Study On The Preparation Process Of Empagliflozin Metformin Tablets

Empagliflozin metformin tablets(trade name Synjardy)is a compound preparation of empagliliflozin and metformin hydrochloride.It was co-developed by Boehringer Ingelheim-Lilly and was first approved in EU in June,2015.Clinically it was used for the treatment of adult patients with type 2 diabetes mellitus(T2DM),and was approved for marketing in the United States in August of the same year.In February 2019,Synjardy was approved by NMPA for listing in China.The approved indication is to better control blood glucose combined with exercise and diet in adult patients with T2 DM.As a new drug product,it has a very good market prospect.So,this paper focused on the preparation technology research of empagliflozin metformin tablets.The research includes:(1)Methodology Reaearch on Empagliflozin Metformin TabletsIn this paper,HPLC method was used to determine the content,dissolution and related substances of empagliflozin metformin tablets.Then this article carried out the validation of analytical methods,including the verification of content determination,dissolution rate determination and related substances determination.In order to verify the reliability and accuracy of the analytical method,it is usually necessary to investigate the system suitability,precision,repeatability,sample solution stability,linear range,and sample recovery rate of the analytical method.The results show that the method is specific,sensitive,accurate and controllable.(2)Prescription Study of Empagliflozin Metformin TabletsBased on prescription of RLD and properties of Empagliflozin & Metformin Hydrochloride,the fluidized bed was adopted for granulation process,following by tableting process.Afterwards,considering the domestic wage ofexcipients,compatibility test of API & excipients were conducted to determine the proper excipients.Among the excipients,microcrystalline cellulose p H101 is used as filler,polyvinylpyrrolidone va64 as binder,The colloidal silica acts as glidant while magnesium stearate is selected as lubricant.The single factor test was used to select and optimize the dosage of the preparation,ie,Empagliflozin Metformin Tablets.Take the indexes of particle fluidity,friability,angle of repose,Karl's coefficient,hardness,tablet appearance,disintegration time and dissolution curve as indicators,The prescription contains 5mg empagliflozin,500 mg metformin,30.1mg microcrystalline cellulose p H101,47.2mg polyvinylpyrrolidone va64,4.2mg colloidal silicon dioxide,and 3.6mg magnesium stearate was finalized.(3)Process Study of Empagliflozin Metformin TabletsEmpagliflozin Metformin Tablets were prepared using the fluidized bed granulation,formability by tableting process.The fluidity of the intermediate particles,tablet formability,dissolution curve,disintegration time were used as the main inspection indicators.Single factor test was used to optimize the preparation process.Parameters as intermediate particles,tablet hardness,coating weight gain,raw material particle size were optimized during the study.The development of the production process of Empagliflozin metformin tablets,from laboratory-scale to industrial-scale batch was achieved,Through analytical research,the results of product appearance,weight difference,assay and dissolution showed that all the experimental batches of products were consistent with the original products in vitro.(4)Study on the Stability of Empagliflozin Metformin TabletsIn accordance with the “Technical Guiding Principles for the Stability Research of Chemical Drugs(APIs and Preparations)”,using samples of pilot scale(100,000tablets),the influence(light,high temperature,high humidity)on table stablity were investigated under acceleration test and long-term test conditions.The experimental results show that the appearance,content,related substances,dissolution rate and other indicators of this product have not changed significantly during the experiment,which proves that the product has good stability.The results show that the preparation of Empagliflozin Metformin Tablets is reasonably designed,The work showed the feasibility of preparation process,good product stability,consistency with the quality of the original product,and therefore,it can replace the original product.Our research work has important theoretical guidance significance and high practical application value.