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Gadolinium (Gd)-containing microcapsules designed for neutron-capture therapy (NCT) were prepared by a spouted bed coating process. Microcapsules were designed as a Gd-reservoir. They were prepared with the following properties: particle size was smaller than 50 microns, Gd-content was as high as possible, and release of Gd was suppressed as long as possible. Calcium carbonate (20-32 microns) was selected as a speed particle. As a Gd-source, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) or a synthesized water-insoluble Gd-DTPA derivative, Gd-DTPA-distearylamide (Gd-DTPA-SA), was layered onto the seed particles. The release-suppressing layer was composed of aqueous acrylic latex of 9:9:4 poly(ethyl acrylate/methyl methacrylate/2-hydroxyethyl methacrylate). In preliminary studies, Gd-DTPA microcapsules with 41-45 microns (mass median diameter) were prepared; they released Gd with a short lag-time and 3h-prolongation. Complete release suppression was, however, difficult to achieve because of high water-solubility of Gd-DTPA. Hence, a hydrophobic derivative, Gd-DTPA-SA, was next used as a Gd source. Gd-DTPA-SA microcapsules could be prepared with a mass median diameter of 52 microns. Gd-DTPA-SA content of the microcapsules was 38% and release of Gd was suppressed to less than 0.2% over 60 d.

Design and Preparation of Gadolinium-Reservoir Microcapsules for Neutron-Capture Therapy by Means of the Wurster Process.