A NEW MODEL FOR ZERO-ORDER DRUG RELEASE .1. HYDROPHOBIC DRUG RELEASE FROM HYDROPHILIC POLYMERIC MATRICES

Conventional monolithic drug delivery devices in which drug is uniformly dispersed typically show square-root-of-time release rates. To achieve zero-order release, monolithic devices of hydrophilic polymer were prepared, loaded with hydrophobic drug. Hydrophobic indomethacin was loaded into hydrophilic matrices of poly(N-isopropyl acrylamide(IPAAm)-co-alkyl methacrylate(RMA)) whose hydrophilicity can be varied by temperature without changing the chemical structure. Drug release experiments were performed in phosphate buffered saline. Under conditions of high drug loading in highly hydrophilic polymeric matrices, the release patterns were observed to be nearly zero-order. This result can be explained in terms of increasing diffusivity in polymeric matrices after drug is released, because loaded hydrophobic drug suppresses the swelling of polymeric matrices. A new equation predicting drug release based on diffusivity changes of the polymeric matrices was derived and a good agreement was found between the experimental results and the theoretical release simulation.