Abstract
Conventional monolithic devices in which drug is uniformally dispersed shows a first order release. More specifically, the drug release rate from the monolithic devices continuously diminishes with time. To achieve zero order release, monolithic device having heterogeneous polymer structure was synthesized and drug release pattern in phosphate buffer saline solution from these devices were compared to homogeneous monolithic devices. Heterogeneous devices that poly(acrylamide) (PAAm) beads were dispersed in poly (2-hydroxy ethyl methacrylate) (HEMA) or random copolymer of HEMA with butyl methacrylate(BMA) were synthesized. These devices were soaked in sodium salicylate solution. Drug was selectively loaded into PAAm beads for the difference of partition coefficient between PAAm beads and surrounding polymeric matrices, At low loading, the release pattern from heterogeneous devices approached to zero order release. This can be explained in terms of release regulating function of polymeric matrices surrounding PAAm beads. At high loading, burst release was observed due to an increase in water content by hydrophilicity of the drug. It was concluded that zero order release could be achieved by regulating hydrophilicity of the drug and polymeric matrices, beads content, drug loading amount and drug distribution in the polymeric devices.
