Use of hydrophilic pharmaceutical excipients to modulate release of metal ions from silicone elastomers.

Abstract

Silicone elastomers based on polydimethylsiloxane are biocompatible and non-biodegradable thermosetting polymers used in various drug delivery applications, including subdermal implants, vaginal rings, and intrauterine devices. Without exception, all marketed silicone elastomer drug delivery products provide sustained or controlled release of highly hydrophobic small drug molecules, since drug solubility in the silicone matrix is a prerequisite for molecular diffusion and release. We are interested in developing multipurpose silicone elastomer vaginal rings for local administration of metal ions-such as copper and zinc-for non-hormonal contraception and antimicrobial therapy. However, sustained/controlled release of metal ions from silicone elastomers containing metal nanopowders or metal salts is challenging due to their limited solubility in silicone. In this study, we assess the potential for enhancing the release of copper or zinc ions from silicone elastomer devices by co-formulating copper nanopowder, zinc nanopowder, copper sulfate, or zinc acetate with four common pharmaceutical excipients-gelatin, polyvinylpyrrolidone, sucrose, and hydroxypropyl methylcellulose. The study demonstrates that (i) copper/zinc nanopowders and salts can be successfully incorporated into addition-cure silicone elastomers, (ii) in vitro release of Cu²⁺/Zn² ions from silicone elastomers loaded with divalent salts was ∼100 times greater compared to nanopowders; (iii) incorporation of gelatin, polyvinylpyrrolidone, sucrose and hydroxypropyl methylcellulose significantly enhanced the release of Cu²⁺/Zn²⁺ ions (up to ∼30-fold), and (iv) enhanced release was due to water absorption into the silicone elastomer devices, causing swelling of the devices to an extent proportional to the excipient loading.