Thakur et al Journal of Drug Delivery & Therapeutics. 2020; 10(2):26-36 ISSN: 2250-1177 [26] CODEN (USA): JDDTAO Available online on 15.03.2020 at http://jddtonline.info Journal of Drug Delivery and Therapeutics Open Access to Pharmaceutical and Medical Research © 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted non-commercial use, provided the original work is properly cited Open Access Research Article Formulation and Evaluation of Fixed Dose Combination Tablets of Antifungal Drugs for Candida albicans Resistant to Fluconazole Bhumika Thakur 1 *, Shiv Kumar Kushawaha 2 , Vinay Pandit 2 , Mahendra Singh Ashawat 2 , Pravin Kumar 2 1 Shiva Institute of B.Pharmacy, Bilaspur, Himachal Pradesh, India-174004 2 Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101 ABSTRACT 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 Article Info: Received 03 Jan 2020; Review Completed 10 Feb 2020; Accepted 18 Feb 2020; Available online 15 March 2020 Cite this article as: Thakur B, Kushawaha SK, Pandit V, Ashawat MS, Kumar P, Formulation and Evaluation of Fixed Dose Combination Tablets of Antifungal Drugs for Candida albicans Resistant to Fluconazole, Journal of Drug Delivery and Therapeutics. 2020; 10(2):26-36 http://dx.doi.org/10.22270/jddt.v10i2.3905 *Address for Correspondence: Bhumika Thakur, Shiva Institute of B.Pharmacy, Bilaspur, Himachal Pradesh, India-174004 1. INTRODUCTION Candida albicans is the most important fungal strain accountable for most of the localized and systemic fungal infections 1 . Systemic candidiasis is the leading cause of mycosis-associated mortality in the United States and is globally recognized as a cause of significant morbidity 2 . Immunocompromised patients, such as AIDS patients or are neutropenic due to cancer therapy, are at specific threat of evolving local C. albicans infections, which may become systemic 3, 4 . Fluconazole (FLZ) is an orally active triazole agent, well established as a first-line treatment for localized and systemic C. albicans infections 1 . In the past decades, advent of resistant C. albicans strains to FLZ on long term suppressive therapy has been reported in AIDS patient with oropharyngeal candidiasis 5, 6 . An attractive therapeutic option in these circumstances is combining other antifungals with the FLZ for synergistic effect and widened spectrum against FLZ resistant fungal strains. The use of terbinafine an orally and topically active antifungal has been recommended in combination with FLZ for the cases with FLZ resistant C. albicans 7 . Terbinafine is act as a fungicidal against a broad spectrum of fungi including dermatophytes, filamentous, dimorphic organisms and some yeast such as Candida parapsilosis 8 . Synergistic interactions of terbinafine with azoles and other compounds against Candida albicans have been reported by many investigators. Ghonnoum and Elewski 6 had reported the successful treatment of oropharyngeal candidiasis patients with a combination of FLZ and terbinafine who had also FLZ-refractory. In an in vitro study, Barchiesi and colleagues concluded a synergistic interaction between terbinafine and FLZ against C. albicans strain with reduced susceptibility to FLZ 7 . The above evidences suggested that combining the terbinafine and FLZ in fixed dose combinations (FDC) can be a better approach for the treatment of cases associated with FLZ resistant C. albicans. FDC are dosage forms which contain two or more active