Swelling‐controlled, constant rate delivery systems

Abstract

AbstractMaterials and conditions required for constant rate absorption of a liquid into a glassy polymer (Case II transport) have been exploited to produce prototype devices for constant rate delivery of a solute, molecularly dispersed within the polymer, to the surrounding liquid environment. Absorption of n‐hexane in polystyrene films, containing between one and two percent of Sudan Red IV dye, resulted in constant rate liberation of the colored solute to the surrounding fluid. The rate of dye release was controlled by the constant rate absorption of n‐hexane in these dye‐containing films. Companion experiments involving microtome sectioning and photomicrographic recording of dye‐loaded films, consequent to immersion in n‐hexane for various time intervals, revealed that the unpenetrated central core retained the dye originally dispersed within the film sample and, conversely, the swollen outer regions were completely denuded of dye consequent to n‐hexane penetration. The constant rate advance of the microscopically observable sharp boundary, between dye‐containing and dye‐denuded polymer, was quantitatively consistent with the independently determined kinetics of dye accumulation in the supernatant n‐hexane. These results indicate that diffusion of invading n‐hexane to the relaxing boundary and back diffusion of dye in the previously swollen outer shell are both rapid compared with the rate‐determining Case II transport of n‐hexane in these dye‐containing films. The delivery of Sudan Red IV to the n‐hexane was not confounded by an initial burst of solute, typically common to so‐called membrane‐reservoir controlled delivery devices. Swelling‐induced delivery from glassy matrices appears useful, therefore, for the design of monolithic devices for constant rate delivery over the entire course of the delivery cycle. The concept is not limited to monolithic devices; membrane‐reservoir devices could be constructed involving a glassy, solute‐containing reservoir which could be activated by penetration of invading liquid consequent to placement in a suitable fluid environment. Development of devices, suitable for swelling‐controlled release of drugs to target organs, will be based upon glassy, hydrophilic polymeric hosts.