Development of a vaginal tablet formulation with specified release profile parameters

Introduction. In vitro equivalence dissolution test is one of the main tests in drug development. In vitro equivalence dissolution test models the bioavailability of the active substance under the conditions of its use, allowing to assess the bioequivalence of drugs. The article describes an approach in which the results of in vitro equivalence dissolution test are used as a basis for obtaining a drug that differs in pharmaceutical dosage form and composition from the referent drug.

Aim. To select a composition of vaginal tablets that would be equivalent to suppositories on a lipophilic base according to in vitro equivalence dissolution test.

Materials and methods. The objects of the study are vaginal tablets and suppositories on a lipophilic base containing natamycin. The study was conducted using dissolution tester (the "Basket" apparatus) and a UV spectrophotometer to calculate the amount of released natamycin.

Results and discussion. The authors proposed an approach in which the development of a new dosage form of natamycin (vaginal tablets) is based on the development of similar to lipophilic base vaginal suppositories registered in the EAEU release profiles. For carrying out in vitro equivalence dissolution test, the authors developed samples of vaginal tablet formulations. The composition was selected to obtain a set of results with different release profiles and select the most optimal one both in terms of profile equivalence with the reference drug and the technological effectiveness (ease of introduction into production and cost-effectiveness of drug production) of the resulting composition. The formulations were selected to provide a set of release profiles that could be further compared with the reference. The objects of study were analyzed using a «Dissolution» test («Basket» apparatus), the released natamycin was monitored by UV spectrophotometry.

Conclusion. In vitro equivalence dissolution test was carried out for vaginal tablets containing natamycin, and the most promising formulation that meets the stated requirements for equivalence of release profiles was selected.

1. Demina N. B. Biopharmaceutical classification system as a tool for the development of drug formulations and their designs. Drug development & registration. 2017;(2):56–60. (In Russ.)

2. Kroustali V., Kanioura L., Resoulai E., Siopi M., Antonopoulou S., Meletiadis J. Antifungal susceptibility testing and determination of local epidemiological cut-off values for Candida species isolated from women with vulvovaginal candidiasis. Microbiology Spectrum. 2025;13(3):e0248824. DOI: 10.1128/spectrum.02488-24.

3. Ongarbayeva N. S., Balgimbaeva A. S., Baimakhanova B. B., Sadanov A. K., Lakhk O. N., Orazymbet S. E., Trenozhnikova L. P., Berezin V. E., Bogoyavlenskiy A. P., Miralimova Sh. M. Pharmacotherapy for vulvovaginal candidiasis. Microbiology and virology. 2024;2(45):83–107. DOI: 10.53729/MV-AS.2024.02.06.

4. Druzhininskaya O. V., Smekhova I. E. Dissolution media used in development and quality control of drugs. Drug development & registration. 2017;3:144–150. (In Russ.)

5. Meleshko A. V., Volkova A. M., Tyukova V. S., Panov A. V., Kedik S. A. Development of the «Dissolution» test method for vaginal suppositories Pimafucin®. Drug development & registration. 2025;14(1):254–264. (In Russ.) DOI: 10.33380/2305-2066-2025-14-1-1778.

6. Meleshko A. V. Determination of natamycin biopharmaceutical solubility. In: Horizons of biopharmaceuticals. Collection of scientific papers based on the materials of the IX International scientific and practical youth conference dedicated to the 89 th anniversary of Kursk State Medical University. May 23, 2024. Kursk: Publishing house JSC "Universitetskaya kniga"; 2024. P. 271–273. (In Russ.)

7. Sheskey P. J., Hancock B. C., Moss G. P., Goldfarb D. J., editors. Handbook of pharmaceutical excipients – Ninth edition. New York: Pharmaceutical Press; 2020. 1400 p.

8. Shohin I. E., Bagaeva N. S., Malashenko E. A., Kuzina V. N. Method of Estimating the Equivalence of Dissolution Profiles: a Modern View. Drug development & registration. 2020;9(2):145–150. (In Russ.) DOI: 10.33380/2305-2066-2020-9-2-145-150.

9. Zyryanov S. K., Butranova O. I., Ramenskaya G. V., Gildeeva G. N., Shohin I. E. In vitro equivalence evaluation of betahistine generic medicinal products as a tool potentially determining the efficacy of pharmacotherapy. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(11):43–48. DOI: 10.17116/jnevro201811811143.