Gliclazide Mr

Gliclazide (GZ) is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus (NIDDM or type-2 diabetes).It stimulates the secretion of insulin but doesn't increase the synthesis of insulin in the pancreas. It is effective for those patients who have the function of insulin secretion internally. To reduce the side effects and maintain relatively constant plasma concentration, a sustained released tablet of once daily administration was designed and prepared by using hydroxypropylmethylcellulose(HPMC) as basic matrix material.According to pharmacopeia, UV spectrophotomatry was developed for in vitro assay during the studies of physicochemical properties, content and release. In the preformulation researches the physicochemical properties of gliclazide were investigated, gliclazide solubilities in different solvent and stability. Octanol/water partition coefficient of gliclazide were investigated in different pH.On the basis of pharmaceutical preformulation studies, the effect of different formula composition, preparation procedure and dissolution condition on the drug release from the formulation was studied. Based on single-factor tests, the optimal formulation was obtained by 34 factors-analysis orthogonal. The release mechanism of gliclazide from tablets was also studied, and the result of which showed that the released mainly by with erosion combined diffusion from HPMC matrix in the first stage and mainly by tablet erosion during the later period.To make insoluble drug into sustained release tablets with simple and effective methods, in the paper a new kind of sustained release tablets with hydropropyl-β-cyclodextrin (HP-β-CD) as complex material was designed. Here, gliclazide was as the model drug again. Inclusion complexes of GZ with HP-β-CD were formed by the Freeze-dried method. Inclusion complexes formation was verified by differential scanning calorimetry (DSC) and infrared spectroscopy. The phase-solubility experiment was performed by the method reported by Higuchi and Connors. The phase-solubility profiles indicated that the inclusion complexes were formed at 1:1 molar ration of drug and HP-β-CD and the phase-solubility profiles belong to class-AL diagrams. The solubility of gliclazide was increased from 42.5μg/ml to 289.4μg/ml. To reduce the side effects and maintain relatively constant plasma concentration, a sustained released tablet of once daily administration was designed and prepared by using hydroxypropylmethylcellulose (HPMC) as basic matrix material.With single dose crossover design, the pharmacokinetics of GZ self-made sustained release tablets in dogs was studied comparing with the commercial tablets. The results indicated that the concentration-time curves of GZ tablets fit in one-compartment model. Compared with commercial tablets'peak time, Tmax of self-made tablets was extended to 1 to 3 hours, the curve of plasma concentration versus time became more flat with a satisfactory sustained release result and the mean residence time (MRT) was prolonged. Besides, the comparative utilization degree of bioavailability in sustained release tablets. reference commercial tablets was about 102.4%, with a good correlation coefficient between in vivo and in vitro experiments.