DESIGN AND PREPARATION OF ETHYL CELLULOSE MICROCAPSULES OF GADOPENTETATE DIMEGLUMINE FOR NEUTRON-CAPTURE THERAPY USING THE WURSTER PROCESS

Microcapsules of hygroscopic, highly water-soluble gadopentetate dimeg lumine (Gd-DTPA-DM) for use in preliminary in vivo experiments for neu tron-capture therapy were designed. They were prepared with such prope rties as a particle size small enough to be suspended and injected thr ough a syringe, a negligible release of Gd-DTPA-DM, and a high drug co ntent by means of the Wurster process, a spray coating method using a spouted bed with a draft tube. They were composed of lactose cores of 53-63 mum, an undercoat of ethyl cellulose (EC) and polyvinylpyrrolido ne (PVP), a drug-layer of Gd-DT-PA-DM, EC and PVP, a waterproof coat a nd a release-sustaining overcoat of EC and cholesterol (1 : 1), and a surface treated with hydrogenated egg lecithin. By curing at 110-degre es-C for 30 min after mixing with 20% pulverized mannitol powder, the 20% overcoating suppressed the release of Gd-DTPA-DM from 75-106 mum m icrocapsules to less than 10% for the first 20 min, which was the peri od required to prepare a suspension, inject it and irradiate the neutr on. The microcapsules could be used to confirm that the intracellular presence of Gd is not critical in gadolinium neutron-capture therapy.