In vitro evaluation of mesalazine enteric-coated tablet dissolution by the reciprocating cylinder method

Abstract

Abstract Mesalazine formulations are first-line treatments for ulcerative colitis. However, the drug release mechanisms of currently available mesalazine formulations on the market vary, and different in vitro dissolution methods have been used to characterize their in vivo absorption. Thus, there is an urgent need for more in-depth research on in vitro dissolution methods for mainstream mesalazine enteric-coated tablets. The goal of this study is to determine more scientifically rigorous testing methods to enhance the discriminatory power of in vitro dissolution testing of these products. Dissolution tests were performed using the reciprocating cylinder method with a small 250 ml vessel, a reciprocating frequency of 10 cycles/min, a sample volume of 5 ml, and UV spectrophotometric detection. The absorbance values of the dissolution solutions at different pH values were measured using cuvettes with path lengths of 1 cm and 1 mm and at detection wavelengths of 303 nm and 332 nm, respectively. In pH 1.2, 4.5, 5.5, and 6.0 solutions, the linear concentration range was from 5 to 30 µg/ml. In contrast, the linear concentration range in pH 6.8 media was 90 to 660 µg/ml. Method accuracy was tested at levels of 5%, 50%, 100%, and 120%, and the average recovery rates were 105.8%, 102.8%, 100.9%, and 101.2%, respectively. Moreover, the differences in the dissolution data did not exceed 2% with different instruments or analysts or on different days. Using the reciprocating cylinder method, we continuously measured the dissolution of mesalazine enteric-coated tablets in media with various pH values that simulate different sections of the human digestive system. Furthermore, in pH 6.8 dissolution media, drug release from both the homemade and the reference formulations followed zero-order kinetics. The established reciprocating cylinder method for determining the dissolution of mesalazine enteric-coated tablets is suitable for quality control of this type of product.

Keywords

• Mesalazine enteric-coated tablets
• Reciprocating cylinder method
• Dissolution in vitro
• Methodology development and validation