Comparative study of the dissolution profiles of a commercial theophylline product after storage

Abstract

The purpose of this work was to study the effect of storage time and temperature on the in vitro release kinetics of a commercial sustained-release dosage form of theophylline, at different pHs of the dissolution medium. The formulation was stored at 35°C for 16 months and at 45°C for 8 months, with a relative humidity of 60%. The in vitro release tests were performed at pHs 2, 4, 6 and 7.4. The mean values of the transport coefficient n, were close to 0.5 in all the conditions tested, which indicates that the transport system is not modified after storage of the formulation at 35°C and 45°C. The mean values of the dissolution rate constant ranged from 0.036 to 0.043 min^-n, under all the conditions tested. Significant differences (α=0.05) were found between pHs 2, 4 and 6, 7.4 for all the model-independent parameters studied. When the formulation was kept at 35°C for 16 months, the mean percentage of drug dissolved at 8 hours was 25.61% (pHs 2, 4) and, 36.12% (pHs 6, 7.4), representing a 26% and 24% reduction, respectively. Similar results were obtained after storing the formulation at 45°C for 8 months, corresponding to 33.3% (pHs 2, 4) and, 22.5% (pHs 6, 7.4) diminution, respectively.The values of the similarity factor, f₂, obtained were lower than 50, which indicates the lack of similarity among the dissolution profiles, after storing the formulation under the experimental conditions tested.