Development of a Sustainable Analytical Method Using High-Performance Liquid Chromatography (HPLC) and Dissolution Studies for Quality Control of Ibuprofen Soft Gelatin Capsules from Brazil.

Ibuprofen is one of the first anti-inflammatory drugs, and it has recently been developed in soft gelatin capsule form. Therefore, it is the only oral pharmaceutical for which there is no defined quality control method by pharmacopoeias. This study aims to develop an innovative and sustainable HPLC-DAD method for the determination of ibuprofen in soft gelatin capsules and to compare dissolution profiles and kinetics. The optimal conditions for the chromatographic method were a mobile phase (isocratic) consisting of 70% ethanol and 30% of 0.5% acetic acid at a flow rate of 0.8 mL min-1, a column temperature of 35 °C, a detector set to 220 nm, and a run time of 5 min. The metrics for assessing the method's sustainability were calculated based on the National Environmental Methods Index (NEMI) and the Analytical Greenness Metric (AGREE), yielding results of 2/4 and 0.72, respectively. Validation showed LOD and LOQ results of 0.7768 and 1.3673 mg L-1, respectively. Precision had a deviation below 5% and a working range of 1.37 to 20 mg L-1. No matrix effect was identified, and the method proved to be robust. The optimal dissolution conditions were defined through experimental planning as follows: 700 mL of phosphate buffer (pH = 7.2), 75 rpm, apparatus 2 (paddle), and 60 min of testing. The ibuprofen release percentage in the capsules ranged from 81.96 to 105.1%. Dissolution efficiency ranged from 32.17 to 45.97%. All samples exhibited first-order kinetics, with only three samples showing an F2 value above 50. No Brazilian studies were found that determined the presence of ibuprofen in soft gelatin capsules using high-performance liquid chromatography (HPLC), multivariate analyses, or expanded kinetic studies. Therefore, the developed method is innovative and more sustainable than others described in the literature according to the sustainability parameters. The method was validated for accuracy, LOD, LOQ, matrix effect, and robustness, ensuring effectiveness.