A systematic review of mucoadhesive vaginal tablet testing

Ismin Zainol Abidin; Emma Murphy; Gustavo Waltzer Fehrenbach; Emanuele Rezoagli; Noel Gately; Ian Major

doi:10.33393/dti.2023.2477

Authors

Ismin Zainol Abidin PRISM Research Institute, Technological University of the Shannon: Midlands Midwest, Athlone Campus, Westmeath - Ireland https://orcid.org/0000-0003-2912-4210
Emma Murphy PRISM Research Institute, Technological University of the Shannon: Midlands Midwest, Athlone Campus, Westmeath - Ireland and Shannon Applied Biotechnology Centre, Department of Applied Science, Faculty of Applied Sciences and Technology, Technological University of the Shannon: Midlands Midwest, Moylish Campus, Limerick - Ireland and LIFE—Health and Biosciences Research Institute, Technological University of the Shannon, Midwest Campus, Limerick - Ireland https://orcid.org/0000-0002-5620-0058
Gustavo Waltzer Fehrenbach Bioscience Research Institute, Technological University of the Shannon: Midlands Midwest, Athlone Campus, Westmeath - Ireland https://orcid.org/0000-0002-9389-3391
Emanuele Rezoagli Department of Emergency and Intensive Care, San Gerardo University Hospital, Monza - Italy and School of Medicine and Surgery, University of Milano-Bicocca, Monza - Italy https://orcid.org/0000-0002-4506-7212
Noel Gately PRISM Research Institute, Technological University of the Shannon: Midlands Midwest, Athlone Campus, Westmeath - Ireland https://orcid.org/0000-0002-2610-2975
Ian Major PRISM Research Institute, Technological University of the Shannon: Midlands Midwest, Athlone Campus, Westmeath - Ireland https://orcid.org/0000-0002-0538-9786

DOI:

https://doi.org/10.33393/dti.2023.2477

Keywords:

Dissolution, Mucoadhesion, Physicochemical, Swelling

Abstract

Drug administration through the vaginal tract is one of the oldest modalities of pharmacotherapy, and it is also one of the most explored. Since the vaginal cavity has a wide surface area, a plentiful blood supply, and a complex network of blood arteries, it can evade hepatic first-pass metabolism and obtain high local drug concentrations. Vaginal pills look to be a good dose form since they are simple to use, portable, and can easily deliver the required amount of medicine. Vaginal formulations, on the other hand, are vulnerable to rapid expulsion due to the vaginal tract’s self-cleaning action, which reduces the formulation’s efficiency. Currently, there is an increasing amount of focus on mucoadhesive vaginal formulation research and development to fix the formulation at the place where the medicine can be released and/or absorbed. This article examines all of the strategies used by researchers to develop a mucoadhesive vaginal tablet that is safe, effective, and comfortable for the user.

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References

das Neves J, Palmeira-de-Oliveira R, Palmeira-de-Oliveira A, Rodrigues F, Sarmento B. Vaginal mucosa and drug delivery. In: Khutoryanskiy VV, ed. Mucoadhesive materials and drug delivery systems. Chichester: John Wiley & Sons 2014; 99-132. https://doi.org/10.1002/9781118794203.ch05 DOI: https://doi.org/10.1002/9781118794203.ch05

das Neves J, Notario-Pérez F, Sarmento B. Women-specific routes of administration for drugs: a critical overview. Adv Drug Deliv Rev. 2021;176:113865. https://doi.org/10.1016/j.addr.2021.113865 PMID:34280514 DOI: https://doi.org/10.1016/j.addr.2021.113865

de Araújo Pereira RR, Bruschi ML. Vaginal mucoadhesive drug delivery systems. Drug Dev Ind Pharm. 2012;38(6):643-652. https://doi.org/10.3109/03639045.2011.623355 PMID:21999572 DOI: https://doi.org/10.3109/03639045.2011.623355

Acartürk F. Mucoadhesive vaginal drug delivery systems. Recent Pat Drug Deliv Formul. 2009;3(3):193-205. https://doi.org/10.2174/187221109789105658 PMID:19925443 DOI: https://doi.org/10.2174/187221109789105658

