(178e) Crystallization of Active Pharmaceutical Ingredient in Drug Product: A Case Study

Age-related macular degeneration (AMD) is a leading cause of blindness and visual impairment in older adults (>50 years). It occurs in "dry" and "wet" forms. The majority of significant vision loss is caused by wet AMD, which is attributed to the abnormal blood vessel growth in the choriocapillaris of eyes. The current standard care is repeated injections of anti-VEGF agents in the eyes. GSK has been developing Pazopanib eye drop (a multi-targeted receptor tyrosine kinase inhibitor) as an alternative treatment for wet AMD. Formulations under development are highly supersaturated Captisol based GW786034 solution. This presentation will describe our approach taken to understand long term stability of the eye drop formulation (drug product) through GW786034 crystallization kinetics study, in which concentrations of GW786034 and Captsol, pH and temperature were examined and PAT was employed. Mechanism of GW786034 solid formation and impacts of supersaturation of the formulations on drug product manufacture and storage will also be discussed.