Formulation and Evaluation of Fixed Dose Combination Tablets of Antifungal Drugs for Candida albicans Resistant to Fluconazole

  • Bhumika Thakur Shiva Institute of B.Pharmacy, Bilaspur, Himachal Pradesh, India-174004
  • Shiv Kumar Kushawaha Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101
  • Vinay Pandit Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101
  • Mahendra Singh Ashawat Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101
  • Pravin Kumar 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

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Author Biographies

Bhumika Thakur, Shiva Institute of B.Pharmacy, Bilaspur, Himachal Pradesh, India-174004

Shiva Institute of B.Pharmacy, Bilaspur, Himachal Pradesh, India-174004

Shiv Kumar Kushawaha, Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101

Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101

Vinay Pandit, Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101

Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101

Mahendra Singh Ashawat, Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101

Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101

Pravin Kumar, Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101

Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India-177101

References

1. Martin VM. The use of fluconazole and itracinazole in the treatment of candida albicans infection: a review. Journal of Antimicrobial Chemotherapy. 1999; 44(4):429-437.
2. Shield BE, Rosenbach M, Brown-Joel Z, Berger AP, FordBA and Wanat KA. Angioinvasive fungal infections impacting the skin. Journal of the American Academy of Dermatology. 2019 1993; 869-880.
3. Barchiesi F, Morbiducci V, Ancarani F, Scalise G. Emergence of oropharyngeal candidiasis caused by non-albicans species of Candida in HIV-infected patients. European Journal of Epidemiology. 1993; 9(4):455-456.
4. Powderly WG, Robinson K, Keath EJ. Molecular epidemiology of recurrent oral candidiasis in human immunodeficiency virus-positive patients: evidence for two patterns of recurrence. The Journal of Infectious Diseases. 1993; 168(2):463-466.
5. Barchiesi F, Hollis R J, McGough DA, Scalise G, Rinaldi MG, Pfaller MG. DNA subtypes and fluconazole susceptibilities of Candida albicans isolates from the oral cavities of patients with AIDS. Clincal Infectious Diseases. 1995: 20(3):634-640.
6. Barchiesi F, Najvar LK, Luther MF, Scalise G, Rinaldi MG, Graybill JR. Variation in fluconazole efficacy for Candida albicans strains sequentially isolated from oral cavities of patients with AIDS in an experimental murine candidiasis model. Antimicrobial Agents and Chemotherapy. 1996; 40(5):1317-1320.
7. Ghonnoum AM, Elewski B. Successful treatment of fluconazole-resistant oropharyngeal candidiasis by a combination of fluconazole and terbinafine. Clinical and Diagnostic Laboratory Immunology. 1999; 6(6):6921-6923.
8. Barchiesi F, Di Francesco LF, Scalise G. In vitro activities of terbinafine in combination with fluconazole and itraconazole against isolates of Candida albicans with reduced susceptibility to Azoles. Antimicrobial Agents and Chemotherapy. 1997; 41(8):1812-1814.
9. Ugurlin T, Ozaydin T. An overview on fixed dose combinations. Asian Journal of Pharmceutical Technology and Innovation. 2014; 2(4):75-81.
10. Pandey G, Mishra B. A new analytical Q-absorbance ratio method-Development and validation for simultaneous estimation method for lamivudine and isoniazid. ISRN spectroscopy. 2013; 1:1-5.
11. Validation of analytical procedures: Text and methodology Q2 (R1). ICH Harmonised Tripartite Guideline. 2005: 1-13.
12. Venkatachalam T, Lalitha KG. Spectrophotometric methods for simultaneous estimation of melatonin and Zolpidem from the combined tablet dosage form. Pharmacophore. 2014; 5(2):252-257.
13. Martin A, Swarbrick J, Cammarata, A. Physical pharmacy. 3rd ed. Mumbai: Varghese publishing house; 1991. P. 492-520.
14. United State Pharmacopoeia. 24th Asain ed. Tata Donnelly Limited, 2000.
15. Pavia DL, Lampman GM, Kriz GS, Vyvyan JR. Spectros-copy. 9th ed. Cengage Learning New Delhi, 2011.
16. Well J. Pharmaceutical preformulation. In: The science of dosage form design, Aulton ME, Ed; Toronto: Churchill Livingstone, 2003: 2nd ed, P. 113-138.
17. Lachman L, Lieberman HA, Kanig JL. Ed; Mumbai: Varghese publishing house; 1991. P. 293-345.
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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. JDDT [Internet]. 15Mar.2020 [cited 9Apr.2020];10(2):26-. Available from: http://jddtonline.info/index.php/jddt/article/view/3905