Determination Of Mirabegron Release Tablets And Stability Studies

Mirabegron Release tablets is a potent and selectiveβ₃ receptor agonist developed by Japan’s Astellas Pharmaceuticals for the treatment of overactive bladder（OAB）in adults.Clinical applications at home and abroad show that Mirabegron Release tablets has lower adverse reactions and higher patient compliance.It is a new type of oral sustained-release drug with high efficiency and good tolerance.This product is a generic drug of oral solid sustained-release preparations.The research on its content and in vitro release is the focus of pharmaceutical research,and it is also an important basis for in vivo efficacy evaluation.Therefore,based on the preparation product of Mirabegron Release tablets 25mg developed by Shenzhen Main Luck Pharmaceuticals Inc.,this study researched and established an analytical method suitable for the determination of the content and release of this product.Prove the accuracy and controllability of the method;use the developed method to conduct a comparative study on the stability of mirabegron sustained-release tablets and the reference preparation to verify the consistency of the quality and stability of this product with the reference preparation,as provide a basis for ensuring product quality is stable,effective and safe.The chromatographic column for content determination is ECOSIL C₁₈（4.6 mm×250mm,5μm）;acetonitrile-0.1%perchloric acid solution（30:70）was used as the mobile phase;the detection wavelength was 248 nm;the column temperature was 30℃,and the flow rate was 1.0 m L/min.The filter membrane adsorption was investigated for the test solution.When 5 m L of the test solution was discarded,there was no filter membrane adsorption effect.The specificity,linear range,limit of detection and limit of quantification,accuracy,repeatability,solution stability and durability of the method were verified,and all indicators met the requirements.The method can be used for the content determination of this product.The release study was conducted according to the recommended release test method for Mirabegron Release tablets in the FDA dissolution database,using 900 m L of p H 6.8phosphate buffer as the release medium,the rotation speed was 100 r/min,and the sampling time point was 1 h,3 h,5 h,7 h,8.5 h,10 h,12 h.The method was investigated,and the results showed that the rotation speed and the volume of the dissolution medium were reasonable,and the sampling time points were selected as 1 h,3 h,5 h,7 h,and 8.5 h.In order to ensure the accuracy of the results and investigate the adsorption of the filter membrane,when 2 m L of the reference solution was discarded,there was no filter membrane adsorption effect.When using a 13 mm filter membrane for the test solution,discard 2 m L of the solution,and when using a 25 mm filter membrane,discard 4 m L of the solution,which can eliminate the adsorption effect of the filter membrane.The specificity and system applicability,detection limit and limit of quantification,linear range,precision,solution stability,durability and accuracy of the method were verified,and all indicators met the requirements.Three batches of self-developed products and three batches of reference preparations were tested for release rate,and the results were consistent.This method can be used for the release rate determination of this product.Stability study on Mirabegron Release tablets,including influencing factors test（light test:4500 lx±500 lx;high temperature test:60℃±2℃;high humidity test:humidity 90%±5%;temperature 25℃）,Accelerated test（temperature 40℃±2℃,relative humidity 75±5%）,long-term test（temperature 30℃±2℃,relative humidity 65%±5%）.The influence factor test of self-developed product and reference preparation shows that this product is not resistant to high temperature,and its properties and release degree will change significantly under high temperature conditions;light has little effect on it;the packaging material used can effectively isolate water vapor.In the accelerated test and long-term test,all inspection items meet the requirements,and the shelf life of this product can reach 18months.In the stability test,the self-developed product and the reference preparation maintained similar changes,and the results were consistent.To sum up,the content determination method and release rate determination method adopted can be used for the quality control of this product,and the shelf life of this product can reach 18 months,which can provide a guarantee for the safety of clinical medication.