Predicting Dissolution of Entecavir Using the Noyes Whitney Equation

Abstract

The dissolution rate of a drug directly affects its absorption and utilization in vivo. The dissolution test is used to evaluate the quality of formulation and production process. Entecavir is approved by the United States FDA for the treatment of chronic hepatitis B. Entecavir monohydrate (ETV-H) is used in commercial ETV tablets. The anhydrous form of entecavir (ETV-A) often appears as an impurity polymorph during the preparation process. This study aims to investigate the dissolution behavior of ETV-H in four dissolution media (water, pH 1.2, pH 4.0, and pH 6.8) and compare with those of ETV-A. The dissolution rates of ETV-H at pH 6.8, pH 4.0, and ultrapure water were faster than those of ETV-A, resulting in faster complete dissolution of ETV-H. To save time in the dissolution testing, an analytical method based on the Noyes Whitney equation is proposed to obtain the fitted (predicted) dissolution curve. Differences (loss values) between the predicted and experimental dissolution curves for ETV-H at pH 6.8 and pH 1.2 were 0.0013 and 0.016, respectively. The proposed analytical method can save up to 75% of experimental time and can be used for dissolution testing of active pharmaceutical ingredients in the production of pharmaceutical crystals.