European Journal of Biomedical and Pharmaceutical Sciences

CO-CRYSTALLIZATION FOR ENHANCED DISSOLUTION RATE OF FLUTAMIDE

Mohamed F. Zaky*, Ebtessam A. Essa, Ahmed A. Bosela and Gamal M. El Maghraby

ABSTRACT

Flutamide is an orally active anti-androgenic agent of non-steroidal origin which is approved for treatment of prostatic carcinoma. It has low and variable oral bioavailability. This is mainly attributed to its poor dissolution behavior. Co-crystallization of drugs with inert co-former is an emerging technique for enhancing dissolution rate. Accordingly, the objective of this work was to investigate the efficacy of sucralose as a potential co-crystal co-former for enhancing the dissolution rate of flutamide. Co-crystal formation involved acetone assisted co-grinding after mixing flutamide with increasing molar ratios of sucralose (1:1, 1:2 and 1:3). The prepared formulations were subjected to physical characterization in addition to monitoring the dissolution behavior. The characterization employed Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. These investigations provided evidence for co-crystal formation between the drug and sucralose. Co-crystals were formed with 1:2 drug to sucralose (molar ratio) being optimum for co-crystallization process. The dissolution studies revealed faster dissolution rate of the drug from co-crystals compared to the pure unprocessed drug or that which was subjected to wet grinding in absence of sucralose. The study also revealed dimorphic conversion of flutamide after precipitation from acetone. The study introduced sucralose as co-crystal co-former for enhanced dissolution of flutamide.

Keywords: Flutamide; co-crystallization; sucralose; dissolution rate.