On-line monitoring and simultaneous acquisition of multiple dissolution curves of pharmaceutical associations employing a chemometrics methodology

CALVO, N. L.; MAGGIO, R. M.; KAUFMAN, T. S.

C.A,B.A

Workshop; Biowaivers 2015; 2015

Evaluation of drug dissolution in dissolution tests is generally performed by UV-VIS spectroscopy or HPLC. However UV-VIS is a non-selective method and HPLC requires organic solvents and skilled labor.We have developed and validated an alternative methodology to simultaneously construct multiple in vitro dissolution curves by coupling on-line UV-Vis spectrophotometry to Multivariate Curve Resolution with Alternating Least Squares (MCR-ALS), employing amlodipine, valsartan and hydrochlorothiazide as model drug association.MATERIALS AND METHODSThe dissolution tests were performed in a dissolution test-station (USP apparatus II, phosphate buffer, pH 6.8, 37ºC). The dissolutions were continuously monitored using a UV-VIS spectrophotometer (range= 280-440 nm) and a peristaltic pump (1.5 ml/min).Five calibration standard solutions of amlodipine, valsartan and hydrochlorothiazide (1.3-13.3, 1.4-14.9 and 16-192 mg/l, respectively) were independently prepared and measured.RESULTSThe calibration and dissolution spectra were arranged matrixwise. Spectral and concentration profiles of the dissolution data were obtained with MCR-ALS, constrained for unimodality, non-negativity and selectivity.The analytes? concentrations in the dissolution curves were determined with calibration curves prepared by linear regressions of the calibration standards data. These results were statistically similar to those obtained by HPLC. The spectra of the analytes were also in good agreement with those provided by MCR-ALS, ensuring method selectivity.Method accuracy and precision were evaluated by a simulated dissolution experiment. The calculated and actual concentrations concentrations were not statistically different, with RSD values ≤ 2%.CONCLUSIONSThe coupling of UV-Vis spectroscopy and MCR-ALS can be advantageously exploited to simultaneously acquire the dissolution curves of all the active ingredients of multicomponent formulations.