Abstract
Poly(N-isopropyl acrylamide) (IPAAm) has characteristics to exhibit a remarkable swelling change in aqueous system in response to a change of temperature. Random copolymers of IPAAm with alkyl methacrylate (RMA) having different length of alkyl chain were systhesized to clarify the effect of the hydrophobic structure on thermo-sensitive swelling behaviors. Indomethacin was loaded into these polymers and drug relase experiment was performed. At constant temperature, release pattern was observed as zero order release pattern when temperature was low. This can be explained in terms of a permeability increase in polymeric matrices after the durg was released, because the loaded hydrophobic drug suppress the swelling of polymeric matrices. New equation based on the swelling change in the process of the drug releasing was derived and a good agreement was found between the experimental results and the theoretical release simulation. Pulsatile release patterns were found to be regulated by temperature flactuation between 20°C and 30°C. This ON-OFF release mechanism is due to surface shrinking layer with an increase in temperature. The formation process of these shrinking layers were dependent on alkyl chain length of RMA. When the period of OFF drug release state was enlarged, drug release rate in ON state was maintained constant before and after OFF state. The results suggested that loaded drug in polymeric matrices migrated to the surface during OFF state even if the drug release was completely stooped.
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