Improvement of dissolution behavior for poorly water-soluble drug by application of cyclodextrin in extrusion process: comparison between melt extrusion and wet extrusion.
The purpose of this study was to improve dissolution behavior of poorly water-soluble drugs by application of cyclodextrin in extrusion processes, which were melt extrusion process and wet extrusion process. Indomethacin (IM) was employed as a model drug. Extrudates containing IM and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) in 1:1 w/w ratio were manufactured by both melt extrusion process and wet extrusion process. In vitro drug release properties of IM from extrudates and physiochemical properties of extrudates were investigated. The dissolution rates of IM from extrudates manufactured by melt extrusion and wet extrusion with HP-beta-CyD were significantly higher than that of the physical mixture of IM and HP-beta-CyD. In extrudate manufactured by melt extrusion, gamma-form of IM changed to amorphous completely during melt extrusion due to heating above melting point of IM. On the other hand, in extrudate manufactured by wet extrusion, gamma-form of IM changed to amorphous partially due to interaction between IM and HP-beta-CyD and mechanical agitating force during process. Application of HP-beta-CyD in extrusion process is useful for the enhancement of dissolution rate for poorly water-soluble drugs.
Yano
Hideki
H
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstr 1, 40225, Düsseldorf, Germany.
Kleinebudde
Peter
P
D000042:Absorption; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D014867:Water / Q000737:chemistry*; D017155:Wettability; D047392:beta-Cyclodextrins / Q000737:chemistry*
D005079:Excipients; D012996:Solutions; D047392:beta-Cyclodextrins; D014867:Water; C031215:betadex; D007213:Indomethacin