Role of excipients on solid-state properties of piroxicam during processing

Abstract

There is a need for an improved process understanding of solid dosage pharmaceuticals. In the present study, Raman spectroscopy together with partial least squares (PLS) regression was used to monitor the solid-state composition of piroxicam during processing in the presence of excipients. It was found that including variable selection in PLS regression offers improved quantitative models in terms of predictive performance, easier interpretation of results and reduced experimental workload relative to full-spectrum PLS regression. By means of the applied interval PLS (iPLS) regression model, it was observed that excipients with high water-absorbing potential (microcrystalline cellulose and hydroxypropyl cellulose) and a water-activity-reducing solvent (ethanol) delayed the onset of monohydrate formation during processing in aqueous environments. An alkalizing excipient (sodium bicarbonate) decreased the onset time of monohydrate formation during wet granulation and decreased the dehydration rate during a drying operation. In this study it is demonstrated that the physical stability of hydrate-anhydrate systems in process environments is complicated by a multitude of factors on both macroscopic level and molecular level, and that variable selection for PLS regression is a valuable tool for screening the effects of excipients on the solid-state properties of pharmaceuticals.