Confined nano-crystallization of celecoxib inside porous mannitol

• We developed novel nano-crystallization technique of drugs.
• Directional crystallization was followed by confined crystallization of drug.
• This can replace the current processing-intensive nanocrystal technologies.
• Distinctly improved dissolution characteristics were obtained.

Improving the dissolution behavior of poorly or sparingly water-soluble drugs by reducing their particle size remains a critical issue in oral drug delivery. Confined nano-crystallization has many advantages over other nanocrystal preparation techniques, but also has the serious drawback of the use of uncommon excipients as porous template materials. We prepared novel porous mannitol templates with pore sizes ranging from a few microns to submicrons by directional melt crystallization of solvent; these pores served to confine the evaporative crystallization of celecoxib. Pore structures were relatively well connected, which was beneficial for infiltration of the drug solution. The particle size of the resulting crystals spanned from tens of microns to several hundreds of nanometers. Distinctly improved dissolution characteristics were obtained with retention of the stable original polymorph. We anticipate the readily dissolvable composite formulation of mannitol and celecoxib described in this study will spur the development of nanocrystal formulations for various poorly water-soluble drugs.