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Formulation and Characterization of Polymeric Films Containing Combinations of Antiretrovirals (ARVs) for HIV Prevention

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Abstract

Purpose

To develop polymeric films containing dual combinations of anti-HIV drug candidate tenofovir, maraviroc and dapivirine for vaginal application as topical microbicides.

Methods

A solvent casting method was used to manufacture the films. Solid phase solubility was used to identify potential polymers for use in the film formulation. Physical and chemical properties (such as water content, puncture strength and in vitro release) and product stability were determined. The bioactivity of the film products against HIV was assessed using the TZM-bl assay and a cervical explant model.

Results

Polymers identified from the solid phase solubility study maintained tenofovir and maraviroc in an amorphous state and prevented drug crystallization. Three combination film products were developed using cellulose polymers and polyvinyl alcohol. The residual water content in all films was <10% (w/w). All films delivered the active agents with release of >50% of film drug content within 30 min. Stability testing confirmed that the combination film products were stable for 12 months at ambient temperature and 6 months under stressed conditions. Antiviral activity was confirmed in TZM-bl and cervical explant models.

Conclusions

Polymeric films can be used as a stable dosage form for the delivery of antiretroviral combinations as microbicides.

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Abbreviations

ARVs:

Antiretrovirals

AZT:

Zidovudine

DPV:

Dapivirine

HAART:

Highly antiretroviral active therapy

HEC:

Hydroxy ethyl cellulose

HPMC:

Hydroxy propyl methyl cellulose

IHC:

Immunohistochemical

MVC:

Maraviroc

Na CMC:

Carboxy methyl cellulose sodium

PEG:

Poly ethylene glycol

PVA:

Poly vinyl alcohol

PVP:

Poly vinyl pyrrolidone

SMST:

Standard microbicide safety test

SPE:

Solid phase extraction

STIs:

Sexual transmitted infections

tBAHS:

t-Butylammonium bisulfate

TFA:

Triflouro acetic acid

TFV:

Tenofovir

UHPLC:

Ultra high pressure liquid chromatography

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ACKNOWLEDGMENTS AND DISCLOSURES

The work presented was supported through a grant from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institute of Health (AI082639) and the International Partnership for Microbicides (IPM). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA

    Ayman Akil, Hrushikesh Agashe, Yuan Shi & Lisa Cencia Rohan

  2. Department of Obstetrics and Gynecology and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Charlene S. Dezzutti, Bernard J. Moncla, Sharon L. Hillier & Lisa Cencia Rohan

  3. Magee-Womens Research Institute, 204 Craft Ave, B509, Pittsburgh, PA, 15213, USA

    Ayman Akil, Hrushikesh Agashe, Charlene S. Dezzutti, Bernard J. Moncla, Sharon L. Hillier, Yuan Shi, Kevin Uranker & Lisa Cencia Rohan

  4. International Partnership for Microbicides, Silver Spring, MD, USA

    Brid Devlin

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  1. Ayman Akil
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Correspondence to Lisa Cencia Rohan.

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Akil, A., Agashe, H., Dezzutti, C.S. et al. Formulation and Characterization of Polymeric Films Containing Combinations of Antiretrovirals (ARVs) for HIV Prevention. Pharm Res 32, 458–468 (2015). https://doi.org/10.1007/s11095-014-1474-4

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  • DOI: https://doi.org/10.1007/s11095-014-1474-4

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