Controlling the hydration rate of a hydrophilic matrix in the core of an intravaginal ring determines antiretroviral...

Intravaginal ring technology is generally limited to releasing low molecular weight species that can diffuse through the ring elastomer. To increase the diversity of drugs that can be delivered from intravaginal rings, we designed an IVR that contains a drug matrix encapsulated in the core of the IVR whereby the mechanism of drug release is uncoupled from the interaction of the drug with the ring elastomer. We call the device a flux controlled pump, and it is comprised of compressed pellets of a mixture of drug and hydroxypropyl cellulose within the hollow core of the ring. The pump orifice size and chemistry of the polymer pellets control the rate of hydration and diffusion of the drug-containing hydroxypropyl cellulose gel from the device. A mechanistic model describing the hydration and diffusion of the hydroxypropyl cellulose matrix is presented. Good agreement between the quantitative model predictions and the experimental studies of drug release was obtained. We achieved controlled release rates of multiple antiretrovirals ranging from μg/d to mg/d by altering the orifice design, drug loading, and mass of pellets loaded in the device. This device could provide an adaptable platform for the vaginal drug delivery of many molecules.