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, 900ml of medium containing water with 0.7% (w/v) of sodium lauryl sulfate at a rotation speed of 25rpm. Under these conditions a significant linear relationship between fraction of ritonavir absorbed and dissolved was obtained (R(2)=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 (4.0-124.0microg/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.