Apalutamide
(APA), a second-generation nonsteroidal antiandrogen
BCS Class II drug with poor solubility and high permeability. A novel
1:1 cocrystal of Apalutamide (APA) with methylparaben (MP) was identified
by cooling crystallization during the cocrystal screening and characterized
by various solid-state techniques, such as PXRD, DSC, TGA, FT-IR,
and 13C solid-state CP-MAS NMR spectroscopy. The crystal
structures of APA and its cocrystal (APA-MP) were determined by the
SC-XRD technique. The crystal structure analysis of the APA-MP cocrystal
revealed that the APA and MP molecules are connected through strong
O–H···O hydrogen bonds. The novel cocrystal
improves the solubility and dissolution rate in different physiological
conditions compared to poorly soluble APA due to strong hydrogen bond
between the drug and the coformer. The cocrystal is stable (physically
and chemically) under stress conditions, such as exposure to the relative
humidity, mechanical grinding, open exposure to atmosphere at cRT
(critical room temperature) and compression pressure of 10 tons. In
addition, the compatibility of the cocrystal with excipients used
in the drug product of APA (ERLEADA) was also investigated, and no
disproportionation of cocrystal was observed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.