In vivo evaluation of rapid release and sustained release Gelucire capsule formulations

Abstract

Ketoprofen was dispersed in a water miscible, highly ethoxylated wax and filled into hard gelatin capsules. This produced drug absorption equivalent in rate and extent to conventional rapid release formulations. Where gastric spreading/dispersion was slow, gastric emptying was delayed and the rate of drug absorption reduced. The use of a slowly hydrating, erodible wax formulation was shown to produce sustained release in vivo, prolonging drug levels relative to conventional formulations. Good in vitro-in vivo correlation was not observed and a relative bioavailability lower than expected was determined. However, comparing the semi-solid ketoprofen capsule (100 mg) plasma data with the comparable product (Oruvail 200 mg) by normalizing for a 200 mg dose, it is apparent that the two formulations are likely to yield similar terminal plasma concentrations. Controlled drug release was not achieved and drug absorption was dependent upon physiological variables such as gastric emptying and intestinal transit as assessed by gamma scintigraphy. In vitro differences in dissolution profiles between freshly manufactured and stored capsules, were shown not to be significant in vivo. Special storage conditions to ensure reproducible release behaviour should therefore be unnecessary.