CONTROLLED-RELEASE OF CONTRACEPTIVE STEROIDS FROM BIODEGRADABLE AND INJECTABLE GEL FORMULATIONS - IN-VIVO EVALUATION

Purpose. The purpose of this study was to investigate in vivo biocompa tibility, biodegradability and biological effects of contraceptive ste roids, such as levonorgestrel and ethinyl estradiol, released from gel s prepared with a combination of derivatized vegetable oil (Labrafil 1 944 CS) and glyceryl ester of fatty acids (Precirol ATO 5). Methods. B iocompatibility, biodegradability, and in vivo effects of levonorgestr el and ethinyl estradiol were studied by histologic evaluation of rat tissue, visual estimate of changes in gel size, and assessment of drug effects on reproductive cyclicity of female rats, respectively, follo wing subcutaneous injection of gel formulations. Results. Histological evaluation of the tissue samples following an injection of the gel re vealed an inflammatory reaction for about 7 days, after which the tiss ues did not show any inflammatory response. Complete degradation of th e gels containing 10% wax was observed between 5 and 6 weeks. Normal r at estrous cycles were completely blocked by the contraceptive steroid s released from the gels. Gel formulations containing 0.25% w/w levono rgestrel were more effective in blocking the estrous cycle of female r ats compared to the oil formulations containing an identical drug load ing. The duration of the biological effect induced by levonorgestrel a ppears to be dose-related. The gel formulation containing 2.00% ethiny l estradiol was superior to oil formulation containing an identical dr ug loading in terms of controlling drug release and toxicity. Conclusi ons. These observations suggest that Labrafil-Precirol gels are biocom patible and biodegradable. Moreover, controlled release of steroids is possible in vivo for a prolonged period of time.