Preparation Of Glibenclamide Sustained Release Tablets

Objective:To screen the optimalizing formula of extended action tablet of glibenclamide,and establish the assay method of the drug concentration in plasma.Methods:In this paper,the releasing degree in vitro was used as indicator to evaluate the effects of HPMC viscosity,diluents,cohesives and squash pressure on the extended action tablet of glibenclamide.HPMC was selected as hydrophilic gel matrix, lactose and ethylcellulose(EC) as the diluents,and 70%alcohol as cohesives.The prescription of extended action tablet of glibenclamide was excellently screened with L9(3⁴) orthogonal design,and three influencing factors such as HPMC,EC and lactose were selected.The levels of HPMC were 40,50,and 60mg;the level of EC 10, 20,and 30mg;the level of lactose 80,100 and 120mg,respectively.The releasing rate of each prescription in vitro was determined and analyzed so as to choose the best.Result:The releasing mechanism of sustained-release tablet was primarily studied. Several drug-releasing models were simulated and showed that the drug-releasing curve in vitro was consistent with Weibull equation LnLn(1/(1-F))=1.11761nt-1.8746 (r=0.9998).The release parameter n obtained from Ritger-Peppas equation was 0.7549,between 0.45 and 0.89,indicating that the release mechanism was diffusion as well as matrix erosion,which accords with retard tablets.High performance liquid chromatography(HPLC) method was developed to determine the releasing degree in vitro.The concentration of glibenclamide and AUC were linear over the range of 0.5μg.mL^-1～12μg.mL^-1,A=9948.3C+30.851 (r=0.9999).The mean absolute recoveries of low,middle and high concentrations were 100.2%,99.83%,99.70%.The inter-day RSD were 1.7%,1.4%,and 1.1%;and the intra-day RSD were 1.6%,1.3%,and 1.0%,The two kinds of RSD were both lower than 2%which showed this method was accurate,reliable and reproducible.HPLC method was established to determine the concentration of glibenclamide in plasma.The glibenclamide concentration had a good linear correlation in the range of 3-300ng·mL^-1 Y=0.0229X+0.0309(r=0.9999).The lowest detectable limit was 3ng·mL^-1.The mean absolute recoveries of low,middle and high concentrations were 70.84%,71.00%,and 74.41%.The method recovery rates were 96.23%,97.54%,and 95.47%;The inter-day RSD were 2.9%,3.2%,and 3.2%;and the intra-day RSD were 1.3%,2.6%,and 3.6%,The two kinds of RSD were both lower than 5%.Conclusion:This preparation prescription is reasonable,and the preparation technology is feasible.This assay method is sensitive,accurate,simple and feasible.