Phase solubility behavior of hydrophilic polymer/cyclodextrin/lansoprazole ternary system studied at high polymer concentration and by response surface methodology.
Evaluation of polymer/cyclodextrin (CD)/drug ternary systems has been performed at low polymer levels to date, and the cross-interaction of polymers and CDs has not been well studied. In this study, the effects of PVP K30 and PEG 6000 on the complexation ability of β-CD and 2-hydroxypropyl-β-cyclodextrin (HPCD) with lansoprazole (LSP) was investigated. The phase solubility of polymer/CD/LSP ternary systems was first studied at polymer levels of 0%, 2% and 6%, respectively. A response surface methodology was then employed to investigate the cross-interaction of polymers/CDs on phase solubility at polymer levels up to 10%. Results indicated A(L)-type inclusion for both β-CD and HPCD. Increase in PEG concentration leads to improved complexation efficiency, whereas increase of PVP lead to decreased CE, which is attributable to the strong interaction between PVP and LSP. Second-order polynomial equations were well employed to estimate the relationship between LSP solubility and the two independent variables. The response surface showed that PVP and PEG had no significant effects on LSP/CD complexation, while a synergistic effect on LSP solubility was observed at higher concentrations of HPCD and PEG. It is concluded that high levels of polymer lead to increased LSP solubility but not significant increase in CE.
School of Pharmacy, Fudan University, Shanghai 201203, PR China.
Yi
Y
Lu
Ning
N
Tang
Jianping
J
Qi
Wei
W
Wu
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D064747:Lansoprazole; D010592:Pharmaceutic Aids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000890:Anti-Infective Agents; D005079:Excipients; D010592:Pharmaceutic Aids; D047392:beta-Cyclodextrins; D064747:Lansoprazole; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011092:Polyethylene Glycols; D011205:Povidone; C031215:betadex