Kinetics, mechanisms and in vitro measurement of drug liberation from suppositories

The release of suspended caffeine and theobromine from suppositories produced with four types of hard fat (Witepsol®) with selected chemical compositions were measured with two models differing in such a manner that spreading and sedimentation of the drug particles have different influences on the liberation rates. The release of both the drug substances depends on the particle size distribut and on the base which they are compounded with. A detailed interpretation of the measured liberation profiles leads to the conclusion that the vehicle influence is caused by interactions of hard fat components with the vehicle surface competing with wetting by the hydrophilic phase. Further, the structuring of the sediment and the displacement of the base from the interparticular spaces by water depend on the rheological properties of the vehicle melt so that an influence of the particle size distribution on the vehicle effect results. These parameters can participate in the rate control under suited conditions. The liberation rate measurements are evaluated by fitting computations with a modified Weibull's equation taking the lag time into account. The first differentiation of this equation gives a function of the release rate in dependence on time which is of interest with regard to be sustained release character of suppositories and to the drug liberation mechanisms