孕酮微胶囊冻干工艺的优化及其体外释放研究OA

In order to optimize the vacuum freeze-drying process of progesterone microcapsules and evaluate their in vitro release characteristics,the protective effects of key freeze-drying parameters on progesterone microcapsules were systematically investigated.The pre-freezing time gradient(2,4,6,8 and 12 h)and pre-freezing temperature gradient(-20 and 80℃)were set up,and sucrose,glucose and lactose with different concentrations(3.0%,5.0%and 7.5%,respectively)were selected as freeze-drying protective agents to screen the best pre-freezing conditions and freeze-drying protective agents.The core quality indicators such as appearance,redispersibility,reconstitution time encapsulation efficiency and drug loading of progesterone microcapsules were comprehensively evaluated.At the same time,the three-stage in vitro digestion model(rumen fluid-gastric fluid-small intestinal fluid)of simulated ruminants was used to evaluate its stability and targeted release.The results showed that under the conditions of pre-freezing time of 8 h and pre-freezing temperature of-80℃,the progesterone microcapsules had a smooth and full appearance,few bubbles and no splashing.When 3.0%lactose was added as a protective agent,the structure of progesterone microcapsules was loose and porous;the encapsulation rate was 96.68%,and the drug loading was 19.97%,which was significantly higher than that of the blank control(P<0.05).The cumulative release rates of progesterone microcapsules in simulated rumen fluid and gastric fluid within 24 h were only 28.74%and 29.15%,respectively,while the cumulative release rate in simulated intestinal fluid within 10 h was 80.61%,showing good rumen-stomach protection and small intestine targeted release characteristics.The results showed that the optimized process(pre-freezing temperature was-80℃,pre-freezing time was 8 h,and freeze-dried protective agent was 3.0%lactose)established in this study could prepare freeze-dried progesterone microcapsules with excellent performance,which provided an important basis for the development of estrus synchronization oral preparations for ruminants.