Design and preparation of gadolinium-reservoir microcapsules for neutron-capture therapy by means of the Wurster process.
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.
Miyamoto
M
M
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Ichikawa
H
H
Fukumori
Y
Y
Akine
Y
Y
Tokuuye
K
K
D000179:Acrylates / Q000737:chemistry; D002119:Calcium Carbonate / Q000737:chemistry; D002214:Capsules / Q000032:analysis; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005682:Gadolinium / Q000032:analysis*; D019786:Gadolinium DTPA / Q000032:analysis*; D006801:Humans; D020366:Methylmethacrylate; D008768:Methylmethacrylates / Q000737:chemistry; D009369:Neoplasms / Q000532:radiotherapy; D017247:Neutron Capture Therapy; D010316:Particle Size; D013229:Stearic Acids / Q000032:analysis
D000179:Acrylates; D002214:Capsules; D003692:Delayed-Action Preparations; D008768:Methylmethacrylates; D013229:Stearic Acids; D020366:Methylmethacrylate; C031183:stearic acid; C040833:ethyl acrylate; D005682:Gadolinium; D002119:Calcium Carbonate; D019786:Gadolinium DTPA