Investigation of drug release from suspension using FTIR-ATR technique: part II. Determination of dissolution coefficient of drugs

Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy was applied to a release experiment in order to determine the dissolution coefficient of drug particles in heterogeneous semisolid formulations. The drug release experiment was carried out using ketoconazole suspended in Vaseline with various amounts of paraffinum liquidum as donor and an artificial dodecanol-collodion (DDC) membrane as acceptor compartment. Monitoring changes in IR bands due to ketoconazole the decrease of the drug content near the ATR crystal ointment was followed as a function of time. A mathematical model based on Fick's second law with a source term was used to derive the apparent dissolution coefficient K-dis by numerical fitting the experimental data. It was found that K-dis is dependent on the fraction of paraffinum liquidum in the suspension. Taking into account all experimental parameters required, the transport process was simulated and discussed in terms of drug concentration - time and drug concentration - distance profiles. Calculating the area under the mass - time curve it was tried to predict the 'dermal bioavailability' in the acceptor (AUC(a)). (C) 2000 Published by Elsevier Science B.V.