Pharmaceutical Research Of Sustained-release Progesterone Vaginal Gel

Normal luteal function is essential to maintain pregnancy and embryo implantation.The controlled ovarian stimulation and follicular aspiration in assisted reproductive technology will reduce hormone levels luteal phase, resulting in luteal insufficiency, pregnancy rate decreased and the abortion rate increased, more effective treatment. So luteal support in assisted reproductive technology has become conventional therapy. In order to provide luteal support effectively, recreasing the systemic side effects, improving patient compliance, the formulation, preparation procedure and quality standards of the progesterone vaginal sustained-release gel was studied.On the base of the formula and adjuvant’s property of correlative product inabroad, the formulation of sustained-release progesterone vaginal gel was determined. Using micro-phase structure, in vitro release and dynamic viscosity as index, the composition and preparation procedure of progesterone gel were optimized. The sustained-release progesterone vaginal gel containing 8% (w/w) micronized progesterone in an oil-in-water emulsion on a polycarbophil base, delivered via a special applicator. The polycarbophil base ensures that the gel adheres to the vaginal epithelium,while the emulsion provides an oily depot from which progesterone is continuously released into the aqueous phase and hence into the tissue. Using the mixed shearing process,the exquisiteand white progesterone gel can be prepared. Under the same release conditions, the similarity factor f2 of the release profile between sample and control was 74.82, greater than 50, showing no difference.According to the Chinese Pharmacopoeia (2015) and the technical guidance from CDE, the gel quality control methods were established, including the determination of drugs content, the determination of related substances, the test of microorganisms and the conditions of dissolution experiments. We established a microbiological examination method using the plate method to carry out technical inspections of bacteria, fungi and mold count checked. The recoveries of microbiological examination within a range of 0.5 to 2.0, are applied to progesterone gel. It provided a basis for the establishment of quality standards of sustained-release progesterone vaginal gel.Finally, the stability of progesterone gel were studied. The Stress testing showed that progesterone gel was stable and no new impurities appeared in high temperature (60℃), humidity (RH90%±5%), bright light(4500 1x±500 lx) conditions. However, at high temperatures, gel will dry, it may be partly caused by water evaporation. The gel placed at 30℃, RH65% for 2 months,the character, content and related substances did not change significantly, the cumulative release rate of every time point was no significant difference. The subsequent stability test still in progress. Referring to the test results and Crinone(?) storage conditions, sustained-release progesterone gel should be stored sealed, lower than 25 ℃ environment.