Formulation And Quality Evaluation Of KY43039 Tablets

[Objective]With the original formulation as a reference,the formulation and technology of KY43039 tablets were studied,KY43039 tablets were prepared,and the quality evaluation and preliminary stability investigation were conducted.Finally,a reasonable formulation technology of KY43039 tablets was obtained.[Methods]1.Investigate the quality characteristics of the reference preparation,conduct reverse engineering analysis of the reference preparation,investigate the particle size,crystal form and stability of the drug substance,and conduct the compatibility test of the raw materials and excipients;2.Through a single factor test,screen the amount and type of auxiliary materials(fillers,binders,disintegrants,lubricants),and finally get Appropriate models and dosages of various auxiliary materials,etc.3.The preparation process(wet granulation,fluidized bed granulation)is screened and related parameters are optimized,and finally a suitable preparation process is obtained.4.Take appearance,tablet weight difference,hardness,disintegration time limit,content uniformity,etc.as indicators to investigate its tableting process.And to investigate its coating process parameters.5.Using appearance properties,content,dissolution,and related substances as indicators,the preliminary stability of KY43039 tablets was investigated.[Results]The stability test results of KY43039 bulk drug showed that it was unstable to light,so it should be stored in the dark.The specification of KY43039 tablets was determined to be 40mg/tablet.Through single factor test,the prescription of KY43039 tablets was selected as:bulk drug 40g,lactose 100.4g,partially pregelatinized starch 100.4g,croscarmellose sodium 5g,6%hydroxypropyl cellulose,1.3g magnesium stearate,8.0g film coating premix,made into 1000 tablets,The granulation process is fluidized bed top spray granulation and tableting.The process is scaled up in three batches,the batch is 12000 tablets/batch,the process parameters of each key process are controllable,and the test results of the finished products are in compliance with the regulations.The dissolution behavior of the self-made tablets and the reference preparation is determined by the HPLC method.The dissolution rate in 4 kinds of dissolution media is more than 85%in 30 minutes,and the dissolution behavior of the self-made tablet is similar to that of the reference preparation.The influencing factors,accelerated test,and long-term test results of KY43039 tablets preliminarily show that KY43039 tablets packaged in aluminum-plastic blister are basically stable under the conditions of accelerated and long-term tests,and all index tests meet the requirements.[Conclusion]Research shows that the prescription of KY43039 tablets is scientific,and the preparation process is stable and feasible.Compared with the reference preparation,the quality characteristics,content,dissolution,and related substances are equivalent to the reference preparation.