Physical stability of crystal hydrates and their anhydrates in the presence of excipients

摘要: Abstract There are few studies in the literature that deal with effect of excipients on kinetics vapor phase induced hydrate−anhydrate transformations. The main purpose this study was to probe stability systems presence hygroscopic and nonhygroscopic following exposure either dehydrating or hydrating conditions. Physical mixtures compacts model hydrate formers (theophylline carbamazepine) (mannitol, microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP) K12 K90) were stored at 22°C varying relative humidities. Raman spectroscopy used monitor transformation between anhydrate. In general, found have no promote dehydration. For formation, could accelerate, retard, influence hydration kinetics. MCC only minimal effects dehydration compounds, whereas mannitol enhanced but had little hydration. Different PVP grades showed a variety effects: PVPK12 greatly both theophylline monohydrate (MT) carbamazepine dihydrate (DC). PVPK90 also DC, negligible MT. retarding anhydrous (AT) transformation, conversion (AC) retarded AT, AC. Optical microscopy X-ray powder diffraction suggested (in particular K12), when high RH, able result partial dissolution active pharmaceutical ingredient hence changed process from solid state solution-mediated transformation. summary, is complex needs be rationalized terms several excipient properties including physical state, chemical composition, possibility specific API−excipient interactions. It concluded multitude factors will dictate, often complicate, final formers. © 2005 Wiley-Liss, Inc. American Pharmacists Association