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    • 1. 发明申请
    • MOISTURE-ACTIVATED GRANULATION PROCESS
    • 水分活化成粒过程
    • WO2010089105A3
    • 2011-01-13
    • PCT/EP2010000667
    • 2010-02-03
    • KRKA TOVARNA ZDRAVIL D D NOVO MESTOSTUKELJ MITJASKRABANJA VIDAFERLAN ANDREJVRECER FRANCKUKEC SIMON
    • STUKELJ MITJASKRABANJA VIDAFERLAN ANDREJVRECER FRANCKUKEC SIMON
    • A61K31/165A61K9/20A61K9/26A61K31/4985
    • A61K9/2077A61K31/165A61K31/4985
    • The present invention relates to a moisture-activated granulation process for the manufacture of a pharmaceutical dosage form containing at least one moisture- sensitive active substance selected from the group consisting of aliskiren and its pharmaceutically acceptable salts, esters and cocrystals, said process comprising: a) mixing the active substance (s) with one or more dry excipients in solid form, said excipient being selected in particular from the group consisting of diluents, surfactants, binders, lubricants, disintegrators, granulation aids, buffering/alkalizing agents, fillers and antioxidants; b) contacting the mixture with a granulation liquid containing water and optionally one or more excipients to form a granulate, said excipient being selected in particular from the group consisting of binders, buffering/ alkalizing agents, surfactants and antioxidants, to form a granulate wherein the ratio of the total amount of water to the total amount of all the solid ingredients including the active substance (s) and all intragranular excipients is less than 30:100, based on weight; c) further processing the mixture including the addition of further dry excipients to obtain the pharmaceutical dosage form, said excipients being in particular selected from the group consisting of diluents, disintegrants, glidants and lubricants.
    • 本发明涉及一种用于制造含有至少一种选自阿利吉仑及其药学上可接受的盐,酯和共晶体的湿敏活性物质的药物剂型的水分激活造粒方法,所述方法包括: 将活性物质与一种或多种固体形式的干燥赋形剂混合,所述赋形剂特别选自稀释剂,表面活性剂,粘合剂,润滑剂,崩解剂,造粒助剂,缓冲/碱化剂,填料和抗氧化剂 ; b)使混合物与含有水和任选的一种或多种赋形剂的造粒液接触以形成颗粒,所述赋形剂特别选自粘合剂,缓冲/碱化剂,表面活性剂和抗氧化剂,以形成颗粒,其中 基于重量,水的总量与包括活性物质和所有颗粒内赋形剂的所有固体成分的总量的比例小于30:100; c)进一步处理混合物,包括加入另外的干燥赋形剂以获得药物剂型,所述赋形剂特别选自稀释剂,崩解剂,助流剂和润滑剂。