Characterising drug release processes within controlled release dosage forms using the confocal laser scanning microscope

A new method has been developed for quantifying drug release processes within controlled release dosage forms using the confocal laser scanning microscope (CLSM). The changing internal distribution of a fluorescent marker drug (minocycline HCl) within a spherical controlled release pellet undergoing drug release was followed using CLSM, which allowed internal mapping of the drug non-invasively and without prior sample preparation. Image analysis routines were developed to quantify the changing drug concentration profile with time across the radius of the pellet, and the results were fitted to a theoretically derived mathematical model which predicted a biphasic depletion mechanism. The experimental results closely fitted the predicted profile, and enabled calculation of the drug dissolution rate constant, the diffusion coefficient of drug within the matrix, and the time drug dissolution within the matrix ended.