Intravaginal flux controlled pump for sustained release of macromolecules.

Abstract

To design a flux controlled pump (FCP) capable of 30-day, controlled release of macromolecules to the vaginal mucosa. The FCP is composed of a single chamber fabricated from a rigid thermoplastic with orifices and encloses a pellet of water-swellable polymer containing the drug substance. We performed testing both in vitro and in rabbits. To ensure vaginal retention in the rabbit, we designed and attached an oval shape-memory polyether urethane retainer to the FCP allowing for long-term intravaginal evaluation of a solid dosage form without invasive surgical implantation. The orifices and swelling properties of the polymer pellet control water entry for polymer hydration and expansion, and subsequent extrusion of the drug-containing gel from the orifice. A FCP device containing a pellet composed of hydroxypropyl cellulose compounded with a model macromolecule, achieved controlled in vitro release for 30days with an average release rate of 24 ± 2μg/day (mean ± SD) and range of 16 to 42μg/day. We observed a slightly lower average release rate in vivo of 20 ± 0.6μg/day (mean ± SD). The size of the orifice and nature of the swelling polymer controls the hydration rate and thereby macromolecule release rate and duration from this FCP.