Spherical Crystallization of Mebendazole to Improve Processability

Abstract

Spherical crystallization technique combines crystallization and agglomeration directly to generate spherical crystals with improved micromeretic properties, thus obviating need for further processing by granulation and agglomeration. The present study was focused on spherical crystallization of an antihelmentic drug - Mebendazole (MBZ) - using spherical agglomeration technique. Apart from being poorly water-soluble, MBZ exhibits poor flow and compressibility owing to its needle shaped crystal habit and electrostatic charge. Spherical agglomeration was carried out in the presence of different bridging liquids (hexane, octanol, toluene, dichloromethane) and polymers (polyethylene glycol, cross-povidone, starch, cross carmellose sodium, hydroxyl propyl methyl cellulose (HPMC), hydroxyl propyl cellulose (HPC), ethyl cellulose (EC), Eudragit S100, Eudragit RLPO, Eudragit RD100, Eudragit E), by employing different crystallization conditions such as variation of polymer type, polymer concentration, and rate of stirring. The final parameters were optimized to obtain crystals with an aspect ratio in the range of 1-2 compared to a value of 12 for untreated MBZ. These agglomerates retained form C of MBZ, and exhibited good flow properties, high bulk density and improved compressibility. Lower elastic:plastic energy (EE/PE) ratio for spherical crystals generated in the presence of Eudragit-S100 and Hydroxypropylcellulose (HPC) indicated better compressibilty of spherical crystals.