| 摘要 |
FIELD: pharmaceutical industry. ^ SUBSTANCE: process comprises following stages: (a) preparing solution of raw material containing therapeutical agent and concentration-increasing polymer dissolved in a solvent; (b) passing resulting solution to spray-drying apparatus comprising drying chamber, spraying device to spray above-mentioned solution into droplets in indicated draying chamber, source of above-mentioned drying gas to be heated and to dry above-mentioned droplets, and drying product collection apparatus; (c) spraying raw material solution into droplets in drying chamber with the aid of above-mentioned drying device, average diameter of droplets being at least 50 mum and D10 at least 10 mum; (d) bringing droplets into contact with drying gas being heated to form particles of solid amorphous disperse system consisting of above-mentioned therapeutical agent and above-mentioned concentration-increasing polymer, wherein therapeutical agent fraction is present in relatively pure amorphous zone in disperse system is below 20% of the total amount of therapeutical agent and wherein concentration-increasing polymer is present in solution in sufficient amount; and (e) collecting above-indicated particles. Solid amorphous disperse system ensures: (i) maximum concentration of therapeutical agent in application medium, which is at least 1.25-fold concentration of therapeutical agent relative to concentration of reference composition and (ii) surface area under concentration curve relative to time curve in application medium over any 90 min period starting at time point of introduction into application medium and ending at about 270 min after indicated introduction, which is at least about 1.25 times superior to this characteristics in above-mentioned reference composition, which, in this case, consists essentially of equivalent amount of therapeutical agent. In another embodiment of invention, process comprises similar stages (a), (b), and (e), while stages (c) and (d) comprise: (c) spraying raw material into droplets in drying chamber with the aid of spraying device and (d) bringing droplets into contact with drying gas being heated to form particles of solid amorphous disperse system consisting of above-mentioned therapeutical agent and above-mentioned concentration-increasing polymer, wherein therapeutical agent fraction is present in relatively pure amorphous zone in disperse system is below 20% of the total amount of therapeutical agent, said particles having average diameter 40 mum or larger and less than 10% of the particles have average diameter less than about 8 mum. Polymer is present in this solution in sufficient amount so that solid amorphous therapeutical disperse system provides increasing composition of therapeutical agent in application system relative to reference composition consisting essentially of equivalent amount of therapeutical agent. ^ EFFECT: improved rheological properties of systems and increased yield of product. ^ 14 cl, 7 dwg, 13 tbl, 6 ex |
