The use of Pepsin to address in vitro extraction issues of NCE from liquid filled capsules with cross-linked gelatin
Cross-linking is a known aging phenomenon of gelatin, typically observed during stability studies, which might prevent in vitro solubilization of gelatin capsule shells and consequently impact the extraction of API from the dosage form. Cross-linking of protein chains through covalent bonding is associated with several causes including reaction with agents such as aldehydes and ketones, oxidizing agents, sugars, heat, humidity and light. Cross-linking makes gelatin less soluble in aqueous media and in vitro capsule shell opening is consequently delayed.
A case study is presented where several different self-micro-emulsifying solutions (SMEDDS) were being developed to increase the bioavailability of a very poorly soluble NCE. Since a solid dosage form was required, gelatin capsules were selected for encapsulation of the SMEDDS liquid formulations. However all developed formulations included PEG-derived excipients, which were sensitive to oxidative degradation upon storage, thus potentially leading to gelatin crosslinking and impacting the in vitro release of API. The enzymatic hydrolysis approach was successfully introduced in the sample preparation for assay and impurity determination of capsules to digest gelatin and allow complete extraction of API from the dosage form.
Recently presented by our expert, Paola Bisol, in collaboration with Neurocrine Biosciences, at AAPS 2017, download your copy of this scientific poster today and discover more!