Screening of API batches related to a blend uniformity issue
Dry powder inhalation (DPI) formulation are one of the most challenging process step to be performed where even small differences in mixing behaviour may induce big differences in aerosolisation properties.
In the present case apparently equally good manufacturing batches of an API behaved significantly different in the mixing processing step with sever issues for the production of DPIs as a consequence.
The traditional approach is to perform different types of analysis in order to potentially spot significant differences in properties. However, neither conventional analysis of crystallinity (XRPD) and particle size distribution (LALLS) nor special analyses on particle deaggregation properties revealed any differences between the batches representing good and bad blending behaviour.
The Adroit approach was here to take this one step further and besides investigations of the batches “as is” also investigate the batches response to further solvent mediated provocation and investigate the consequences.
From a combination of different techniques it could be concluded that the batches had small but detectable differences in their inherent crystal packing properties. It was initially possible to separate the provided batches into good and bad using the described “before/after” methodology. Eventually, the methodology was further developed yielding reliable outcome from a carefully evaluated single solid state analysis (DSC) on each batch resulting in an efficient batch screening tool.