An injectable sustained release fertility control system

Abstract

An injectable composition to deliver the contraceptive steroid norethisterone at a sustained level for 90 days was prepared and tested. The delivery system, a physical matrix of poly-L(+)-lactic acid and 20% by weight steroid, was administered by conventional intramuscular injection into the lower hind limb of rats. Ten mg of cryogenically ground particles of 90–180μ and 180–250μ size, suspended in 0.1 ml of 1% methyl cellulose, were injected through 20 and 18 Stubbs gauge needles, respectively. A sample of particles of 180–250μ size was coated with pure poly-dl-lactic acid and tested. Measurement of the 14 C label from norethisterone excreted in urine and feces indicated apparent zero-order release for most of the 90-day test period. An initial high release of steroid was noted for all three systems tested. In addition, a final burst of steroid was noted for the 90–180μ system as apparently the remaining polymer broke down 88 days post-injection. From virtually none to 18% of the original 14 C labeled material was found to remain at the injection site at the end of the 90 days. There was no evidence of tissue irritation or encapsulation.