Category: Formulation and Quality
Purpose: During the early stage formulation development, significant degradation of compound A (in the HPMCAS based SDD material under 40oC/75%RH storage condition) was observed. It was an unusual observation because the API is stable under solution and solid stability studies and HPMCAS is regarded as a relatively inert polymer. The degradant was identified as succinate ester of the API by LC-MS and 1HNMR after isolating the pure degradant fraction from the SDD degradation mixture using supercritical fluid chromatography (SFC). The degradant was formed when the hydroxyl group of the API interacted with the succinate group on HPMCAS polymer. The impact of this degradation upon long term storage needs to be assessed.
Methods: The degradation kinetics was studied at 40oC, 60oC and 75oC. The compound A SDD solid materials were stored at three temperatures and samples were analyzed by HPLC at timepoints shown in Table 1.
Table 1. Stability conditions and time points
T0, T-8day, T-16day and T-23day
T0, T-2day, T-4day and T-7day
T0, T-4hr, T-8hr, T-24hr, T-32hr and T-96hr
Hours needed for 0.15% degradation
Days needed for 0.15% degradation