Microparticles for sustained release of water-soluble drug based on a containment, dry coating technology.

Controlled release microparticles in a sub-gram-scale batch were fabricated using a ball mill, dry coating technique, to coat the water-soluble core material. This process also guaranteed the maintenance of the containment's integrity during the dry coating process. Quinine (average diameter, ca. 10 μm) and carnauba wax were used as the core and coating material, respectively. We evaluated the influence of process time, milling speed, and quinine-to-carnauba wax ratio on the particle size of the coated particles and their in vitro drug release profiles. Scanning electron microscopic observations suggested that the small wax particles attached to the core (quinine) particles resulted in a smooth film during the dry coating process. The size distribution of the coated particles agreed with the theoretically estimated size distribution. The in vitro release test demonstrated that the coated particles released quinine over 2 h in a biphasic mode. These results suggest that dry coating of microparticles less than 50 µm (D99) is feasible on a several-grams-batch scale. This new ball mill-coating technique also enables a guaranteed containment, a prerequisite for the manufacturing of highly bioactive or biohazard substances.