Profoundly Improved Plasticity and Tabletability of Griseofulvin by in Situ Solvation and Desolvation during Spherical Crystallization

Griseofulvin (GSF) is a high dose drug exhibiting poor flowability and tabletability, which makes formulating a high drug loading tablet challenging. In using spherical crystallization to improve flowability, the spherical agglomerates (SA) of GSF were found to have profoundly improved tabletability over the as-received GSF. An improved plasticity of GSF SA was observed despite its identical crystal structure and larger particle size when compared to the as-received GSF. Tracking solid forms during the process revealed the formation of a GSF solvate with dichloromethane, the bridging liquid for spherical agglomeration. With subsequent desolvation during drying, nanoporous GSF crystals were obtained, which could be plastically deformed more easily and exhibited much improved tabletability.