(57) in a high shear mixture in the aqueous carrier of the surface-active agent and one or more drug solubility in the (a) water is poor, in the absence of an organic solvent, [Abstract] The present invention, the in a mixture at a temperature within a first range above the melting point of the drug solubility in water is poor, to form a heated suspension containing the drug, and said pressure range and within the first suspension heated (b) the pressurized the second temperature range below the melting point of the drug solubility in water is poor and (c) heating homogenate, and then heated to form a homogenate containing the drug is homogenized at a temperature within the range of 1 forming a homogeneous product that is stable cooling temporarily contain the agent by cooling and (d) cooling homogenate in the pressure range and the second temperature within a second range below the melting point of the drug and then and subjected to particle-stabilized energy treatment, solubility in water is poor by drying the dispersion was cooled by (e) optionally, and then forms a cooling dispersion of small particles stabilized containing drug method for producing small particles containing the drug comprising the step of forming small particles of dried containing the drug, solubility in water is poor.本発明は、(a)水への溶解性が乏しい薬剤と1種以上の表面活性物質の水性担体中の混合物を高剪断下において、有機溶媒の非存在下に、該水への溶解性が乏しい薬剤の融点以上の第1の温度範囲内で混合して、該薬剤を含む加熱サスペンションを形成し、(b)該加熱したサスペンションを第1の圧力範囲内及び該第1の温度範囲内で均質化して該薬剤を含む加熱均質化物を形成し、そして次に(c)該加熱均質化物を該水への溶解性が乏しい薬剤の融点未満の第2の温度範囲に冷却して該薬剤を含む一時的に安定な冷却された均質化物を形成し、次に(d)冷却均質化物に、該薬剤の融点未満の第2の温度範囲内及び第2の圧力範囲において、粒子安定化エネルギー処理にかけて、該薬剤を含む安定化された小粒子の冷却分散物を形成し、そして次に(e)所望によって冷却した分散物を乾燥して該水への溶解性が乏しい薬剤を含む乾燥した小粒子を形成する工程を含む、水への溶解性が乏しい薬剤を含む小粒子の製造方法に関する。
