The Preparation And Quality Control Of Sitagliptin Phosphate Tablets

Objetive:Diabetes mellitus?DM?is a metabolic disorder characterized by chronic hyperglycemia.It can involve all systems of the body,include serious complications and endanger human health.More than 90%of them are type 2 diabetes mellitus?T2DM?.In recent years,with the aging of the population and the continuous improvement of people's living standards,the incidence of type 2 diabetes is increasing day by day,and the incidence of type 2 diabetes is also increasing rapidly.The World Life Organization predicts that in 2025,the number of diabetes patients will reach 300 million in the world.Traditional drugs for diabetes include sulfonylurea,glinide,biguanidine,thiazolidinedione,glucosidase inhibitors and insulin,all of which have varying degrees of adverse effects,such as weight gain,gastrointestinal reaction and hypoglycemia,so the development of new targets,no side effects of traditional hypoglycemic drugs,the protection of islet B cells of a new type of antidiabetic drugs is urgent.The main targets related to the pathogenesis of diabetes are glucagon-like peptide-1,dipeptidyl peptidase-4 and so on.At present,the main targets related to the pathogenesis of diabetes are:glucagon-1,dipeptidyl ptidase-4,dodium-glucosecotransporter-2,glycogensynthasekinase-3,protein tyrosine phosphatase,glucokinase and so on.Sitagliptin phosphate is a DPP-4inhibitor,which is glycemic dependent,moderate hypoglycemic,increases insulin secretion without hypoglycemia,effectively relieves hunger,effectively relieves hunger,and has no nausea and vomiting,Side effects such as edema and weight gain.At present,the domestic market has been imported preparations of sitagliptin phospate tablets?Januvia,Merck Sharp&Dohme?,but there is no generic drug.Central composite design-Response surface methodology was used to get the final optimal prescription of sitagliptin phosphate tablets.And accurate and reliable quality control method was established to control the quality of homemade preparation and its stabilitybyultravioletspectrophotometryandhighperformanceliquid chromatography.At the same time,the consistency of the self-made preparation was evaluated by using Januvia^?as a reference preparation.Methods:This trail is based on the production of Januvia^?by Merck Sharp&Dohme Pty Ltd,then the central composite design-response surface methodology and single factor method were applied to screen and optimize the best prescription.First of all,to determine the general composition of the prescription of sitagliptin phosphate by consulting relevant information of Januvia^?.then through the single factor investigation about understanding the variety and dosage of tablets prescription of some accessories,and united star design-response surface optimization method,comprehensively studying the effect of relevant factors on the tablets.Using the dispersible uniformity and 15 min cumulative dissolution as evaluation indexes,the central composite design-response surface methodology was employed to optimize the amount of materials.Simultaneously,as sitagliptin phosphate tablets to establish accurate and reliable method for quality control.Selects the UV and HPLC methods to tablet of homemade test.While referring to"Chemical stability study technical guidelines"and the characteristics of sitagliptin,the implementation of strong acid,strong alkali,strong oxidizing damage test,according to the influencing factors for the optimal prescription test,accelerated test and long-term test,for the study of the prescription design,process improvement,quality,packaging,transportation,storage,such as the provision of relevant information.Results:The final prescription was confirmed as the following.In the sitagliptin phosphate tablets,the compositions of sitagliptin phosphate are 64.4 mg,MCC,CaHPO₄·H₂O,CCNa and magnesium stearate were 161,50,96.6and 3.5mg.The method for quantitative determinations established by ultraviolet spectrophotometry and high performance liquid chromatography was accurate and reliable.Chromatographic conditions of sitagliptin phosphate is determined as:choosing reverse silica gel KromasilC18 chromatographic column?200mm×4.6mm,5?m?;velocity detection wavelength was set at 205 nm,the flow rate was set to0.8mL/min,column temperature was controlled at room temperature,and mobile phase is methanol:0.1%perchloric acid solution?45:55?.At the chromatographic conditions,sitagliptin phosphate in 6.4⁹6?g/mL within the scope of linear good,high accuracy and good precision.Results show that this method is accurate,specific,and can be used for content determination of the sample.The sitagliptin phosphate bulk drug and formulations were stable to strong acids and alkalis and unstable to strong oxidizing.The influencing factors results showed that:high temperature,high humidity conditions and light were all affecting the sitagliptin phosphate tablets.Therefore,suggesting that the tablets should be sealed packaging and stored in a cool and dry place.Long-term test has only conducted to 12months.In the meanwhile,various examining indexes of the preparations were meeting related requirements,showing basic stability.The expiration period was to be tested further to complete.Conclusion:The optimum preparation method of sitagliptin phosphate tablets was screened out in this experiment.The self-made sitagliptin phosphate tablets have excellent appearance and uniform content.Compared with the marketed tablets,the dissolution behavior of the tablets is significantly improved.The determined HPLC method has the advantages of good specificity and convenient use,and can be used for the determination of the content of sitagliptin phosphate.