Abstract

STUDIES ON FORMULATION AND EVALUATION OF CLOTRIMAZOLE COCRYSTALS

*Harita Desai, Archana Rajadhyax, Sakshi Jaiswal and Nayan Gulhane

ABSTRACT

Cocrystallization uses the approach of hydrogen bonding between a drug and a GRAS coformer to form a multicomponent crystalline compound with different physicochemical properties. Clotrimazole is a broad-spectrum antifungal drug belonging to BCS class II. It exhibits poor stability and solubility issues. Clotrimazole cocrystals were formulated by three techniques like Solvent evaporation, Ultrasonication and Antisolvent cocrystallization using different coformers scrutinized by COSMOquick software. The cocrystals were evaluated for visual morphology, drug content, infrared spectroscopy, Differential scanning calorimetry, X-ray diffraction studies, Scanning electron microscopy and saturation solubility studies. Fumaric acid was found to be the most optimized coformer. Solvent evaporation and Ultrasonication technique was found to be successful in yielding solid cocrystalline compound in stoichiometric ratio of 1:1 and 1:2. The obtained cocrystals were found to exhibit distinct visual morphology as compared to drug and coformer. The Fourier Transform Infrared spectroscopy studies were found to exhibit changes in spectral bands thus confirming hydrogen bond formation between Clotrimazole and coformer Fumaric acid. The interaction between the drug and coformer and the changes in crystallinity in the cocrystal was confirmed by Differential scanning calorimetry studies. Creation of new crystalline phase was confirmed by presence of new peaks at different 2 theta values for cocrystals by solvent evaporation and ultrasonication for coformer Fumaric acid in ratio of 1:1 and 1:2. Cocrystals of Clotrimazole with Fumaric acid by Solvent evaporation and ultrasonication in ratio of 1:1 were found to exhibit enhanced solubility in distilled water as compared to pure drug alone.

Keywords: Cocrystals, Clotrimazole, coformer, COSMOquick, ultrasonication, solvent evaporation.