Utility of nuclear magnetic resonance spectroscopy to characterize the structure of dexamethasone sodium phosphate inclusion complexes with cyclodextrins in solution and to analyze potential competitive effects.
The interaction between dexamethasone sodium phosphate (DSP) and four cyclodextrin (CyD) derivatives [2,6-di-O-beta-cyclodextrin (DIMEB), gamma-cyclodextrin (gamma-CyD), and hydroxypropyl-beta-cyclodextrin with either 2.7 or 4.6 degrees of substitution (HPbetaCyD 2.7 and HPbetaCyD 4.6, respectively)] was investigated by proton nuclear magnetic resonance spectroscopy (1H NMR). The data suggested the formation of inclusion complexes in solution in which B and C rings of the molecule are located inside the cavity. Nevertheless, the structure, in terms of depth within CyD, depends on the derivative considered. Molecular mechanics calculations of DSP complexes with DIMEB and gamma-CyD support the NMR results. The potential displacement of DSP from the CyD cavity by usual ophthalmic drugs (e.g., polymyxin B, trimethoprim, and benzalkonium chloride) was determined by NMR. The technique has been found useful to analyze this problem in pharmaceutical preparations.
Departamento de Farmacia e Tecnoloxía Farmacéutica, Facultade de Farmacia, Universidade de Santiago de Compostela, Campus Universitario Sur, E-15782 Santiago de Compostela, Spain.
M M
MM
Echezarreta-López
I
I
Perdomo-López
E
E
Estrada
J L
JL
Vila-Jato
J J
JJ
Torres-Labandeira
D000900:Anti-Bacterial Agents / Q000737:chemistry; D001548:Benzalkonium Compounds / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000737:chemistry*; D005493:Folic Acid Antagonists / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D011112:Polymyxin B / Q000737:chemistry; D011310:Preservatives, Pharmaceutical / Q000737:chemistry; D012996:Solutions; D014295:Trimethoprim / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001548:Benzalkonium Compounds; D003505:Cyclodextrins; D005493:Folic Acid Antagonists; D011310:Preservatives, Pharmaceutical; D012996:Solutions; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; D014295:Trimethoprim; D011112:Polymyxin B