Identification and quantitation of extractables from cellulose acetate butyrate (CAB) and estimation of their in vivo exposure levels

The purpose of this study was to qualitatively and quantitatively determine potential cellulose acetate butyrate (CAB) extractables in a way to meaningfully predict the in vivo exposure resulting from clinical administration. Extractions of CAB-381-20 were per-formed in several solvent systems, consistently resulting in the detection of three extractables. The extractables have been identified as acetic acid, butyric acid, and E-2-ethyl-2-hexenoic acid (E-EHA) by LC/UV, LC/MS and NMR. Extraction studies of CAB powders in acetonitrile/phosphate buffer demonstrated quantitative extraction in 1 h for acetic acid (similar to150 mug/g), butyric acid (similar to200 mug/g), and EHA (similar to20 mug/g). Subsequently, extraction studies for CAB powders and coated tablets in USP simulated gastric and intestinal fluids were performed to evaluate potential in vivo exposure. Similarly, acetic and butyric acids were quantitatively extracted from CAB-381-20 powder after 24 h exposure in both USP simulated fluids. The amounts of EHA extracted from CAB powder after 24 h were determined to be 2 and 16 mug/g in USP simulated gastric and intestinal fluids, respectively. After 24 h exposure in USP simulated fluids, the maximum amount of EHA extracted corresponds to <0.3 mug of EHA per tablet. Pepsin and pancreatin in USP Simulated fluids had no effect on EHA extraction and quantitation. (C) 2004 Elsevier B.V. All rights reserved.