Study On Ursolic Acid Sustained-release Tablet

Ursolic Acid (UA) is pentacyclic triterpenoid compound, which has wide resources. It has such functions as less poison, against tumour, against oxidate, against hepatitis, against ulcer and diabetes. It also has the functions of protecting liver and reducing hyperlipema. It has rich resource and can be a new medicine against tumour and hepatitis. It can also be used as the product for skin care. It has wide prospects for development. In recent years, the research of ursolic acid had obtained more important findings about basic studies, the methods of extraction and isolation for industry, advanced dosage forms and clinical uses.At present, the praeparatum of ursolic acid were reported on the itsβ-cyclodextrin inclusion compound which used in foods and the freeze injectable powder which as used a liver-target forming. Limited by the low bioavailability, the bioactivity of ursolic acid can not be fully shown up. Aiming to improving the therapeutic effect and safety, degrading the peak valley phenomenon of blood drug level, being simplify taking medicine, this experiment focous on researching the ursolic acid HPMC hydrophilicity gel matrix sustained-release tablets to increase the clinic preparations of UA.In this article, we mainly studied several characteristics of UA sustained-release tablets, including formulation and design, quality standard, the influence factors for the in vitro dissolution and its stability.Selected the formulation of the UA sustained-release tablets by orthogonal design, and took HPMC as main complement, starch and lactose as additives. Firstly investigate the influencing factors of delayed releasing function by preliminary experiments. By the results of this experiment, the main four factors that influence the quality of sustained-release UA included.The dosage of the HPMC, the variety of the binder, the proportion of starch and lactose and the hardness of tabletting. Eventually employ the L9(34)orthogonal table and the parameter of releasing degree to select the best formulation. The optimized prescription of the sustained-release UA was: HPMC (K4M) as hydrophilic gel matrices material; 20% dosage; 2:1 starch and lactose;tablet hardness 5kg/mm2.Based on the optimized prescription, we studied various factors(such as preparation technology,dissolution media,pH,the methods of dissolution determine,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 (2005 edition,Ⅱpart), we definited the feasible quality evaluation, established the quality standard. We checked up the items on the quality standard and investigated the stability of three batches of semi-works production. It lay foundation for a good preclinical research for the application of new drug and industry manufacture.The analysis of the UA sustained-release tablets including: characters, identification, inspection, quantification, etc. 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 UA 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 UA 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.The results of experiment showed all kinds of index of ursolic acid sustained-release tablets were ideal. It had satisfied delayed release performance in vitro release. Its release nature in vivo depended on a further experiment.