Original research articleAssessing the potential of the Woman’s Condom for vaginal drug delivery
Introduction
PATH, with CONRAD and international research partners, used an iterative user-driven development process to design a female condom that is easy to use, is comfortable and provides good sensation for both partners. The resulting product, the Woman's Condom (Fig. 1), is safe and has good performance in clinical studies across multiple countries [1], [2], [3], [4], [5], [6]. The Woman’s Condom has been preferred over other female condoms for its ease of use, appearance and fit [2], [5]. In a multisite trial comparing new female condoms to the FC2 female condom, the Woman’s Condom showed performance similar to the FC2 female condom, with the same low rates of safety concerns [6].
The Woman’s Condom, manufactured by Dahua Medical Apparatus Company (Dahua, Shanghai, China), is approved by regulatory bodies in Europe, China, South Africa, Malawi and Zambia and is currently available in limited markets in China and South Africa. Expansion of access to this new multipurpose prevention technology (MPT) for protection from sexually transmitted infections (STIs), including HIV, and unintended pregnancy is under way.
The Woman’s Condom has several unique features. The thin, polyurethane pouch provides good sensation and comfort for both partners. The dissolving polyvinyl alcohol (PVA) capsule contains the condom pouch to facilitate handling and insertion. Once the capsule is inserted, it dissolves within 30–60 s, and the pouch unfolds inside the vagina. Although female condoms are designed to protect from both unintended pregnancy and STIs, exploring the feasibility of using this dissolving capsule as a vaginal drug delivery platform is of interest.
Several formulations and delivery platforms are under investigation for vaginal administration of drugs to prevent HIV and other STIs. These include gels, vaginal rings, cervical barriers such as diaphragms, tablets and polymeric films (Table 1). Multiple microbicide candidates have been formulated into vaginal films which provide discrete, easy-to-use, low-cost and stable platforms for drug delivery [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Marketed vaginal films include the Vaginal Contraceptive Film (VCF), VCF Lubricating Film and Vaginal Scented Film (Apothecus Pharmaceutical Corporation, Oyster Bay, NY, USA). One main polymer used in films, as well as in the polymer capsule of the Woman’s Condom, is PVA. Additional examples of combination chemical and physical barriers for multipurpose prevention include Acidform gel and BufferGel, both used with a diaphragm [17], [18], BufferGel Duet™ [19] and a microbicide-releasing SILCS diaphragm [20].
UC781 (thiocarboxanilide, N-[4-chloro-3-(3-methyl-2-butenyloxy) phenyl]-2-methyl-3-furancarbothioamide) is a tight-binding non-nucleoside reverse transcriptase inhibitor (NNRTI) that has favorable anti-HIV-1 properties in vitro [21], [22], [23], [24]. UC781 has been formulated within several dosage platforms including gel [25], [26], [27], vaginal ring [28] and vaginal film [12]. Prior to and during the time of our studies, UC781 was a leading microbicide candidate, which is a reason for its utilization. However, further pursuit of a UC781 microbicide has ceased. Although UC781 is no longer under development as a vaginal microbicide candidate, it is a model compound representative of many hydrophobic small molecule NNRTIs which are under development for HIV prevention in preclinical and clinical stages.
In this preclinical study, UC781 was added to polymeric capsules to illustrate the feasibility of incorporating a microbicide candidate into the Woman’s Condom product. As a combined physical barrier and drug delivery platform, the Woman’s Condom could provide an alternative method for delivery of drugs relevant for women’s sexual and reproductive health, including long-acting HIV prevention drugs that could provide added protection for subsequent acts of sex if no preventative method is used.
