Solubilization and stabilization of sodium dicloxacillin by cyclodextrin inclusion.
The aim of this work is to analyze the effect of cyclodextrin (CD) complexation on the solubilization and stabilization of sodium dicloxacillin in acid aqueous solutions. The effect of four cyclodextrins alpha-, beta-, gamma- and hydroxypropyl-beta-CD was studied. Phase solubility diagrams obtained are AL or BS type, depending on the cyclodextrin used and on the pH of the solution. The highest stability constants of the inclusion complexes are obtained with gamma-CD at pH 1 and 2 and HPbeta-CD at pH 3. The structure of the inclusion complex in solution is characterized by nuclear magnetic resonance (1H-NMR). This study suggests that the 7-oxo-4-thia-1-azabicyclo group is located in the CD cavity. Nevertheless, molecular modelling calculations predict two different orientations of dicloxacillin in the gamma-CD cavity in vacuum and in aqueous solution. In vacuum, the results predict the inclusion of the dichlorophenyl ring of dicloxacillin instead of 7-oxo-4-thia-1-azabicyclo group into the gamma-CD cavity. However, the results are different in aqueous solution and this conformation is confirmed by the NMR study. The effect of gamma-CD and HPbeta-CD in the stability of the drug in solution was studied. The degradation of sodium dicloxacillin in solution follows a pseudo-first-order kinetics and the cyclodextrin do not change this fact. Both cyclodextrins increase the stability of the drug but the efficacy is higher with gamma-CD.
Echezarreta-López
María Magdalena
MM
Departamento de Farmacia e Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Sur, Santiago de Compostela, Spain.
Otero-Mazoy
Iria
I
Ramírez
Héctor Luís
HL
Villalonga
Reynaldo
R
Torres-Labandeira
Juan José
JJ
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D003505:Cyclodextrins / Q000737:chemistry*; D004009:Dicloxacillin / Q000737:chemistry*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D047391:alpha-Cyclodextrins / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry; D047408:gamma-Cyclodextrins / Q000737:chemistry
D000900:Anti-Bacterial Agents; D003505:Cyclodextrins; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004009:Dicloxacillin