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.
- in vivo evaluation
- non-surgical implantation
- vaginal delivery
ASJC Scopus subject areas
- Molecular Medicine
- Pharmaceutical Science
- Organic Chemistry
- Pharmacology (medical)