Section snippets
Materials
UC781 was supplied by CONRAD. PVA, polyethylene glycol (PEG) 400, PEG 600, glycerin and propylene glycol were purchased from Spectrum (New Brunswick, NJ, USA). PEG 4000 was supplied by the Dow Chemical Company (Midland, MI, USA), and hydroxypropyl methylcellulose (HPMC K4M; Methocel®) was supplied by Colorcon (Harleysville, PA, USA). Woman’s Condom samples were provided by PATH (manufactured by Dahua). A MilliQ (Millipore, Milford, MA, USA) water filtration system operating at 18.2 MΩ cm was
Capsule formulation development
Two polymeric platforms were identified for incorporation of UC781. The flow diagram (Supplemental Fig. 1) depicts the process by which the PVA-based platform was chosen. Viscosity issues or peeling difficulties caused the 10%, 15%, 18% and 20% PVA platforms to fail. The 12.5% PVA polymeric platform (Supplemental Table 1) was selected as platform 1 since it was compatible with every step of the process. PEG 400 was utilized for UC781 dispersion. A multipolymeric platform (Supplemental Table 2)
Discussion
This proof-of-concept study illustrates the feasibility of incorporating a microbicide candidate, UC781, into a polymeric capsule of the Woman’s Condom. Two capsule platforms were developed and underwent chemical and physical assessments for pharmaceutical product development. Capsule masses, disintegration times and puncture strength values varied across platforms due to polymer and other excipient differences. Platform 1 and Woman’s Condom capsules mainly contain PVA. Consequently, their
Acknowledgments
We would like to thank Tiantian Gong and Sheila Grab for providing manufacturing and analytical support and Kevin Uranker for the TZM-bl cellular assessments (all of Magee-Womens Research Institute). We would like to thank Hrushikesh Agashe and Sheila Grab of Magee-Womens Research Institute and Maggie Kilbourne-Brook and Laura East of PATH for assistance in reviewing this manuscript. Funding for this research was made possible by the generous support of the American people through the United
References (31)
- et al.
Short-term acceptability of the PATH Woman's Condom among couples at three sites
Contraception
(2006) - et al.
Comparative crossover study of the PATH Woman's Condom and the FC Female Condom
Contraception
(2008) - et al.
Three new female condoms: which do South-African women prefer?
Contraception
(2011) - et al.
Performance and safety of the second-generation female condom (FC2) versus the Woman's Condom, the VA worn-of-women, and the Cupid female condoms: a randomised controlled non-inferiority crossover trial
Lancet Glob Health
(2013) - et al.
The physicodynamic properties of mucoadhesive polymeric films developed as female controlled drug delivery system
Int J Pharm
(2006) - et al.
A phase I study of the functional performance, safety and acceptability of the BufferGel Duet
Contraception
(2008) - et al.
Testing of viscous anti-HIV microbicides using Lactobacillus
J Microbiol Methods
(2012) - et al.
Performance of the Woman's Condom among couples in Shanghai, China
Eur J Contracept Reprod Health Care
(2012) - et al.
Initial reactions to the Woman's Condom by potential user groups in Shanghai, China
J Fam Plann Reprod Health Care
(2013) - et al.
Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120
BMC Infect Dis
(2001)
Water dispersible microbicidal cellulose acetate phthalate film
BMC Infect Dis
Biocompatibility of solid-dosage forms of anti-human immunodeficiency virus type 1 microbicides with the human cervicovaginal mucosa modeled ex vivo
Antimicrob Agents Chemother
Prolong release bioadhesive vaginal film of anti-HIV drug (zidovudine): formulation and in-vitro evaluation
Int J Pharm Sci Res
UC781 polymeric thin films — optimization and stability assessment
Development and characterization of a vaginal film containing dapivirine, a non- nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission
Drug Deliv Transl Res
Cited by (6)
Women-specific routes of administration for drugs: A critical overview
2021, Advanced Drug Delivery ReviewsCitation Excerpt :The drug was incorporated in the polyoxymethylene spring core of the diaphragm during manufacturing (Fig. 6), and the system was shown able to provide zero-order release kinetics in vitro. In another example, Kramzer et al. [188] demonstrated the feasibility of modifying a female condom with the NNRTI UC781 by incorporating the drug into the polymeric capsule used for insertion of the device. The vaginal route may be further used for focal drug delivery targeting well-defined areas, most notably the cervix.
Acceptability of the Woman's Condom in a phase III multicenter open-label study
2019, ContraceptionCitation Excerpt :However, not every woman wants a LARC or a hormonal contraceptive; the potential for STI and HIV protection makes internal condoms one of few methods that can offer dual protection. In addition, the WC holds promise for vaginal delivery of HIV and STI prevention medications [30]. Female-controlled methods that can protect against STI, HIV and pregnancy would be a boon.
Pipeline for contraceptive development
2016, Fertility and SterilityCitation Excerpt :Early-phase clinical studies of the rings are ongoing. Potential barrier methods include the SILCS diaphragm, combined with active antiviral agents such as Tenofovir gel (42) and the new Women's Condom (45), both developed by the Program for Appropriate Technology in Health. Male condoms are the only reversible contraceptive methods available to men.
A novel method to enhance efficacy of topical drugs by condom occlusion in penile dermatoses
2020, Postgraduate Medical JournalHIV and contraception
2017, Current Opinion in Obstetrics and GynecologyAn update on multipurpose prevention technologies for the prevention of HIV transmission and pregnancy
2016, Expert Opinion on Drug Delivery