Influence of polymeric excipients on crystal hydrate formation kinetics in aqueous slurries

Crystalline anhydrous active pharmaceutical ingredients (APIs) can potentially transform to the hydrate form during manufacturing processes involving water. The ability to understand and manipulate these transformations is important to maintain control of the solid state form of the API. The influence of various polymeric excipients on the anhydrate to hydrate transformation of caffeine, carbamazepine, and sulfaguanidine was investigated in this study. The transformation of the APIs in aqueous slurries was monitored using in‐line Raman measurements and the resultant kinetic profiles provided insight into the inhibitory ability of the polymers investigated. The results showed that cross‐linked poly(acrylic acid) inhibited the caffeine transformation and hydroxypropyl methylcellulose inhibited the carbamazepine transformation. None of the polymers tested were able to inhibit the sulfaguanidine transformation although some polymers were able to reduce the rate of the transformation with poly(vinylpyrrolidone) showing the greatest effect. It was found that the inhibitory polymers were able to either reduce crystal growth rates and/or increase the induction time preceding the nucleation event. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5198-5211, 2008