DETERMINATION AND APPLICATION OF BIORELEVANT DISSOLUTION MEDIA TO MEET THE IN-VIVO PERFORMANCE IN VALSARTAN AND CHLORTHALIDONE IN SOLID DOSAGE FORM

Dissolution testing with biorelevant media is used in the pharmaceutical industry as a predictive tool for the estimation of drug formulation’s in-vivo performance in bioequivalence studies. The objective of this study was to determine the biorelevant dissolution media enabling the prediction of in-vivo performance of Valsartan and Chlorthalidone in solid oral dosage form as new fixed drug combination. Dissolution profiles were performed in different pH medias for the evaluation of Valsartan/Chlorthalidone film-coated tablets. The validation studies of the used dissolution method were conducted by performing the parameters specified in the ICH (The International Conference on Harmonization) Q2 (R1) Guideline and the results met the acceptance criteria. Although in-vitro dissolution test findings showed the similarity of release profile of test and mono reference drug products, the in-vivo results demonstrated that they are not similar. For this reason, biorelevant media was investigated and defined. This media proved to be biorelevant and has the potential to be further used to establish in-vitro in-vivo correlation (IVIVC) during the development of Valsartan and Chlorthalidone in solid dosage form.