New long-acting injectable microcapsule contraceptive system.

ABSTRACT

PIP: A new, long-acting, injectable contraceptive system which uses a biodegradable polymer (d,1-polylactic acid) in the form of microspheres for controlled delivery of norethisterone is described. The continuous controlled release is designed to last exactly 6 months after a single intramuscular injection. System fabrication has yielded a prototype: Microcapsules of the biodegradable polymer containing homogeneously dispersed micronized crystals of norethisterone are injected, and the steroid is released slowly at a rate of .9 mcg of norethisterone/day/mg of microcapsule by diffusion of the drug through the polymer matrix. Pharmacokinetics of the injectable system of norethisterone were tested in normally cycling female baboons. 3 different doses of a standard preparation were tested (4-5 animals/group). After injection of either 300, 200, or 100 mg of microcapsules of 75, 50, or 25 mg of norethisterone, blood samples were collected and analyzed for the steriod, estrogen, and progesterone; radioimmunoassay of samples collected at selected intervals was carried out. For 6 months after injection, all 3 doses were parallel. Ovulation was inhibited in all baboons for 6 months after treatment; each animal resumed normal ovarian function within 1-2 weeks after the norethisterone blood level fell below the level of detection of the assay system (10-25 pg/ml).