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A negatively thermosensitive drug-release microcapsule with hydroxypropyl cellulose (HPC) coat was designed and its preparation was carried out by using an air suspension coating technique (the Wurster process). The microcapsule had a core of calcium carbonate, a drug layer of carbazochrome sodium sulfonate (model drug), a subcoat of temperature-insensitive, water-insoluble ethylcellulose (EC), a thermosensitive layer of HPC having a lower critical solution temperature (LCST) and an overcoat of EC. Three different grades of commercial HPC were used. No significant thermosensitivity of drug release was found in the microcapsules (MCs) without the overcoat of EC. However, MCs having the overcoat showed a negative thermosensitivity : the release rate suddenly decreased at temperatures close to the spectrophotometrically determined LCST of each dilute HPC sulution. These results demonstrated that by simply constructing an LCST polymer layer sandwiched between EC membranes, devices exhibiting negatively thermosensitive drug-release could by obtained in the form of fine microcapsules and the temperature dependence of release could be altered depending on the solution properties of the polymers used.

Negatively Thennosensitive Release of Drug from Microcapsules with Hydroxypropyl Cellulose Membranes Prepared by the Wurster Process.