Preparation And Evaluation Of Sustainedrelease Tablet Of Glipizade Based On Microenvironmental PH Modulation

Presently,tew researches were reported in application of the technique,microenvironmental pH modulation,to the pharmaceutics for poorly soluble drug.Its advantages of low cost,simple manufacture process,and little requirement in fabrication facilities,make it has promising prospect in pharmaceutical industry.The methods of differential scanning calorimetry(DSC),Fourier transform infrared spectrometry(FT-IR)and HPLC were employed to analyze the compatibility among glipizide,excipients and pH modifiers in this paper.In the curves of DSC,the peak of glipizide was at about 208 ?,and affected by addition of lactose,magnesium stearate,and candidate pH modifiers.In the infrared spectrum,no alteration occurred in the characteristic bands of mixture and glipizide.The results of HPLC analysis showed that the content of glipizide and relative compounds had no change.All the evidence mentioned above proved that glipizide was compatible with excipients and pH modifiers.Inclusion complex of glipizide was produced and evaluated,and prepared into sustained tablet which was based on the technique of microenvironmental pH modulation,with HPMC and pH modifiers.The factors which had influence on the drug release,including the viscosity of HPMC,the sort and amount of fillers,pH modifiers were investigated.The amount of HPMC K4M,HPMC K100LV,lactose,MgO and dicalcium phosphate anhydrous was chosen as variance to optimize the formulation with D-optimal mixture design.The cumulative drug release in 2 h,8 h,24 h and similarity factor(f2)were as responses.The results demonstrated that the drug release behaviors of optimum formulation in pH 6.8 and pH 1.2 dissolution medium were similar with the f2=73.0,which meant that the release profile of glipizide was pH-independent.The drug release data of selected three formulations was fitted in different model.The drug release behavior of three formulation was fitted in Higuchi model,which demonstrated that drug release mechanism was controlled dominantly by Fickian diffusion with auxiliary matrix erosion.The microenvironmental pH in the tablet core was assayed by pH indicator method,besides,the hydration and erosion behavior of the tablet was determined by gravimetry.The property of the gel layer was assayed by texture analyzer.The cause of influence the drug release and its hydration and erosion behavior was induced by the difference of strength and solubility of the pH modifiers.The analytical method of LC-MS/MS was applied to investigate the pharmacokinetics and in vitro and in vivo correlation in beagle dog of self-made glipizide sustained tablet.The drug plasma concentration in six healthy beagle dog was assayed.The results elucidated that the Cmax was 945.52±244.45(ng/mL),Tmax was 3.67±0.82(h),AUC0.36 was 4773.59±1198.14(ng ·h/mL).The result of one-way analysis of variance displayed that no difference was found between individual and group.The result of Wagner-Nelson method analyzing the in vitro-in vivo correction of the tablet showed that,the tablet release slowly in beagle dog,and had good in vitro-in vivo correlation.