Bartkowiak A, Rojewska M, Hyla K, Zembrzuska J, Prochaska K. Surface and swelling properties of mucoadhesive blends and their ability to release fluconazole in a mucin environment. Colloids Surf B Biointerfaces. 2018;172:586-593. https://doi.org/10.1016/j.colsurfb.2018.09.014 PMID:30218984 DOI: https://doi.org/10.1016/j.colsurfb.2018.09.014

Vermani K, Garg S. The scope and potential of vaginal drug delivery. Pharm Sci Technol Today. 2000;3(10):359-364. https://doi.org/10.1016/S1461-5347(00)00296-0 PMID:11050460 DOI: https://doi.org/10.1016/S1461-5347(00)00296-0

Zhang L, De Salvo R, Ehret A, Young K, Trapp S. Vulvovaginal candidiasis: a real-world evidence study of the perceived benefits of Canesten®. SAGE Open Med. 2022;10:20503121221085437. https://doi.org/10.1177/20503121221085437 PMID:35371482 DOI: https://doi.org/10.1177/20503121221085437

McCoy CF, Spence P, Dallal Bashi YH, et al. Use of simulated vaginal and menstrual fluids to model in vivo discolouration of silicone elastomer vaginal rings. Int J Pharm X. 2021;3:100081. https://doi.org/10.1016/j.ijpx.2021.100081 PMID:34027386 DOI: https://doi.org/10.1016/j.ijpx.2021.100081

Chollet JA. Efficacy and safety of ultra-low-dose Vagifem (10 mcg). Patient Prefer Adherence. 2011;5:571-574. https://doi.org/10.2147/PPA.S22940 PMID:22163155 DOI: https://doi.org/10.2147/PPA.S22940

Machado RM, Palmeira-de-Oliveira A, Gaspar C, Martinez-de-Oliveira J, Palmeira-de-Oliveira R. Studies and methodologies on vaginal drug permeation. Adv Drug Deliv Rev. 2015;92:14-26. https://doi.org/10.1016/j.addr.2015.02.003 PMID:25689736 DOI: https://doi.org/10.1016/j.addr.2015.02.003

Pacheco-Quito E-M, Ruiz-Caro R, Rubio J, Tamayo A, Veiga MD. Carrageenan-based acyclovir mucoadhesive vaginal tablets for prevention of genital herpes. Mar Drugs. 2020;18(5):249. https://doi.org/10.3390/md18050249 PMID:32403219 DOI: https://doi.org/10.3390/md18050249

Hassan AS, Soliman GM, Ali MF, El-Mahdy MM, El-Gindy GEA. Mucoadhesive tablets for the vaginal delivery of progesterone: in vitro evaluation and pharmacokinetics/pharmacodynamics in female rabbits. Drug Dev Ind Pharm. 2018;44(2):224-232. https://doi.org/10.1080/03639045.2017.1386203 PMID:28956650 DOI: https://doi.org/10.1080/03639045.2017.1386203

Cevher E, Açma A, Sinani G, Aksu B, Zloh M, Mülazımoğlu L. Bioadhesive tablets containing cyclodextrin complex of itraconazole for the treatment of vaginal candidiasis. Int J Biol Macromol. 2014;69:124-136. https://doi.org/10.1016/j.ijbiomac.2014.05.033 PMID:24857873 DOI: https://doi.org/10.1016/j.ijbiomac.2014.05.033

Abu El-Enin ASM, Elbakry AM, El Hosary R, Fouad Lotfy MA, Yahia R. Formulation, development, in vivo pharmacokinetics and pharmacological efficacy evaluation of novel vaginal bioadhesive sustained core-in-cup salbutamol sulphate tablets for preterm labor. J Drug Deliv Sci Technol. 2020;60:102076. https://doi.org/10.1016/j.jddst.2020.102076 DOI: https://doi.org/10.1016/j.jddst.2020.102076

Garg S, Goldman D, Krumme M, Rohan LC, Smoot S, Friend DR. Advances in development, scale-up and manufacturing of microbicide gels, films, and tablets. Antiviral Res. 2010;88(suppl 1):S19-S29. https://doi.org/10.1016/j.antiviral.2010.09.010 PMID:21109064 DOI: https://doi.org/10.1016/j.antiviral.2010.09.010

