Development Of Mirabelong Sustained-release Tablets

Objective:To establish the quality control method of Mirabegron sustained-release tablets by the research of the prescription process,the optimal prescription and preparation process and to provide experimental basis for new drug development by conducting A comprehensive comparative study on pharmaceutical quality of the original products in in vitro.Methods:The HPLC method was used to establish a method for determining the content of Mirabegron,related substances and antioxidants in Mirabegron sustained-release tablets.On the basis of the analysis of the original formulation,the composition of the formulation was preliminarily determined through the compatibility test,the study of the crystal form and solubility test.Taking the release as the main inspection index,the formulation and preparation process parameters of Mirabegron sustained-release tablets was optimized by the single factor method.Taking the release,related substances,and content as the main indicators,were used to establish the quality control method of Mirabegron sustained-release tablets was established by UV and HPLC methods.the f2 factor was used to evaluate the release curves of self-developed and original Mirabegron sustained-release tablets in different release media.Results:1.The chromatographic conditions of Mirabegron in Mirabegron Sustained-Release tablets:Agela C18(4.6×250mm,5?m)chromatographic column,mobile phase:0.01mol/L dipotassium hydrogen phosphate(the pH was adjusted to 5.0 by phosphoric acid)-acetonitrile=72:28,detection wavelength:248nm,flow rate 1.0ml/min,injection volume:10?l.The chromatographic conditions of related substance:Agilent 1100 high performance liquid chromatograph(equipped with DAD detector),chromatographic column:Waters Xbridge C18(150×4.6mm,3.5?m),with 0.01mol/L dipotassium hydrogen phosphate solution(pH was adjusted to 5.0 by phosphoric acid)as mobile phase A,and acetonitrile as mobile phase B for gradient elution.Detection wavelength:250 nm.The chromatographic conditions of antioxidant content:octadecylsilane bonded silica as filler;mobile phase is methanol-water(92:8),pH was adjusted to 3.0 with phosphoric acid,detection wavelength is 280 nm.2.The best prescription composition of Mirabegron sustained-release tablets:Mirabegron 50mg,polyoxyethylene 2000000 70mg,polyethylene glycol 8000 119.6mg,butylated hydroxytoluene 0.4mg,hydroxypropyl cellulose 7.5mg,stearin Magnesium acid 2.5mg,compressed by fluidized bed process.3.Release conditions of Mirabegron sustained-release tablets:phosphate buffer(pH=6.8)as release medium,volume 900 ml,basket method,rotating speed 100 r·min-1,temperature 37±0.5?.The release test results of the three batches of samples are 201805004 batch:1h,8.2%;3h,32.1%;8h,94.7%.201805005 batch:1h,9.4%;3h,35.5%;8h,91.6%.201805006 batch:1h,9.3%;3h,34.8%;8h,92.8%.4.The similar factors of Mirabegron sustained-release tablets and the original formulation under the four main media are 0.1M hydrochloric acid:70,pH 4.5 buffer:61,pH 6.8 buffer:75,water:69.Conclusion:The formulation and preparation process of the Mirabegron Sustained-Release tablets selected in this study are reasonable and feasible.The Mirabegron Sustained-Release tablets developed are similar to the original preparations in vitro release.The proposed quality control method is specific and reproducible and can effectively control the quality of Mirabegron sustained-release tablets.