Effects of thermosensitivity of poly (N-isopropylacrylamide) hydrogel upon the duration of a lag phase at the beginning of drug release from the hydrogel

The release rates of three kinds of drugs, with different charges, from poly (N-isopropylacrylamide) hydrogels were studied. The release rate was observed to be temperature dependent for the types of drug. When the temperature was lower than the phase transition temperature, the release rate was higher at lower temperatures and increased as the temperature rose. The amount of drugs released from a poly (N-isopropylacrylamide) hydrogel disk was plotted against the square root of time. It was found that the amount of drugs released was proportional to the square root of time over a certain time interval. A lag phase was observed before the amount of drug released became proportional to the square root of time. The longest time lag was observed at the phase transition temperature of poly (N-isopropylacrylamide); LCST (33°C). This suggests that the penetration rate of water into the hydrogels is lowest at the phase transition temperature and drastically changes around it. The release rates of drugs was also affected by the charges of the drug molecules. This may be caused by the interaction of drug molecules with polymer chains. When anionic drugs are released, the electrostatic repulsion seems to act between polymer chains and drug molecules. Therefore, the lag phase observed at the beginning of the release of anionic drugs was shorter, as compared with other kinds of drugs at any temperatures between 25 and 40°C. On the other hand, when cationic drugs are released, the time lag was longer at temperatures higher than 33°C as compared with the time lag at lower temperatures. At temperatures higher than 33°C, drugs are released from the surface skin layer of the hydrogel where water molecules are less mobile than those in bulk distilled water. The drug release thus shows a long lag phase.