Cazorla-Luna R, Notario-Pérez F, Martín-Illana A, et al. Chitosan-based mucoadhesive vaginal tablets for controlled release of the anti-HIV drug tenofovir. Pharmaceutics. 2019;11(1):20. https://doi.org/10.3390/pharmaceutics11010020 PMID:30621307 DOI: https://doi.org/10.3390/pharmaceutics11010020

Clark MR, Peet MM, Davis S, Doncel GF, Friend DR. Evaluation of rapidly disintegrating vaginal tablets of tenofovir, emtricitabine and their combination for HIV-1 prevention. Pharmaceutics. 2014;6(4):616-631. https://doi.org/10.3390/pharmaceutics6040616 PMID:25494201 DOI: https://doi.org/10.3390/pharmaceutics6040616

Abidin IZ, Rezoagli E, Simonassi-Paiva B, et al. A bilayer vaginal tablet for the localized delivery of disulfiram and 5-fluorouracil to the cervix. Pharmaceutics. 2020;12(12):1185. https://doi.org/10.3390/pharmaceutics12121185 PMID:33291349 DOI: https://doi.org/10.3390/pharmaceutics12121185

Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. Chichester: John Wiley & Sons; 2019. https://doi.org/10.1002/9781119536604 DOI: https://doi.org/10.1002/9781119536604

Lee C-H, Chien YW. Development and evaluation of a mucoadhesive drug delivery system for dual-controlled delivery of nonoxynol-9. J Control Release. 1996;39(1):93-103. https://doi.org/10.1016/0168-3659(95)00142-5 DOI: https://doi.org/10.1016/0168-3659(95)00142-5

Perrone M, Lopalco A, Lopedota A, et al. S-preactivated thiolated glycol chitosan useful to combine mucoadhesion and drug delivery. Eur J Pharm Biopharm. 2018;132:103-111. https://doi.org/10.1016/j.ejpb.2018.09.015 PMID:30253185 DOI: https://doi.org/10.1016/j.ejpb.2018.09.015

Rojewska M, Bartkowiak A, Milanowski B, Prochaska K, Lulek J. Physicochemical and release studies of new mucoadhesive fluconazole delivery systems. Colloids Surf A Physicochem Eng Asp. 2019;566:11-20. https://doi.org/10.1016/j.colsurfa.2018.12.058 DOI: https://doi.org/10.1016/j.colsurfa.2018.12.058

Szymańska E, Winnicka K, Amelian A, Cwalina U. Vaginal chitosan tablets with clotrimazole-design and evaluation of mucoadhesive properties using porcine vaginal mucosa, mucin and gelatine. Chem Pharm Bull (Tokyo). 2014;62(2):160-167. https://doi.org/10.1248/cpb.c13-00689 PMID:24492586 DOI: https://doi.org/10.1248/cpb.c13-00689

Cevher E, Sensoy D, Zloh M, Mülazimoğlu L. Preparation and characterisation of natamycin: γ-cyclodextrin inclusion complex and its evaluation in vaginal mucoadhesive formulations. J Pharm Sci. 2008;97(10):4319-4335. https://doi.org/10.1002/jps.21312 PMID:18288724 DOI: https://doi.org/10.1002/jps.21312

Gök MK, Demir K, Cevher E, et al. The effects of the thiolation with thioglycolic acid and l-cysteine on the mucoadhesion properties of the starch-graft-poly(acrylic acid). Carbohydr Polym. 2017;163:129-136. https://doi.org/10.1016/j.carbpol.2017.01.065 PMID:28267489 DOI: https://doi.org/10.1016/j.carbpol.2017.01.065

Bhat S, Shivakumar H. Bioadhesive controlled release clotrimazole vaginal tablets. Trop J Pharm Res. 2010;9:339-346. https://doi.org/10.4314/tjpr.v9i4.58924 DOI: https://doi.org/10.4314/tjpr.v9i4.58924

Gupta NV, Natasha S, Getyala A, Bhat RS. Bioadhesive vaginal tablets containing spray dried microspheres loaded with clotrimazole for treatment of vaginal candidiasis. Acta Pharm. 2013;63(3):359-372. https://doi.org/10.2478/acph-2013-0027 PMID:24152896 DOI: https://doi.org/10.2478/acph-2013-0027

