Design of dry nanosuspension with highly spontaneous dispersible characteristics to develop solubilized formulation for poorly water-soluble drugs.

Purpose: The powderization of the aqueous nanosuspension of a poorly water-soluble drug, which was prepared by wet-milling technique developed by authors, was investigated to apply to the development of solid dosage forms.

Methods: Drug particles were suspended and milled in the aqueous medium using the oscillating beads-milling apparatus. The recovered nanosuspension was spray-dried 1) with no additive or 2) with co-dissolving mannitol as a nanoparticle carrier. As a control, the solution of the drug and additives with the same formulation as nanosuspension was also spray-dried.

Results: SEM observation and X-ray powder diffraction analysis revealed that the dried products from suspension formed a spherical particle with single-micron diameter, which was composed of thousands of nano-sized crystalline drug fragment. It was also found that the dried products from suspension could be spontaneously redispersed in water, transforming into nanosuspension with the original size distribution. Such dried powder with high dispersibility was named "dry nanosuspension." The dry nanosuspension had immediate release behaviors in gastrointestinal buffered media, whereas the dried product from solution showed the poor dispersion and dissolution properties even if same content of additives were loaded.

Conclusions: The present technique with combination of wet nano-milling and spray-drying processes would be a novel approach to develop the pharmaceutical products with poorly water-soluble and oral-absorbable drugs.