Use of a hydrophilic excipient to modulate the release of dapivirine, copper ions and zinc ions from a matrix-type vaginal ring

Two major challenges for developers of drug-releasing vaginal rings are (i) the formulation and release of hydrophilic water-soluble actives, which generally require novel ring designs, very high drug loadings, and/or inclusion of substances to modify the release mechanism and enhance release, and (ii) the incorporation and release of multiple actives, particularly when the actives have very different solubility/permeability characteristics. In this study, as part of ongoing efforts to develop inexpensive and easily-manufactured multipurpose vaginal rings for HIV prevention, non-hormonal contraception, and prevention of bacterial and viral sexually transmitted infections, we describe formulation development and testing of matrix-type silicone elastomer rings containing combinations of three actives—dapivirine (D), copper sulfate anhydrous (C), and zinc sulfate monohydrate (Z)—and the hydrophilic excipient hydroxypropyl methylcellulose (H). Inclusion of H significantly impacted in vitro release and the properties of the vaginal rings, including mechanical performance, ring dimensions, and swelling. Preliminary testing of a lead candidate triple-active DCZH ring prototype showed good stability.