Dissolution mechanisms: Theoretical and experimental investigations

he dissolution behavior of a drug substance is an important part of its bioavailability. Three solid dissolution mechanisms are recognized: transport control, interface control and mixed-kinetic control. The mixed-kinetic control mechanism is not well studied as the majority of dissolution phenomena in pharmaceutical research are assumed to be transport-controlled. A phenomenological model for mixed-kinetic control was developed in which the interfacial step comprises molecular detachment and re-deposition and is described by chemical kinetic theory. This model encompasses interface control and transport control as limiting cases.;Experimental studies on three organic compounds showed that they dissolved by transport control at 37°C, but exhibited certain degrees of interface control at lower temperatures (10°C and 3°C), which, according to the model, indicates that reducing the dissolution temperature slowed down re-deposition more than transport. Using mathematical approaches derived from the model, up to 27% interface control was calculated from the experimental results.;The second experimental investigation showed significant degrees of interface control in benzoic acid dissolution in sodium dodecyl sulfate (NaDS) solutions at 25°C. The dissolution behavior was well described by the mixed-kinetic control model and up to 73% interface control was calculated. An extension of the model was proposed to describe a potential micelle-interface interaction mechanism indicated by the model-fitted parameters.;The third investigation showed that FD&C Blue...