Tunpanich P, Limpongsa E, Pongjanyakul T, Sripanidkulchai B, Jaipakdee N. Mucoadhesive sustained-release tablets for vaginal delivery of Curcuma comosa extracts: preparation and characterization. J Drug Deliv Sci Technol. 2019;51:559-568. https://doi.org/10.1016/j.jddst.2019.03.030 DOI: https://doi.org/10.1016/j.jddst.2019.03.030

Notario-Pérez F, Martín-Illana A, Cazorla-Luna R, et al. Influence of chitosan swelling behaviour on controlled release of tenofovir from mucoadhesive vaginal systems for prevention of sexual transmission of HIV. Mar Drugs. 2017;15(2):50. https://doi.org/10.3390/md15020050 PMID:28230790 DOI: https://doi.org/10.3390/md15020050

Perioli L, Ambrogi V, Pagano C, Scuota S, Rossi C. FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration. Int J Pharm. 2009;377(1-2):120-127. https://doi.org/10.1016/j.ijpharm.2009.05.016 PMID:19454304 DOI: https://doi.org/10.1016/j.ijpharm.2009.05.016

Kailasam P, Jamunadhevi V, Kaur G. Formulation and evaluation of once daily mucoadhesive vaginal tablet of metronidazole. Int J Res Pharm Sci. 2010;1:308-312. https://ijrps.com/index.php/home/article/view/2922

Fitaihi RA, Aleanizy FS, Elsamaligy S, Mahmoud HA, Bayomi MA. Role of chitosan on controlling the characteristics and antifungal activity of bioadhesive fluconazole vaginal tablets. Saudi Pharm J. 2018;26(2):151-161. https://doi.org/10.1016/j.jsps.2017.12.016 PMID:30166911 DOI: https://doi.org/10.1016/j.jsps.2017.12.016

Sánchez MT, Ruiz MA, Castán H, Morales ME. A novel double-layer mucoadhesive tablet containing probiotic strain for vaginal administration: Design, development and technological evaluation. Eur J Pharm Sci. 2018;112:63-70. https://doi.org/10.1016/j.ejps.2017.11.006 PMID:29129498 DOI: https://doi.org/10.1016/j.ejps.2017.11.006

Khan AB, Thakur RS. Design and evaluation of mucoadhesive vaginal tablets of tenofovir disoproxil fumarate for pre-exposure prophylaxis of HIV. Drug Dev Ind Pharm. 2018;44(3):472-483. https://doi.org/10.1080/03639045.2017.1399272 PMID:29082767 DOI: https://doi.org/10.1080/03639045.2017.1399272

El-Kamel A, Sokar M, Naggar V, Al Gamal S. Chitosan and sodium alginate-based bioadhesive vaginal tablets. AAPS PharmSci. 2002;4(4):E44. https://doi.org/10.1208/ps040444 PMID:12646014 DOI: https://doi.org/10.1208/ps040444

Baloglu E, Ay Senyıgıt Z, Karavana SY, et al. In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations. Chem Pharm Bull (Tokyo). 2011;59(8):952-958. https://doi.org/10.1248/cpb.59.952 PMID:21804238 DOI: https://doi.org/10.1248/cpb.59.952

Paczkowska M, Chanaj-Kaczmarek J, Romaniuk-Drapała A, et al. Mucoadhesive chitosan delivery system with Chelidonii herba lyophilized extract as a promising strategy for vaginitis treatment. J Clin Med. 2020;9(4):1208. https://doi.org/10.3390/jcm9041208 PMID:32331437 DOI: https://doi.org/10.3390/jcm9041208

Hani U, Shivakumar HG, Osmani RA, Srivastava A, Kumar Varma NS. Development of a curcumin bioadhesive monolithic tablet for treatment of vaginal candidiasis. Iran J Pharm Res. 2016;15(1):23-34. PMID:27610145

Shah RB, Tawakkul MA, Khan MA. Comparative evaluation of flow for pharmaceutical powders and granules. AAPS PharmSciTech. 2008;9(1):250-258. https://doi.org/10.1208/s12249-008-9046-8 PMID:18446489 DOI: https://doi.org/10.1208/s12249-008-9046-8

