(440a) Nanoparticle Formation of Highly Water-Soluble Pharmaceutical Coated with Poorly Water-Soluble Material by Using the Rapid Expansion of Water-in-Supercritical CO2 Microemulsion

A novel technique for nanoparticle production and nanoparticle encapsulation are investigated using the rapid expansion of water-in-supercritical CO2 microemulsion. The aqueous cores of micellar nanodroplets filled up with Gd-DPTA, highly water-soluble anticancer drug, are formed and dispersed in the supercritical CO2 to form the inverse microemulsion system. The rapid expansion of the supercritical microemulsion into the atmosphere is then carried out for the production of Gd-DPTA nanoparticle. For Gd-DPTA particle encapsulation, paraffin, encapsulating material, is additionally dissolved into the supercritical CO2 phase. The morphologies of particle samples are examined by the SEM and TEM observation with EDS analysis.　The composite nanoparticles consisted of AOT and Gd-DPTA were success fully produced at the average size of 350 nm and relatively narrow size distribution. During the rapid expansion process, the supersaturation of AOT dissolved at the interface of polar micelle filled up with Gd-DPTA and supercritical CO2 take place. The precipitation of AOT capturing Gd-DPTA micelles leads to the formation of the composite particle. In addition, the composite particle of AOT and Gd-DPTA was successfully encapsulated with paraffin with a coating layer in nanoscale. During the rapid expansion, the supersaturation of AOT, dissolved at the interface of polar micelle filled up with Gd-DPTA and supercritical CO2, and the supersaturation of paraffin dissolved in the supercritical CO2 take place. Then, the precipitated paraffin nuclei are likely to deposit on the surface of the Gd-AOT composite particle precipitated simultaneously, leading to the encapsulation with paraffin. The sizes of the micelles seemed to play a significant role in mechanism of particle production and particle encapsulation. The results obtained have demonstrated that the rapid expansion of water-in-supercritical CO2 microemulsion is a promising method for continual combination of nanoparticle production and their encapsulation, especially for highly water-soluble pharmaceuticals.