Formulation and Evaluation of Fixed Dose Combination Tablets of Antifungal Drugs for Candida albicans Resistant to Fluconazole
Background: The emergence of Candida albicans strains resistant to fluconazole (FLZ) had raised interest on combining other antifungals with FLZ. In vitro and clinical studies had indicated synergistic interaction between terbinafine and FLZ against strains resistant to FLZ and improved therapeutic efficacy. Objective: Formulation and evaluation of fixed dose combination (FDC) tablets of terbinafine HCl (TH) and FLZ for avoidance of resistance and improved therapeutic efficacy against C. albicans infections. Method: The compatibility of TH and FLZ together and with excipients was determined by FTIR spectroscopy. A UV-visible spectroscopic Q-absorbance ratio method was developed and validated for linearity, accuracy, precision, LOD and LOQ for simultaneous estimation of TH and FLZ. The FDC tablets was prepared by wet granulation using hydroxy propyl cellulose (1%, 2%, 3%, 4% and 5%) as binder and evaluated for pre-compression and post-compression parameters. Result and Discussion: The TH and FLZ were compatible together and with excipients used in FDC. The linearity range was found to be 0.5-3.0 µg/ml and 80-400 µg/ml for TH and FLZ, respectively. Percent RSD was less than 2% indicating good accuracy and precision for proposed method. The hardness and disintegration time of tablets increased and friability decreased with increased binder concentration. Formulation F2 and F3 showed more than 80% drug release within 30 minutes. Conclusion: The TH and FLZ were compatible and can be formulated as a FDC tablet. The UV-Visible spectrophotometric method developed for simultaneous estimation was simple, accurate and sensitive.
Keywords: Terbinafine, Fluconazole, Q-absorbance, Fixed Dose Combination, Candida albicans
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