Jallo LJ, Ghoroi C, Gurumurthy L, Patel U, Davé RN. Improvement of flow and bulk density of pharmaceutical powders using surface modification. Int J Pharm. 2012;423(2):213-225. https://doi.org/10.1016/j.ijpharm.2011.12.012 PMID:22197769 DOI: https://doi.org/10.1016/j.ijpharm.2011.12.012

Beakawi Al-Hashemi HM, Baghabra Al-Amoudi OS. A review on the angle of repose of granular materials. Powder Technol. 2018;330:397-417. https://doi.org/10.1016/j.powtec.2018.02.003 DOI: https://doi.org/10.1016/j.powtec.2018.02.003

Cazorla-Luna R, Martín-Illana A, Notario-Pérez F, et al. Vaginal polyelectrolyte layer-by-layer films based on chitosan derivatives and Eudragit® S100 for pH responsive release of tenofovir. Mar Drugs. 2020;18(1):44. https://doi.org/10.3390/md18010044 PMID:31936439 DOI: https://doi.org/10.3390/md18010044

Notario-Pérez F, Cazorla-Luna R, Martín-Illana A, et al. Optimization of tenofovir release from mucoadhesive vaginal tablets by polymer combination to prevent sexual transmission of HIV. Carbohydr Polym. 2018;179:305-316. https://doi.org/10.1016/j.carbpol.2017.10.001 PMID:29111056 DOI: https://doi.org/10.1016/j.carbpol.2017.10.001

Jug M, Hafner A, Lovrić J, et al. An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems. J Pharm Biomed Anal. 2018;147:350-366. https://doi.org/10.1016/j.jpba.2017.06.072 PMID:28720350 DOI: https://doi.org/10.1016/j.jpba.2017.06.072

Palade L, Popovici I, Cojocaru I. In vitro evaluation of 5-fluorouracil dissolution profiles from vaginal bioadhesive tablets. Farmacia. 2013;61(4):640-647.

Baki G, Bajdik J, Kelemen A, Pintye-Hódi K. Formulation of a solid intravaginal matrix system to prolong the pH-decreasing effect of lactic acid. J Drug Deliv Sci Technol. 2009;19(2):133-137. https://doi.org/10.1016/S1773-2247(09)50021-4 DOI: https://doi.org/10.1016/S1773-2247(09)50021-4

Fernandes L, Costa R, Henriques M, Rodrigues ME. Simulated vaginal fluid: candida resistant strains’ biofilm characterization and vapor phase of essential oil effect. J Mycol Med. 2022;33(1):101329. https://doi.org/10.1016/j.mycmed.2022.101329 PMID:36270212 DOI: https://doi.org/10.1016/j.mycmed.2022.101329

Lupo N, Fodor B, Muhammad I, Yaqoob M, Matuszczak B, Bernkop-Schnürch A. Entirely S-protected chitosan: a promising mucoadhesive excipient for metronidazole vaginal tablets. Acta Biomater. 2017;64:106-115. https://doi.org/10.1016/j.actbio.2017.10.014 PMID:29030305 DOI: https://doi.org/10.1016/j.actbio.2017.10.014

Colombo N, Carinelli S, Colombo A, et al. ESMO Guidelines Working Group. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012; Suppl 7:vii27-32. https://doi.org/10.1093/annonc/mds268 PMID: 22997451 DOI: https://doi.org/10.1093/annonc/mds268

Perioli L, Ambrogi V, Pagano C, Massetti E, Rossi C. New solid mucoadhesive systems for benzydamine vaginal administration. Colloids Surf B Biointerfaces. 2011;84(2):413-420. https://doi.org/10.1016/j.colsurfb.2011.01.035 PMID:21354770 DOI: https://doi.org/10.1016/j.colsurfb.2011.01.035

Pendekal MS, Tegginamat PK. Hybrid drug delivery system for oropharyngeal, cervical and colorectal cancer—in vitro and in vivo evaluation. Saudi Pharm J. 2013;21(2):177-186. https://doi.org/10.1016/j.jsps.2012.07.002 PMID:23960833 DOI: https://doi.org/10.1016/j.jsps.2012.07.002

Owen DH, Katz DF. A vaginal fluid simulant. Contraception. 1999;59(2):91-95. https://doi.org/10.1016/S0010-7824(99)00010-4 PMID:10361623 DOI: https://doi.org/10.1016/S0010-7824(99)00010-4