PURPOSE: To design a flux controlled pump (FCP) capable of 30-day, controlled release of macromolecules to the vaginal mucosa. METHODS: 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. RESULTS: 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 30 days with an average release rate of 24 ± 2 μg/day (mean ± SD) and range of 16 to 42 μg/day. We observed a slightly lower average release rate in vivo of 20 ± 0.6 μg/day (mean ± SD). CONCLUSIONS: 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.
PURPOSE: To design a flux controlled pump (FCP) capable of 30-day, controlled release of macromolecules to the vaginal mucosa. METHODS: 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. RESULTS: 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 30 days with an average release rate of 24 ± 2 μg/day (mean ± SD) and range of 16 to 42 μg/day. We observed a slightly lower average release rate in vivo of 20 ± 0.6 μg/day (mean ± SD). CONCLUSIONS: 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.
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