Research And Development Of Metformin Hydrochloride Sustained Release Tablets

Objective:To develop a chemical generic pharmaceutical metformin hydrochloride sustained release tablets,investigate the in vitro release of self-made and reference preparations,conduct human bioequivalence tests,and evaluate the consistency of self-made and reference preparations.Methods:1.Through preliminary analysis of the literature data of the original research product(trade name:Glucophage XR),preliminary determination of formulation prescription and process design of the original research product;preparation of biphasic hydrophilic gel using high shear granulation process with reference to the original research formulation formulation The skeleton granules and tablets are self-manufactured;2.The release rate is taken as the evaluation index,and the in vitro release behaviors of the self-products and the original research products are evaluated according to the determination method of the release degree in the import drug registration standards;3.The prescription screening and the technical durability Investigations,small-scale experiments,etc.,to determine the in vitro release of the small test formulation and process parameters consistent with the original study;4.Based on the small test prescription and process,using the pilot test equipment consistent with the principle of small-scale test equipment,conduct pilot test Study,verify the range of process parameters,produce 3 batches of samples,and conduct quality comparison study with the original research;5.Adopt single-dose,double-crossing,double-cycle test design method,take a batch of pilot samples and the original research products for bioequivalence test.Results:1.The best preparation prescription(1000 tablets)was metformin hydrochloride 500.0 g,microcrystalline cellulose 60.0 g,hypromellose K4M 150.0 g,hypromellose K100 150.0 g,sodium carboxymethyl cellulose.150.0g and magnesium stearate 10.0g,consistent with the original product;2.Small-scale trial process:mixing 5min and 10min average content of 100.1%and 100.0%,respectively,RSD values of 0.42%and 0.25%,65%ethanol solution During the preparation,the stirring speed is 400rpm,the shearing speed is l000rpm,the granulation is 1min,the nylon mesh is passed through 18 mesh,the moisture content in the whole grain process is controlled below 4%,and the average contents of the total mixed 5min and 10min are 100.2%and 100.1%,respectively,and the RSD values are respectively 0.14%and 0.21%,tableting process control pressure:130-180N,weight difference between±3%;4.The indicators of the pilot-scale self-product formulation meet the requirements,3 batches of homemade products release curve similar to the original research product.5.The in vitro consistency assessment showed that the release curves of the self-prepared products in different media were similar to those of the original study f2,which were 90,94,87,and 83,respectively.The bioequivalence results showed that The original product reached bioequivalence,and the 90%confidence interval for postprandial and fasting was between 80%and 125%.Conclusion:The self-preparation formulation is reasonable;the production process has good reproducibility and stability;the quality of the self-manufactured product produced is controllable and meets the metformin hydrochloride sustained-release tablet quality standard;the self-manufactured product has the same appearance as the original product and has the same in vitro release characteristics.Self-products and original products are bioequivalent.