Research Of Metformin Hydrochloride Enteric-coated Tablets

Metformin Hydrochloride(MH) is oral antihyperglycemic drugs used in themanagement of type2diabetes(noninsulin-dependent diabetes mellitus (NIDDM)).It is usedfor decreasing blood sugar levels both basal and postprandial plasma glucose. in people withtype2diabetes. The medication works in several ways:1. Improve insulin sensitivity byincreasing peripheral glucose uptake and utilization.2. Decrease hepatic glucose productionand output.3Increase the glucose utilization of non-insulin-dependent organization, such asthe brain, blood cells, renal medulla, intestinal, skin.4Inhibit biosynthesis and storage ofcholesterol, and reduce blood triglyceride, total cholesterol levels.5Inhibit glucose uptakeof intestinal cells. In this thesis, We have produced a better quality MH enteric-coated tabletswith a more affordable cost.Firstly,we have done the pharmaceutical preformulation studies, including theidentification of raw materials, establishment of analysis method of raw in vitro and theinspection of stability of raw materials. We developed HPLC method to determine thecontent of raw materials of MH for the analysis in vitro. Method validation was performed interms of sensitivity, repeatability, accuracy, and quantification limit, and the method issuitable for the analysis of MH raw materials in vitro. Stability study includes hightemperature test, illumination test and high humidity test, and the results showed that MHraw materials were stable to high temperature and illumination, while very hygroscopic, sowe need to pay attention on storage and transportation.We determined the prescription of MH enteric-coated tablets by prescription screening,and optimized the prescription on the process of preparing. Investigation mainly includesdiameter of sieve, the mixing time of the adhesive, drying temperatures of particle, watercontent in particle, mixing time after adding the lubricant and glidant, abletting pressure,different proportions increase in weight of isolated-coat and enteric-coat. As a result, we gotthe tablets with smooth surface, moderate hardness, and a high release rate by optimization prescription.The quality criteria of MH sustained-release tablets including character, identification,related substance, content and accumulated release was developed. The results of qualitystudies on self-prepared MH enteric-coated tablets showed the homogeneity of one batchand the repeatability of three batches were good. Three batches tablets complied with thestandard. Compared with marketed drugs on release and related substances, the resultsshowed that the increase in the isolated-coat did not affect the release of metforminhydrochloride, and can improve the stability of the drug during storage.Stress’ test, accelerated test and long-term test were carried out to investigate thestability of MH enteric-coated tablets. Character, content, related substance and accumulatedrelease were also studied. The results showed that light and temperature had little effect onsustained-release tablets, and under the conditions of80%relative humidity MH theenteric-coated tablets were still stable.