Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus

Abstract

Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37–57°C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.