Selective acceleration and inhibition of crystal growth of glass carbamazepine by low-concentration poly(ethylene oxide):effects of drug polymorph.

Abstract

Drug polymorphism attracts considerable interest within the pharmaceutical field. Herein, we investigate the impact of low-concentration poly(ethylene oxide) (PEO) on the crystal growth of carbamazepine (CBZ) polymorphs in the glassy state. The addition of 3%(w/w) PEO increases 5.3-fold the bulk crystal growth rates of CBZ form III and 36.7-fold of form IV at 40°C (T_g -11°C). However, the same content of PEO exhibits a negligible effect on the bulk crystal growth of form I. In addition, the effects of PEO on the crystal growth of the CBZ polymorph at the free surface are also explored. In the presence of 3%(w/w) PEO, surface growth rates of forms III and IV of CBZ are accelerated by 4.7-fold and 3.1-fold, respectively. For comparison, the same content of PEO exhibits an unexpected inhibitory effect on the surface growth rates of form I. Molecular-dynamic simulations attribute these polymorph-dependent effects of PEO mainly to the polymer enrichment at the interface and different crystal surface polymer interactions. This study is relevant for understanding the crystallization of amorphous pharmaceutical solids containing polymorphic drugs.