In-vitro Study and In-vivo Predictions of Valsartan and Amlodipine Capsules through Micro Tablets

Abstract

Aim: The present research work was carried out to develop Valsartan and Amlodipine capsules using micro tablets and to evaluate the in-vitro drug release characteristics. The study was targeted to determine the systemic concentrations using in-vivo prediction. Study Design: The in vivo parameters along with the marketed Valsartan and Amlodipine product was predicted using WinNonlin® software external prediction method. Place and Duration of the Study: The present work was carried out at Pacific Academy of Higher Education and Research University, Udaipur between the duration of February-2019 to November-2019. Methodology: The dissolution studies were performed for test and reference products in 900ml Phosphate buffer (pH 6.8), and the USP Type II apparatus at 50 RPM with a sinker. The in vivo pharmacokinetic prediction was performed using WinNonlin® Software. A mechanistic oral absorption model was built in Phoenix® WinNonlin® 8.2 software (Certara, Princeton, NJ, 08540, USA). Results: The in-vitro dissolution studies were comparable between the test product and the reference product. The Similarity factor achieved was 61.7 and 84.8 for Amlodipine and Valsartan test product in comparison with the reference product. An average percent prediction error for Cmax and AUC for both Valsartan and Amlodipine achieved was less than 10% for all IVIVC models. Conclusion: The relatively low prediction errors for Cmax and AUC observed strongly suggest that the Valsartan and Amlodipine IVIVC models are valid. The average percent prediction error of less than 10% indicates that the correlation is predictive and allows the associated dissolution data to be used as a surrogate for bioavailability studies.