The Degradation Chemistry of GSK2879552: Salt Selection and Microenvironmental pH Modulation to Stabilize a Cyclopropyl Amine.

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.