Development and validation of dissolution test for ritonavir soft gelatin capsules based on in vivo data

The purpose of the study was to develop and validate a dissolution procedure for ritonavir soft gelatin capsules (Norvir®) based on in vivo data. Several conditions such as medium composition, pH, surfactant concentration and rotation speed were evaluated. The method was carried out using the same batch of Norvir® used in a bioequivalence study and the in vivo data were used to select the best dissolution test conditions based on in vitro–in vivo correlation (IVIVC). The dissolution test was validated using a high-performance liquid chromatographic method (HPLC). For this formulation, the best dissolution conditions were achieved using paddle, 900 ml of medium containing water with 0.7% (w/v) of sodium lauryl sulfate at a rotation speed of 25 rpm. Under these conditions a significant linear relationship between fraction of ritonavir absorbed and dissolved was obtained (R2 = 0.993) and a level A IVIVC was established. In the HPLC method a relative standard deviation for intra-day precision was <1.6% and for inter-day precision was <1.4%. Accuracy was from 98.5% to 101.6% over the concentration range required for the dissolution test (4.0–124.0 μg/ml). Both the HPLC method and the dissolution test are validated and could be used to evaluate the dissolution profile of ritonavir soft gelatin capsules.