| Objective:To study the preparation and quality of amlodipine and valsartan and hydrochlorothiazide tablets.Methods:1)Selected hydroxypropyl methyl cellulose ethanol solution of different concentrations as adhesion agent of wet granulation,study the result of the granulation and dissolution.Moreover selected dry granulation process for the preparation of amlodipine and valsartan and hydrochlorothiazide tablet. Study the flow agent and disintegrating agent dosage with single factor method. Compare the self-made preparation with the reference preparation in vitro bioavailability using f2factor method.2)Study the pilot production and process validation of amlodipine and valsartan and hydrochlorothiazide tablet.First mix amlodipine, hydrochlorothiazide, colloidal silicon dioxide and magnesium stearate for20minutes,then add other inactive ingredients and valsartan, mix for another20minutes.Granulate the mixed powder above with dry granulator,then add magnesium stearate and compress,200tablet per minute.Coat the tablet with high performance coating machine,control the temperature of tablet at30℃.Pack the film coated tablet using aluminum-plastic packaging machine.Take samples at each process of pilot production,do process validation.3)Study the quality of amlodipine and valsartan and hydrochlorothiazide tablet, determined the detection wavelength of three active components,established the HPLC method to examine the content and dissolution of amlodipine and valsartan and hydrochlorothiazide tablet.Tested and verified the HPLC method,investigated the linearity, recovery,stablity of solution repeatability and intermediate precision.Determined the content and dissolution of the three batches of amlodipine and valsartan and hydrochlorothiazide tabletResults:1) Selected dry granulation as the prodution process of amlodipine and valsartan and hydrochlorothiazide tablet,The proportion of magnesium stearate in granule formulation is1.5%and magnesium stearate mixed with granule is1%.The proportion of colloidal silicon dioxide is2.5%,and the proportion of crospovidone is8%.The dissolution curve of self-made preparation and reference preparation in water,pH4.5and pH6.8phosphate buffer were similar,and was not similar in pH1.0Hydrochloric acid solution.2) The results of process validation demostrate that the contentof the samples got from different position of the mixing machine were all between95%-105%,the content of the tablets sampled were all between90%-110%(A+1.80S≤15.0).The tablet weights were between95%-105%of the theoretical weight.The hardness of the samples were all above3.5kg/mm2.The friabilities were below1%.3) A HPLC method was established for determination of the content of each active component.According to the ultraviolet spectrum of the three ingredients,the detection wavelength of each component is determined, amlodipine and valsartan at237nm, hydrochlorothiazide at272nm.The standard curve of Amlodipine was linear in the range of14.1～42.3ug· ml-1, and the correlation coefficient was0.9999. The standard curve of valsartan was linear in the range of16.1～48.3ug·ml-1and the correlation coefficient was1. The standard curve of hydrochlorothiazide was linear in the range of12.6-37.8ug· ml-and the correlation coefficient was1. The resolution of Hydrochlorothiazide, valsartan, amlodipine and blank inactive ingredients is acceptable.The HPLC method was accurate,efficacy and with strong specificity. A HPLC method was established for determination of the dissolution of each active component.Besides using the same HPLC condition,900mL of pH6.8phosphate buffer was chosen as the dissolution medium of amlodipine and valsartan and hydrochlorothiazide tablet,the rotational speed of dissolution tester was50r/min, Sampling time was30min,the dissolution of each active component must be above ninety percent.The standard curve of amlodipine was linear in the range of3.94-11.82ug· ml-1, and the correlation coefficient was0.9999. The standard curve of valsartan was linear in the range of108-252ug· ml-1, and the correlation coefficient was0.9999. The standard curve of hydrochlorothiazide was linear in the range of7.05～21.15ug· ml-1, and the correlation coefficient was1. The content and dissolution of three batches of amlodipine and valsartan and hydrochlorothiazide tablet met the requirements.Conclusion:Amlodipine and valsartan and hydrochlorothiazide tablet was equal to the reference preparation, the preparation method was simple and with strong repeatability and stability. The HPLC method for content and dissolution determination was accurate, reliable and well specified.The resolution between each active ingredient is great. The content and dissolution of the three batches of Amlodipine and valsartan and hydrochlorothiazide tablet met the requirments, which illustrate the the production method of amlodipine and valsartan and hydrochlorothiazide tablet was stable and effective from another perspective. |
