Study of the effect of bifonazole concentration on the antifungal activity of vaginal suppositories

Authors

DOI:

https://doi.org/10.14739/2409-2932.2024.1.294647

Keywords:

bifonazole, soft drugs, antifungal agents, mathematical planning of the experiment

Abstract

The analysis of the current state of pharmacotherapy for vulvovaginal candidiasis reveals that there is a contemporary need for the development of soft dosage forms for the local treatment of infectious diseases affecting the vulva and vagina. This should be based on azole derivatives that, despite possessing a well-established wide spectrum of antifungal and antibacterial effects, have not been utilized for vaginal administration in domestic formulations. The successful realization of this project would enable the field of domestic dermatology to provide effective, compliant, and affordable drugs for gynecological practice to the general population of Ukraine. Additionally, it would establish a viable alternative to imported pharmacotherapeutic agents.

Aim. The purpose of this work is the scientific substantiation of the concentration of bifonazole in suppository compositions for vaginal use.

Materials and methods. Research was conducted to investigate the influence of bifonazole concentration ranging from 1 % to 15 % in soft dosage forms for vaginal use. Model compositions were formulated on a polyethylene oxide carrier, considering its solubility. The antifungal activity of the experimental suppository compositions was chosen as the optimization parameter and assessed using the diffusion method in agar against Candida albicans ATCC 885-653. Variance analysis of the results revealed a significant impact of bifonazole concentration on the antimycotic activity of the suppository compositions based on the model polyethylene oxide.

Results. The research results show that increasing the concentration of the active pharmaceutical ingredient in suppository masses above 10 % does not lead to a statistically significant increase in their antimycotic activity.

Conclusions. As a result of the conducted study on the antifungal effect of suppository masses with bifonazole on a model polyethylene oxide basis, it was found that the concentration of the active pharmaceutical ingredient has a statistically significant effect on the effectiveness of the soft dosage form. It was established that a ten percent concentration of bifonazole, equivalent to 0.3 g of the biologically active substance in vaginal suppositories, provides the optimal level of their antifungal effect.

Author Biographies

T. V. Mielnyk, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD-student of the Department of Medicines Technology

N. L. Kolycheva, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, Associate Professor of the Department of Microbiology, Virology and Immunology

References

Fakhim H, Vaezi A, Javidnia J, Nasri E, Mahdi D, Diba K, et al. Candida africana vulvovaginitis: Prevalence and geographical distribution. J Mycol Med. 2020;30(3):100966. doi: https://doi.org/10.1016/j.mycmed.2020.100966

Yano J, Sobel JD, Nyirjesy P, Sobel R, Williams VL, Yu Q, et al. Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes. BMC Womens Health. 2019;19(1):48. doi: https://doi.org/10.1186/s12905-019-0748-8

Bitew A, Abebaw Y. Vulvovaginal candidiasis: species distribution of Candida and their antifungal susceptibility pattern. BMC Womens Health. 2018;18(1):94. doi: https://doi.org/10.1186/s12905-018-0607-z

de Cássia Orlandi Sardi J, Silva DR, Anibal PC, de Campos Baldin JJ, Ramalho SR, Rosalen PL, et al. Vulvovaginal candidiasis: Epidemiology and risk factors, pathogenesis, resistance, and new therapeutic options. Curr Fungal Infect Rep. 2021;15(1):32-40. doi: http://dx.doi.org/10.1007/s12281-021-00415-9

Karrer S. Diseases of the female genitalia. In: Braun-Falco´s Dermatology. Berlin, Heidelberg: Springer Berlin Heidelberg; 2021. p. 1-19. Available from: https://doi.org/10.1007/978-3-662-58713-3_78-1

Lírio J, Giraldo PC, Amaral RL, Sarmento AC, Costa AP, Gonçalves AK. Antifungal (oral and vaginal) therapy for recurrent vulvovaginal candidiasis: a systematic review protocol. BMJ Open. 2019;9(5):e027489. doi: https://doi.org/10.1136/bmjopen-2018-027489

Ré ACS, Martins JF, Cunha-Filho M, Gelfuso GM, Aires CP, Gratieri T. New perspectives on the topical management of recurrent candidiasis. Drug Deliv Transl Res. 2021;11(4):1568-85. doi: https://doi.org/10.1007/s13346-021-00901-0

