined with incubation for different times at different temperatures. The 2 preceding articles describe experimental data sets generated from analytical characterization of fractionated and degraded crofelemer samples.

The Botanical Drug Substance Crofelemer as a Model System for Comparative Characterization of Complex Mixture Drugs.

Crofelemer is a botanical polymeric proanthocyanidin that inhibits chloride channel activity and is used clinically for treating HIV-associated secretory diarrhea. Crofelemer lots may exhibit significant physicochemical variation due to the natural source of the raw material. A variety of physical, chemical, and biological assays were used to identify potential critical quality attributes (CQAs) of crofelemer, which may be useful in characterizing differently sourced and processed drug products.

Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for Comparative Characterization of Complex Mixture Drugs.

As the second of a 3-part series of articles in this issue concerning the development of a mathematical model for comparative characterization of complex mixture drugs using crofelemer (CF) as a model compound, this work focuses on the evaluation of the chemical stability profile of CF. CF is a biopolymer containing a mixture of proanthocyanidin oligomers which are primarily composed of gallocatechin with a small contribution from catechin. CF extracted from drug product was subjected to molecular weight-based fractionation and thiolysis.

Inhibition and conformational change of SERCA3b induced by Bcl-2.

An interaction of Bcl-2 with SERCA had been documented in vitro using the SERCA1a isoform isolated from rat skeletal muscle [Dremina, E. S., Sharov, V.