[Study on compound levonorgestrel microspheres].

Levonorgestrel (LNG) and estradiol (E2) were mixed in the ratio of 5:2 by weight. Compound LNG gelatin-microspheres were prepared by phase-separation method, natural biodegradable gelatin being used as the core material. The experimental conditions were optimized, the mean diameter of the microspheres obtained being 10-40 microns, and the rate of encapsulation 65-75%. Storage observations and acceleration tests of the compound LNG gelatin-microsphere injection prepared showed that the microspheres have good stability. The thermal degradation activation energy of the injection was determined to be 134.4 kJ/mol, based on differential scanning colorimetry (DSC). T1/2 values for dissolution in vitro of LNG and E2 from the compound LNG gelatin-microsphere injection and from the unencapsulated injection showed significant difference (P < 0.01), indicating that the microspheres have good sustained release action. Effects of the pure LNG microsphere injection and compound LNG microsphere injection on the mouse ovary were compared histologically. The results showed that the compound LNG microsphere injection reduced some of the side effects such as ovary congestion. This points out that the compound dosage form can clinically alleviate the irregular bleeding caused by the administration of LNG alone.