A new long-acting injectable microcapsule system for the administration of progesterone

Abstract

A long-acting injectable microcapsule system for the controlled-release systemic administration of progesterone (P4) is described. The system consists of microcapsules made of the biodegradable polymer, d,l-polylactic acid, which contain crystalline P4. Following injection, P4 is released from the microcapsules by diffusion and biodegradation of the polymer matrix. The rate of P4 release from the prototype microcapsule system in vivo is 1.3 microgram of P4/day/mg of microcapsules, and the duration of release is 30 days. Vaginal estrous cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following a single injection of P4 microcapsules. The effects of continuous progesterone therapy on reproductive function in both rats and baboons are dose-dependent. The utility of the system as a once-a-month injectable contraceptive is established in the baboon model.

PIP: A longacting injectable microcapsule system for the controlled-release systemic administration of progesterone is described and photographed. The microcapsules are made of biodegradable polymer which contain crystalline progesterone. After injection, the progesterone is released over time from the microcapsules by diffusion and biodegradation of the polymer matrix. Rats and baboons were used to evaluate the in vivo rates of progesterone release from different capsule preparations. Results are graphed and tabulated. Tests showed that 50% of the progesterone is available for quick release while the other 50% remains to be released at a slower rate. Smaller microcapsules released the progesterone at a greater rate and a shorter duration. By using larger microcapules, it should be possible to extend the useful duration of the microcapsule system. Vaginal estrus cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following injection of the progesterone microcapsules. This method of delivery has the advantages that it obviates cyclic overdosing and underdosing and it can be delivered both locally and systemically.