Investigation on different levels of in vitro-in vivo correlation: gemfibrozil immediate release capsule

Gemfibrozil is a practically water-insoluble, high-dose drug. It represents a typical drug with dissolution rate controlled bioavailability. The aim of this study was to select a dissolution condition for gemfibrozil immediate release capsules, resulting in the best in vitro/in vivo correlation (IVIVC). Five 300 mg gemfibrozil products, including the innovator and four generic products were selected. In vitro dissolution test methods with a standard paddle, round-bottomed vessel of 1 l capacity, and potassium phosphate buffer as the dissolution medium (referred to as conditions I, II and III, respectively) were developed. The products were administered to 12 healthy volunteers and thereby different pharmacokinetic parameters were calculated. Correlations between the in vitro and in vivo calculated parameters were investigated. Of the single point parameters investigated, the best results were seen in the relation between the percent dissolved in 10, 20 and 45 min and the time to 90% dissolution from the in vitro side and the AUCs and C(max) from the in vivo side. The correlation between MRT and MDT was also investigated, and no significant correlation was found in the three above-mentioned conditions. The Wagner-Nelson method was used to calculate the percent remaining to be absorbed. Superimposition of the percent in vivo absorption and the in vitro dissolution curves was used to investigate a multiple point correlation. A remarkable superimposition between in vivo and in vitro curves in conditions I and II was observed.