Intravaginal flux controlled pump for sustained release of macromolecules.
OBJECTIVE
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.
Department of Bioengineering, University of Utah, 20 S 2030 E, Salt Lake City, Utah, 84112, USA.
Ryan S
RS
Teller
Rachna
R
Rastogi
Todd J
TJ
Johnson
Michael J
MJ
Blair
Robert W
RW
Hitchcock
Patrick F
PF
Kiser
D000282:Administration, Intravaginal; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003911:Dextrans / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000295:instrumentation*; D065546:Drug Liberation; D004867:Equipment Design; D005260:Female; D007328:Insulin / Q000008:administration & dosage; D011140:Polyurethanes / Q000737:chemistry; D011817:Rabbits; D012235:Rhodamines / Q000008:administration & dosage; D014867:Water / Q000737:chemistry
D003692:Delayed-Action Preparations; D003911:Dextrans; D007328:Insulin; D011140:Polyurethanes; D012235:Rhodamines; C115016:polyetherurethane; C051311:rhodamine dextran; D014867:Water; D002482:Cellulose; C008079:hydroxypropylcellulose