公开(公告)号：WO2019040346A1

公开(公告)日：2019-02-28

申请号：PCT/US2018/047015

申请日：2018-08-20

申请人： MERCK SHARP & DOHME CORP. ,  LEUNG, Dennis, H. ,  GUO, Zhiqiang ,  BOYCE, Christopher, W.

发明人： LEUNG, Dennis, H. ,  GUO, Zhiqiang ,  BOYCE, Christopher, W.

IPC分类号： A61K9/14 ,  A61K9/16

CPC分类号： A61K9/146 ,  A61K9/0095 ,  A61K9/10 ,  A61K9/145 ,  A61K9/2004 ,  A61K9/48 ,  A61K47/10 ,  A61K47/38

摘要： The present invention relates to methods for producing a stable amorphous dispersion of a pharmaceutically active substance having poor water solubility by applying low frequency acoustic energy to a mixture comprising the active substance and at least one polymer and heating the mixture until a stable amorphous dispersion is formed. The methods of the invention are an effective means of converting a crystalline API to a substantially amorphous and stable form, i.e., wherein the crystallinity is less than about 5%. The methods of the invention result in more complete amorphization, increased solubility, drug loading and stability as compared to typical amorphization or literature methods.