Development of Dissolution Test Method for Drotaverine Hydrochloride/Mefenamic Acid Combination Using Derivative Spectrophotometry

摘要

Purpose: To develop and validate a dissolution test method for tablets containing 80 mg of drotaverine hydrochloride (DRT) and 250 mg of mefenamic acid (MEF). Methods: Sink conditions, drug stability and specificity in different dissolution media were tested to optimize a dissolution test method using a USP paddle type dissolution test apparatus set at a speed of 50 rpm. The dissolution medium consisted of 900 ml of phosphate buffer (pH 6.8) containing 0.25% w/v cetrimide at 37 ± 0.5 oC and 45 min time-point. To determine both drugs simultaneously, a first derivative UV spectrophotometric method was developed and validated. Drug release was analyzed by first derivative UV method at 253.8 nm and 304 nm for DRT and MEF respectively. The dissolution method was validated as per ICH guidelines. Results: The two brands each showed 98% of drug release for both drugs when the developed dissolution method was used. The regression plot was linear in the concentration range 4 - 24 μg/mL for each of the drugs and regression coefficient (r2) was greater than 0.999 for each drug. Relative standard deviation (% RSD) for precision and accuracy of proposed method was Conclusion: The proposed dissolution method is simple, cost-effective, precise, accurate and specific. It can be successfully employed in routine quality control of DRT and MEF combination tablets.