Analytical Sciences and Development, GlaxoSmithKline, Upper Providence, Pennsylvania 19426.
Product and Process Engineering, GlaxoSmithKline, Stevenage, Hertfordshire, UK.
J Pharm Sci. 2019 Sep;108(9):2858-2864. doi: 10.1016/j.xphs.2019.04.026. Epub 2019 May 2.
The cyclopropyl amine moiety in GSK2879552 (1) degrades hydrolytically in high pH conditions. This degradation pathway was observed during long-term stability studies and impacted the shelf life of the drug product. This article describes the work to identify the degradation impurities, elucidate the degradation mechanism, and design a stable drug product. It was found that salt selection and control of the microenvironmental pH of the drug product formulation blend significantly improved the chemical stability of the molecule in the solid state.
GSK2879552（1）中的环丙胺部分在高 pH 条件下会发生水解降解。该降解途径在长期稳定性研究中被观察到，影响了药物产品的货架期。本文描述了鉴定降解杂质、阐明降解机制和设计稳定药物产品的工作。研究发现，盐的选择和控制药物产品制剂混合物的微环境 pH 值显著提高了分子在固态下的化学稳定性。
