Comparative in vitro dissolution and in vivo bioavailability of commercial amlodipine tablets
Purpose: To evaluate the in vivo and in vitro behavior of amlodipine immediate release products.
Methods: Three Mexican amlodipine products and the innovator (Norvasc®) were evaluated. Three bioequivalence studies were performed in 24 healthy male and female volunteers each. Plasma concentrations were determined using a liquid chromatographic method coupled with tandem mass spectrometry (LC/MS/MS). Dissolution profiles were evaluated using USP type apparatus 2 at 75 rpm and 500 mL of HCl 0.1N, pH 4.5 and pH 6.8. Also, the dissolution behavior of different lots of the innovator product was evaluated using apparatus 1 or 2 and 900 mL of buffer pH 6.8.
Results: All the generic products under study were bioequivalent to the innovator. In vitro data showed that although at pH 1.2 and 4.5, the products met the specifications for very rapidly dissolving products but at pH 6.8, neither the innovator nor the test products complied with the criteria for rapidly dissolving products. When the study was performed at pH 6.8 in 900 mL of medium, the innovator showed a rapid dissolution behavior.
Conclusion: The results show that the use of WHO conditions (900 mL of media, apparatus 2 at 75 rpm) are more adequate to predict the in vivo behavior of the amlodipine products.
Keywords: Biopharmaceutics Classification System (BCS), Dissolution, Bioequivalence, Solubility, Permeability