Preparation And Quality Evaluation Of Nanosizing Glibenclamide Tablets

Glibenclamide belongs to the second generationg sulfonylurea oral medications,it can regulate pancreatic beta cells,make insulin early release,improve the surrounding tissues to insulin sensitivity,and improve their ability to the absorption of insulin and reduce glycogen output.Glibenclamide belongs to the Biopharmaceutics Classification System class II drug,the absorption and bioavailability of glibenclamide are influenced or limited due to the poor solubility of drug.In this parper,glibenclamide nanocrystal was preparated using nanocrystal technology,and then made the glibenclamide nanocrystal tablets,with the expectation of increasing the solubility and dissolution,and improving the drug absorption and bioavailability via reducing particle size of the drug.The UV and HPLC methods were established respectively in this paper for the analysis of the dissolution rate and the assay of glibenclamide.The results showed that the methods were accurate,reliable,stable.In this paper,high pressure homogenization method was employed to prepare glibenclamide nanocrystals,and the technological conditions of this method were also studied with particle size and PDI as evaluation index.The process parameters,such as drug concentration,type and concentration of stabilizer,the pressure of high-pressur homogenizer,homogenization circle number were investigated respectively via single factor tests.On this basis,the process conditions were optimized in an orthogonal experiment of four factors and three levels.And the results indicated that the optimized process parameters were as follows: the concentration of stabilizer PVPK30 was40%(relative to the drug amount),the concentration of drug was 10 mg/m L,the circulating pressure was 1200 bar,and the circle index was 11 times.In this paper,the pharmaceutical characteristics of glibenclamide nanocrystals were studied,such as particle size,appearance morphology,crystalline state,solubility and dissolution rate,etc.The results indicated that the appearance of self-made nanocrystals was irregularly cube particles,the particle mean diameter was 515.2 nm with uniform particle size,and the chemical structure and crystalline state of glibenclamide nanocrystals weren’t changed obviously.The solubility and dissolution of glibenclamide nanocrystals have a certain increase.In this perpar,the influences of disintegrating agent,filler and lubricant on properties of nanosizing glibenclamide tablets was investigated respectively.The optimized prescription ingredients of the tablets were as follows: the amount of glibenclamide nanocrystals was equivalent to 2.5 mg glibenclamide,and MCC,PVPP,talcum powder was 74.5%,5.0%,1.5%,0.3% of total amount.The nanosizing glibenclamide tablets were of smooth appearance,uniform color,and suitable hardness,breakage,disintegration of the tablets were all meet the Chinese Pharmacopoeia 2015 edition requirements.The content was uniform,quality was stable among batches.In addition,the dissolution was obviously increased with a good reproducibility.The wistar rats were selected as experimental animals and the HPLC method was established to determine plasma concentration of glibenclamide in the study.Pharmacokinetics of the self-made tablet were studied by single dose tests with physical mixture and commercially available tablet as contorl.The study results were as follows:the drug absorption and bioavailability of self-made tablet was improved,and the relative bioavailability were 425.89% and 178.04% compare with physical mixture and Commercially available tablet,respectively.