The role of L-arginine in inclusion complexes of omeprazole with cyclodextrins.
In this study, we investigate how the effect of L-arginine (ARG) and cyclodextrins upon omeprazole (OME) stability and solubility. The effect of the presence of ARG on the apparent stability constants (K(1:1)) of the inclusion complexes formed between OME and each cyclodextrin, beta-cyclodextrin (betaCD), and methyl-beta-cyclodextrin (MbetaCD) is studied by phase solubility diagrams and nuclear magnetic resonance (NMR) spectroscopy. The interaction of OME with those cyclodextrins, in the presence of ARG, is characterized using NMR spectroscopy and molecular dynamics simulations. ARG significantly increases the drug solubility and complex stability, in comparison to inclusion complexes formed in its absence. The effect is more pronounced for the OME:betaCD complex. ARG also contributes to a larger stability of OME when free in aqueous solution. The combination of ARG with cyclodextrins can represent an important tool to develop stable drug formulations.
CICS, Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal.
Ana
A
Figueiras
Jorge M G
JM
Sarraguça
Alberto A C C
AA
Pais
Rui A
RA
Carvalho
J Francisco
JF
Veiga
D001120:Arginine; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D009853:Omeprazole / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D047392:beta-Cyclodextrins / Q000737:chemistry*
D003505:Cyclodextrins; D012996:Solutions; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D001120:Arginine; C031215:betadex; D009853:Omeprazole