Preparation And Influencing Factors Of Bioequivalence Of Progesterone Sustained-release Gel In Vitro

The lack of pregnancy-related hormone levels in the human body is one of the main causes of high abortion rates.Progesterone,which maintains normal levels in the blood,is an essential condition for pregnancy.In the treatment of clinically relevant diseases,such as assisted reproductive technology,the secretion of hormones from the body will be inhibited,and the application of corresponding supporting techniques can effectively regulate hormone levels and ensure the health of the body during treatment.Vaginal delivery systems have been widely used and commonly used dosage forms include tablets,suppositories,capsules and gels.The vaginal administration method can avoid the liver first pass effect,has high bioavailability,can be self-administered,is convenient and quick,does not cause trauma,and improves patient compliance.Progesterone vaginal sustained release gel can continuously adhere to the drug site to 72 h,slow release of drugs,long-lasting effect,stable efficacy,can effectively increase the level of hormones in the body.This article uses progesterone as a model drug to study the optimization of progesterone vaginal sustained release Gel preparation and bioequivalence prediction studies.In this study,a ball mill was used to prepare micronized progesterone drug substance,and the drug could be uniformly dispersed in the formulation matrix.The evaluation indicators of the preparations were appearance traits,physical stability,particle size,and release rate.The results of the formulation optimization study showed that the similarity factor of the dissolution release curve was 34 type for the mixed formulation of the 34 type mixed glycerol and the reference formulation.71.61,that the release behavior is consistent,the content of glycerol has a greater impact on the release behavior of the gel.In the optimization of the preparation process parameters for the small-scale test,the gel was prepared by mechanical stirring.The results showed that the stirring speed was 160 rpm and the hydration time was 100 min.A homogeneous and viscous aqueous phase matrix was obtained.The emulsification stirring speed was 50 rpm and the emulsification time was 20 min.The gel obtained was uniform and delicate,consistent with the release behavior of the reference preparation,and provided the basis for further experiments related to the formulation in vivo.With reference to the Chinese Pharmacopoeia(Fourth Part of 2015)and guidelines for quality research,the quality and stability of progesterone sustained-release gels were studied.The results showed that the quality of the preparation was controllable,and its content and release were in compliance with the regulations.The factors affected were high temperature(60 °C),high humidity(relative humidity 90 % ± 5 %)and light(4500 Lx ± 500 Lx)tests.In order to generate new impurities,the original impurity content is basically unchanged,and the properties are stable.However,under high temperature conditions,the appearance of the formulation changes slightly,the gel dehydrates and dries,and turns slightly yellow.Therefore,the progesterone gel should be placed in a cool shade.Or at room temperature,sealed from light.According to the Chinese Pharmacopoeia(Fourth Part of 2015),guidelines for human bioavailability and bioequivalence testing of pharmaceutical preparations,and in vitro transmembrane experiments of preparations,the preliminary prediction research content of bioequivalence experiments.