Development and Evaluation of Clotrimazole Solid Dispersion Using a Melting Method

Clotrimazole (CTMZ) is a vaginitis treatment drug, and its commercial product is Canesten®Vaginal Tablet, which are large tablets weighing approximately 1500 mg. It is a poorly soluble drug (biopharmaceutical classification system [BCS] Class II), and is a pH-dependent drug that dissolves well in low pH ranges but decreases in solubility as pH increases. The purpose of this study is to develop a CTMZ-solid dispersion (SD) with improved solubility and stability through screening using a melting method. The optimal formulation, SB-SD1 (CTMZ : Aerosil®300 : TPGS : K30®=1 : 2.5 : 5 : 1,w/w), had a dissolution rate of 99.2±0.1% (in pH 1.2 medium)/97.1±1.8% (in pH 4.5 buffer)/53.4±3.0% (in pH 6.8 buffer), which clearly demonstrated successful solubilization compared to Canesten®Vaginal Tablet, which had a dissolution rate of 99.8±0.5% (in pH 1.2 medium)/18.5±5.4% (in pH 4.5 buffer)/not detected (in pH 6.8 buffer). The SB-SD1 formulation also showed improved results in in vitro drug release test and pH-dependent solubility test. Physicochemical evaluation of the SB-SD1 formulation revealed thermal, chemical interaction, and crystalline intensity, and final formulations manufactured by different methods remained stable for six months. The successful solubilization and stabilization of CTMZ is expected to yield positive results in future efficacy evaluations.