Design of swellable ordered-mixed spherical drug particles (Swell-OM-spheres) using a dry powder milling and coating technique to improve dissolution behavior

Abstract

A novel dry powder milling/ordered-mixing technique using a mechanical powder processor was previously developed to improve the dissolution properties of poorly water-soluble drugs. Mecanofused composite particles with an ordered-mixing principle, named OM particles, were designed using corn starch (CS) as a core particle and drug as a coating layer. In the present study this dry powder processing technique was modified to improve the dissolution behavior further by means of two approaches. First, wettable composite particles were produced by co-formulating the water-soluble waxy additive to enhance the hydrophilicity of the outer drug layer. Second, swellable composite particles were designed by replacing CS with a modified starch having expanding property as the core particle. It was found that the latter (swellable) approach was more effective than the former (wettable) one to improve the dissolution behavior of poorly water-soluble model drug. The swellable OM particles promptly expanded on contact with water and induced the effective detachment of fine drug particles from the core particles, resulting in rapid drug release. The present research suggests that the proposed contamination-free dry milling technique, which does not use hard milling balls or beads, can generate spherical drug particles with improved dissolution characteristics.