Effect of excipient properties, water activity, and water content on the disproportionation of a pharmaceutical salt

Publication date: 30 July 2018 Source:International Journal of Pharmaceutics, Volume 546, Issues 1–2 Author(s): Mitulkumar A. Patel, Suman Luthra, Sheri L. Shamblin, Kapildev K. Arora, Joseph F. Krzyzaniak, Lynne S. Taylor Excipients are crucial components of most pharmaceutical formulations. In the case of a solid oral dosage formulation containing the salt form of a weakly ionizable drug, excipient selection is critical, as some excipients are known to cause salt disproportionation (conversion of salt to the free form). Therefore, robust formulation design necessitates an in-depth understanding of the factors impacting salt disproportionation during processing or storage as this can negatively impact product quality and performance. To date, there is an incomplete understanding of key excipient properties influencing salt disproportionation. Specifically, the potential roles of amorphous excipient glass transition temperature and excipient hygroscopicity, if any, on salt disproportionation are still not well understood. Furthermore, the relationship between the compression and the extent of salt disproportionation is an unknown factor. Herein, by utilizing various grades of polyvinylpyrrolidone (PVP), its copolymer, copovidone (PVPVA), and magnesium stearate, a systematic investigation of disproportionation was performed using pioglitazone HCl as a model salt of a weak base. It was observed that there was a poor correlation between excipient hygroscopicity and the...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research