Effect of excipient on drug release and permeation from silicone-based barrier devices

Abstract

Spermicide-releasing disposable vaginal devices were fabricated from silicone elastomer and evaluated for controlled release of Nonoxynol-9 (N-9). The optimal loading dose of N-9 in the diaphragm-shaped barrier device to achieve an appropriate release rate was of the order of 35%. Vaginal permeation of N-9 from disc-shape vaginal devices was negligible over the initial 5 h, and increased in a Q vs. t pattern. Several excipients were screened for spermicidal activity and for synergistic effects on the release rate of N-9 from diaphragm-shape barrier devices. Incorporation of a cosolvent, Dow Corning silicone fluid (SF), into the vaginal devices facilitated burst release of N-9, and consequently reduced the required loading dose of N-9. Addition of 10% of SF in diaphragms loaded with 25% of N-9 increased the release rate of N-9 to the equivalent of that from diaphragms loaded with 35% of N-9. SF increased the solubility of N-9 in silicone-based vaginal devices, but did not affect the permeation rate of N-9 through vaginal mucosa. Silicone-based barrier devices can achieve a controllable release rate of N-9 within vagina, as well as a controllable permeation rate of N-9 through vaginal mucosa, and therefore offer a promising approach for achieving fertility control.