Excipient quantitation and drug distribution during formulation optimization.

An oral granules formulation experienced high drug content and increased variability when the process was scaled up from lab scale to clinical manufacturing scale. It was suspected that mannitol, due to its smaller particle size and lower density, was preferentially lost during the top spray granulation process, thereby causing active enrichment in the remaining granules. In order to troubleshoot the problem, rapidly evaluate solutions, and further optimize the formulation, a simple and rapid analytical technique was required.