Design and evaluation of mucoadhesive vaginal tablets of tenofovir disoproxil fumarate for pre-exposure prophylaxis of HIV

Abstract

Objective: To design and evaluate novel, feasible, safe, mucoadhesive intravaginal tablets of tenofovir disoproxil fumarate (TDF).

Significance: It may provide pre-exposure prophylaxis for women against HIV.

Methods: TDF intravaginal tablets were formulated employing poylvinylpyrrolidone (PVP) as the matrix forming polymer and various mucoadhesive polymers such as carbopol 934, 940, chitosan, and sodium carboxymethylcellulose (SCMC). Wet granulation was used. The evaluation involved testing drug-excipient compatibility, precompression parameters such as percentage yield, bulk density and tapped density of the granules, Carr’s index, Hausner ratio, angle of repose, post compression parameters such as color, shape, physical dimensions, weight variation, hardness, friability, swelling index, assay, in vitro dissolution study and ex vivo mucoadhesion studies.

Results: Based on in vitro evaluation, C1 was selected as the best formulation and evaluated further for release kinetics, curve fitting analysis, absorption studies using liquid chromatography-mass spectrometry (LC-MS) technique and histopathological assessment in female Sprague–Dawley rats. C1 followed Higuchi model kinetics. Accelerated stability study was as per ICH guidelines by keeping C1 at 40 ± 2 °C and 75 ± 5% RH for six months.

Conclusions: C1 was selected as the best formulation due to better swelling index (65.93% at 24 h), prolonged release of 100.62% cumulative drug release (CDR) at 24 h, superior mucoadhesion force (35.93 × 10² dynes/cm²) and retention time (16 h). The study revealed that C1 remained stable for six months. C1 showed nil systemic absorption which is desirable and according to histopathological study, C1, exhibited minimal damage on the rat vaginal epithelium indicating safety.

Keywords:

• AIDS
• HIV
• histopathology
• in vivo absorption studies
• intravaginal tablets
• mucoadhesion
• tenofovir disoproxil fumarate

Acknowledgements

The authors thank the Principal and management of Krupanidhi College of Pharmacy, Bangalore for extending Laboratory and other facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Research Grant (Ref.No. 8023/RID/RPS-72/(POLICYIII) (PVT)/2011–12 from All India Council for Technical Education is sincerely acknowledged.