Study On Oleanolic Acid Sustained-release Tablets

Oleanolic Acid (OA) is pentacyclic triterpenoid compound, which is mainly applied to protect and detoxify liver, lower grease and blood sugar, and cure certain disease of immune system. In clinical applications, for curing icteric hepatitis or chronic active hepatitis, the preparations of OA are made as tablets and capsules. And according to icteric hepatitis or chronic hepatitis, they generally need to be taken three or four times respectively. Compared to such applied preparations, the sustained-release tablets have obvious advantages: decreasing the frequency and the dosage, keeping steady serum concentration, reducing the side effects and adding clinical preparations, therefore, it has an extensive prospect for clinical applications in the near futureIn this article, we mainly studied several characteristics of OA sustained-release tablets, including formulation and design, quality standard, the influence factors for the in vitro dissolution and stability experiment.Selected the formulation of the OA sustained-release tablets by orthogonal design, and took HPMC as main complement, starch and lactose as additives. Then according to assaying its release-rate, observed each complement's effects on the sustained-release capability. By literature and the results of this experiment, the main factors that influence the quality of sustained-release OA included: the dosage and the viscidity of the HPMC, and the proportion of starch and lactose. Eventually, the optimized prescription of the sustained-release OA was: HPMC (K4M) as hydrophilic gel matrices material; 30% dosage; 1:1 starch and lactose.Based on the optimized prescription, we studied various factors(such as adhesives,moistening agents,dissolution media,compaction pressures,pH,rotational speeds and so on)affected the in vitro dissolution. The technique of amplified production was equivalent incremental classification sift. The dissolution medium was 0.5%SDS (PH=7.00±0.05); the rotational speed was 100rpm; and the dissolution method was rotating basket.According to the related requirements of the appendices of Chinese pharmacopoeia (2000 edition,Ⅱpart), a quality analysis of the OA sustained-release tablets, including their characters, identification, inspection, quantification, etc, was made. By the groping chromatography condition and studying of methodology, HPLC method was able to determine the contents of the sample precisely, thus was selected to make quantification. Eventually, the quality standard of OA sustained-release tablets had been established. Quality inspection to the three blocks of medium amplified preparations was made according to the standards, and their results satisfied the related regulate. Meanwhile the release of OA sustained-release tablets in vitro fitted the Higuich equation. The 12h accumulating releasing rate was above 90%, which indicated such tablets have desirable sustain-release capability.We investigated the stability of the three blocks medium amplified preparations, including stress testing (illumination,high temperature and high moisture),accelerated testing,long-term testing. The results of stress testing showed that the sustained-release tablets are stable under illumination,high temperature and high moisture (the release rate increased). Therefore, we selected the packing materials under high moisture. The rest two tests also showed that the sustained-release tablets keep stability.