Development of a Discriminative and Biorelevant Dissolution Test Method for Atorvastatin/Fenofibrate Combination with Appliance of Derivative Spectrophotometry.

OBJECTIVES

Nowadays, the market is flooded with combinations of drugs in various dosage forms, but there is a lack of official methods to quantify them. A single dissolution test method for the analysis of combined dosage form is preferred for simplification of quality control testing.

MATERIALS AND METHODS

If the developed dissolution medium mimics the biorelevant and discriminating dissolution procedure for drug products with limited drug aqueous solubility it is a useful tool for qualitative forecasting of the behavior of formulations.

RESULTS

Dissolution profiles were evaluated for atorvastatin and fenofibrate in capsules, using a paddle-type United States Pharmacopeia dissolution apparatus in 900 mL of medium at 50 rpm and 37±0.5°C. The best medium was 900 mL of 0.5% w/v sodium lauryl sulfate. The cumulative % dissolution was more than 85% within 45 min for marketed tablets. The proposed dissolution test conditions have discriminative power, dissimilarity factor (f) values are low (12-16%), and similarity (f) factor values are also low (45-48%). Hence the use of 0.5% w/v sodium lauryl sulfate solution is justified.

CONCLUSION

The dissolution method was validated (% relative standard deviation <2). To quantify both drugs simultaneously, a second derivative spectrophotometric method was established (λ 281 nm and 296 nm, respectively, for atorvastatin and fenofibrate) in acetate buffer, pH 2.8 solution.