Assessing the potential of the Woman’s Condom for vaginal drug delivery

Abstract

Background

The Woman’s Condom is a new female condom that uses a dissolvable polyvinyl alcohol capsule to simplify vaginal insertion. This preclinical study assessed the feasibility to incorporate an antiviral drug, UC781, into the Woman’s Condom capsule, offering a unique drug delivery platform.

Study design

UC781 capsules were fabricated using methods from the development of the Woman’s Condom capsules as well as those used in vaginal film development. Capsules were characterized to evaluate physical/chemical attributes, Lactobacillus compatibility, in vitro safety and bioactivity, and condom compatibility.

Results

Two UC781 capsule platforms were assessed. Capsule masses (mg; mean±SD) for platforms 1 and 2 were 116.50±18.22 and 93.80±8.49, respectively. Thicknesses were 0.0034±0.0004 in and 0.0033±0.0004 in. Disintegration times were 11±3 s and 5±1 s. Puncture strengths were 21.72±3.30 N and 4.02±0.83 N. Water content measured 6.98±1.17% and 7.04±1.92%. UC781 content was 0.59±0.05 mg and 0.77±0.11 mg. Both platforms retained in vitro bioactivity and were nontoxic to TZM-bl cells and Lactobacillus. Short-term storage of UC781 capsules with the Woman’s Condom pouch did not decrease condom mechanical integrity.

Conclusions

UC781 was loaded into a polymeric capsule similar to that of the Woman’s Condom product. This study highlights the potential use of the Woman’s Condom as a platform for vaginal delivery of drugs relevant to sexual/reproductive health, including those for short- or long-acting HIV prevention.

Implications

We determined the proof-of-concept feasibility of incorporation of an HIV-preventative microbicide into the Woman’s Condom capsule. This study highlights various in vitro physical and chemical evaluations as well as bioactivity and safety assessments necessary for vaginal product development related to female sexual and reproductive health.

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.