Abstract
Water diffusion into cylindrical biodegradable monolithic depots fabricated from extruded mixtures of poly(dl-lactide) and a peptidic drug, goserelin, containing 20, 30 and 40% drug by weight has been studied using an ion beam analysis technique. A series of depots were immersed in a phosphate buffered saline/heavy water solution at 37 °C for times ranging from 1 h to 7 days. One-dimensional radial profiles showing the diffusion of water into the depots were produced at points along the length of the sample and, for some short immersion times, axial profiles were obtained for the cylinder ends. The changes in weight, radius, drug release and water uptake of the depots with time were also studied. Using the water uptake measurements the one-dimensional radial profiles were normalised. From appropriate one-dimensional profiles at the shorter times Fickian diffusion coefficients were obtained for initial water diffusion. The average radial diffusion coefficients were (1.07±0.22)×10−8 cm2 s−1 for the 20% drug-loaded depots, (1.54±0.27)×10−8 cm2 s−1 for the 30% drug-loaded depots and (2.00±0.83)×10−8 cm2 s−1 for the 40% drug-loaded depots—in the ratio of the drug loadings i.e. 2:3:4, implying the water associated with drug during its uptake into the monoliths. The axial diffusion coefficients were found to be of the same order of magnitude as the radial diffusion coefficients, in accord with this hypothesis. At longer times there is a subsequent non-Fickian increase in the water concentration profile. In the case of depots loaded with 40% by weight of goserelin, the substantial fraction of the hydrophilic drug released at times greater than one day is accompanied by a decrease in radius and a decrease in water concentration near the depot surface.