Formulation Impact on Sustained
Release Pellet Matrix and Drug Release
Drug formulation is one of the key factors for generic drug developers in reproducing and improving upon the efficacy of the brand-name reference listed drug (RLD). For this study, we applied correlative imaging to study the microstructures of sustained release pellets in RLD and generic ibuprofen drug products. Dual energy X-ray tomography was used to reveal primary structures (sugar core, coating, and void space) and FIB-SEM to study secondary structures (API particles and microporosity matrix). Cross section imaging using FIB-SEM and a proprietary sample preparation protocol revealed microstructural differences of four generic samples, which are linked to an explanation of the differences in their release performance and failure to meet a pharmacopeia performance guidelines. In particular, differences in the tightness of the microporosity matrix was correlated with the release performance of the sustained release pellets. This study demonstrated that FIB-SEM cross sectioning and 3D imaging as important methodologies to study micro and nano-scale structural features resulting from different drug formulations and manufacturing conditions.
FIB-SEM reveals a rich microporosity network within a sustained release pellet.
PDF slides presenting the case study of the microstructure bioequivalence assessment of microporosity and dissolution performance of an Ibuprofen pellet in collaboration with GSK