Preparation And Evaluation Of Self-microemulsifying Capsule For Candesartan Cilexetile

Candesartan cilexetile has a special chemical structure , effectively cures hypertension. It is the low aqueous solubility of such compounds,which leads to poor oral bilavailability. Candesartan cilexetile tablet can be found in the market, because of its low bioavailability, we try to invent new type of formulation which is low poisonous and high bioavailability on the basic. Self- Microemulsifying drug delivery system are described as mixtures of oil, emulsifier, co-emulsifier and drug. The principal characteristic of these systems form fine oil-in-water microemulsions upon mild agitation following diluted by aqueous phase, with mean droplet size less than 100nm. SMEDDS can improve the bioavailability and the absorption of poorly soluble drugs, and broaden the group of people.In this study, candesartan cilexetile was selected as the model drug for the self-Microemulsifying drug delivery system(SMEDDS) administration. The purpose is to invent a new capsule which is high bioavailability in vivo. The main contents and conclusions in this study were as follows:1.Pre-formulation studies of candesartan cilexetile were carried out. HPLC method was built to measure the contents of candesartan cilexetile. The solubilities of candesartan cilexetile in different oil, emulsifier and co-emulsifier were measured. The solubility of candesartan cilexetile was the most in Cremophor RH40. According to orthogonal test in blank SMEDDS , the optimal blank SMEDDS formulation was acetic ether(as oil), RH40(as emulsifier), PEG400(as co-emulsifier).2. The ratio of suitable oils,emulsifier and co-emulsifier were screening by drawing the psedu ternary diagram. The best ratio of three things is acetic ether : RH40: PEG400=9:14:7. Blank SMEDDS was prepared according to best ratio, and add medicine . Investigate candesartan cilexetile SMEDDS particle size and shape. After being diluted with water for 100 times, candesartan cilexetile SMEDDS consisted of small spherical drops with the mean size of 3.6 nm. Detect SMEDDS of candesartan cilexetile , it contained 10.5mg·mL-1. The candesartan cilexetile SMEDDS was a translucent and achromatous solution with good stability.3.Candesartan cilexetile SMEDDS capsule were prepared by some technology. SMEDDS capsule were compared its vitro dissolution in three mediators with tablets. And the dissolution release of SMEDDS capsule was not influnced by different dissolution medium.the rate of SMEDDS capsule was much fast than tablet.4. Pharmacokinetics in vivo of rats: the candesartan cilexetile exists metabolic product candesartan in blood. HPLC method was built to measure the contents of candesartan. By lavaging rats with the suspension of candesartan cilexetile tablets , SMEDDS of candesartan cilexetile these AUC were measured. Experiment in vivo show that candesartan cilexetile SMEDDS solution, candesartan cilexetile tablet has the Tmax Cmax AUC of 3.5,4.5 h;90.68, 74μg/L ;935.005, 377.817μg/L*h.In this paper, According to the research in vitro and vivo, Candesartan cilexetile self-microemulsion enhanced absorption,dosage-carried of candesartan cilexetile is improved highly, its small drop improved solubility in vivo and bioavailability.