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Preparation of nano-and submicron sized particles is a useful method for solubility improvement of poorly watersoluble drugs of oral dosage forms by increasing surface area. In this study, a multi-ring type wet milling system was used to micronize poorly water-soluble drugs, and its performance was investigated. It was confirmed that particle size was easy to control by the operating conditions with adding a little quantity of milling stabilizer. Also, it was considered that a low content of additives is very advantageous in regard to the choice of formulation and characteristics of the final drug products. As a result, the dissolution profiles of ibuprofen and indomethacin which were milled in this study were faster than the non-milled original drugs, and their suspensions were stable for a week without having agglomeration, and the crystallites of the milled drugs were maintained. Also, the usage of the multiring type wet milling system would make easy to determine the scale-up operating conditions from the point of view of the milling mechanism, and a high content of drug substances is advantageous for the manufacturing.

Solid dispersion particles were prepared using an indomethacin (IND) as a model insoluble drug, poly-(vinylpyrrolidone-co-vinyl acetate) (VA64) as a water-soluble polymer and mannitol (Man) as an excipient. In case of hot-melt extrusion (HME) preparation, dissolution profile of every composition without Man was the same as others. The dissolution profile of composition including Man was much improved than others without Man. By contrast, the effect of Man addition was not recognized in case of spray drying (SD) preparation. Surface energy of the solid dispersion particles was measured by using an inverse gas chromatography surface analyzer (iGC-SEA). The surface energy of solid dispersion particles including Man prepared by the HME is much smaller than that without Man. However, in the SD preparation, there was no clear difference in the surface energy of solid dispersion particles with and without Man. The characteristic of the solid dispersion particles by the different manufacturing methods implied the difference of the dissolution improvement, in spite of the same composition.

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