ORCID

0000-0002-3837-1777 (Agrahari), 0009-0008-6637-5290 (Peet), 0000-0002-4476-8287 (Clark), 0009-0009-9641-1325 (Doncel)

Document Type

Article

Publication Date

2026

DOI

10.1208/s12249-026-03427-1

Publication Title

AAPS PharmSciTech

Volume

27

Issue

4

Pages

204

Abstract

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 mg) and elvitegravir (EVG; 16 mg) to target both bacterial STIs and HIV. Inserts were manufactured using a simple and cost-effective process. Drug loading was within 95-105% of the labeled amount, confirming a robust manufacturing process. In vitro, the inserts disintegrated within 10 min with > 95% drug release within 60 min. The dissolution behavior of DOX inserts showed surface erosion but was affected by medium volume and drug amount. The inserts met key physicochemical targets: hardness (5-8 kg), friability (<  1%), moisture content (<  2%), and osmolality (<  550 mOsm/kg). Based on 6-month storage stability, DOX inserts maintained their physicochemical properties, indicating a shelf life of > 2 years. Preliminary 1-month stability of TED inserts under accelerated conditions showed preservation of their physicochemical properties. These data describe the formulation development and in vitro characterization of topical inserts containing DOX alone or in combination with antiretrovirals (TAF and EVG). Both inserts offer a novel, on-demand topical STI prevention option that supports flexible PrEP/PEP use by both women and men.

Rights

© The Authors 2026.

This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Data Availability

Article states: "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request."

Original Publication Citation

Agrahari, V., Peet, M. M., Monpara, J., John, R., Jonnalagadda, S., Gupta, P. K., Clark, M. R., & Doncel, G. F. (2026). Formulation development of topical inserts containing doxycycline and doxycycline combined with tenofovir alafenamide and elvitegravir for the prevention of sexually transmitted infections. AAPS PharmSciTech, 27(4), Article 204. https://doi.org/10.1208/s12249-026-03427-1

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