Paclitaxel Crystal Seeds with Different Intrinsic Properties and Their Impact on Dissolution of Paclitaxel-HPMCAS Amorphous Solid Dispersions

Abstract

Dissolving a formulation containing the drug in amorphous form can lead to supersaturation and increase the free drug concentration relative to that achieved by dissolving the crystalline form. However, the amorphous form is thermodynamically metastable, and hence crystallization can occur both in the formulation and from the supersaturated drug solution generated upon dissolution. From a practical perspective, it may not be possible to always produce amorphous solid dispersions (ASDs) that are completely free of residual crystallinity. Crystals formed in different environments can have dissimilar intrinsic properties, which in turn can influence crystal growth kinetics and hence the dissolution profile of the ASD. Herein, paclitaxel, a compound that crystallizes as needles, was used as a model compound to explore the impact of crystal seeds on the (de)supersaturation profile obtained following dissolution of an amorphous solid dispersion. Crystal seeds generated under four different conditions had differ...