Shukla PK, Singh P, Yadav RK, Pandey S, Bhunia SS. Past, present, and future of antifungal drug development. In: Topics in Medicinal Chemistry. Cham: Springer International Publishing; 2016. p. 125-67. Available from: https://doi.org/10.1007/7355_2016_4

Hay RJ. Antifungal drugs. In: European Handbook of Dermatological Treatments. Berlin, Heidelberg: Springer Berlin Heidelberg; 2003. p. 700-10. Available from: https://doi.org/10.1007/978-3-662-07131-1_122

Shafiei M, Peyton L, Hashemzadeh M, Foroumadi A. History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action. Bioorg Chem. 2020;104:104240. doi: https://doi.org/10.1016/j.bioorg.2020.104240

Lewis RE, Wiederhold NP. Systemic Antifungal Agents. In: Diagnosis and Treatment of Fungal Infections. Cham: Springer International Publishing; 2023. p. 125-47. Available from: https://doi.org/10.1007/978-3-031-35803-6_8

Liu Y, Li M, Yi H, Song D, Lou Y, Fan S, et al. Efficacy and safety of Fufang Furong Effervescent Suppository for the treatment of mixed vaginitis: a randomized, multicenter, and non-inferiority study. Pharmacological Research - Modern Chinese Medicine. 2023 June; 7: Available from: https://www.sciencedirect.com/science/article/pii/S2667142523000118

Sobel JD, Sobel R. Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species. Expert Opin Pharmacother. 2018;19(9):971-7. doi: https://doi.org/10.1080/14656566.2018.1476490

Eldesouky HE, Mayhoub A, Hazbun TR, Seleem MN. Reversal of Azole Resistance in Candida albicans by Sulfa Antibacterial Drugs. Antimicrob Agents Chemother. 2018;62(3):e00701-17. doi: https://doi.org/10.1128/AAC.00701-17

Assress HA, Selvarajan R, Nyoni H, Mamba BB, Msagati TA. Antifungal azoles and azole resistance in the environment: current status and future perspectives - a review. Rev Environ Sci Biotechnol. 2021;20(4):1011-41. doi: http://dx.doi.org/10.1007/s11157-021-09594-w

Krishna AV, Gowda VD, Karki R. Formulation and Evaluation of Nanosponges Loaded Bifonazole for Fungal Infection. Anti-Infective Agents. 2020;19(1):64-75. doi: https://doi.org/10.2174/2211352518999200711164437

Kumar A, Kumar S. Intra vaginal drug delivery system (novel drug delivery system). Int J Res Appl Sci Biotechnol. 2020;7(6):234-41. doi: http://dx.doi.org/10.31033/ijrasb.7.6.33

Kobal IM, Hladyshev VV. Vyvchennia farmakotekhnolohichnykh kharakterystyk bifonazolu [Study of pharmacotechnological characteristics of bifonazole]. In: Naukovo-tekhnichnyi prohres i optymizatsiia tekhnolo-hichnykh protsesiv stvorennia likarskykh preparativ. Proceedings of the 6th scientific-practical conference Ternopil: TDMU "Ukrmedknyha"; 2016. p. 115-6. Ukrainian. Available from: http://dspace.zsmu.edu.ua/handle/123456789/4994

Hroshovyi TA, Martseniuk VP, Kucherenko LI, Vronska LP. Matematychne planuvannia eksperymentu pry provedenni naukovykh doslidzhen v farmatsii [Mathematical planning of an experiment during scientific research in pharmacy]. Ternopil, Ukraine: TDMU; 2008.

Pashayan MM, Hovhannisyan HG. Development of bifunctional vaginal suppositories by joint use terconazole and probiotic for treatment and prophylaxis of vulvovaginal candidiasis. Drug Dev Ind Pharm. 2021;47(9):1424-31. doi: https://doi.org/10.1080/03639045.2021.2001485

Published

2024-02-23

How to Cite

1.
Mielnyk TV, Kolycheva NL. Study of the effect of bifonazole concentration on the antifungal activity of vaginal suppositories. Current issues in pharmacy and medicine: science and practice [Internet]. 2024Feb.23 [cited 2024Nov.2];17(1):48-51. Available from: http://pharmed.zsmu.edu.ua/article/view/294647