Dexamethasone-cyclodextrin-polymer co-complexes in aqueous eye drops. Aqueous humor pharmacokinetics in humans.
OBJECTIVE
To test an aqueous eye drop solution containing a high concentration of dexamethasone in a cyclodextrin-based drug delivery system. This system increases both drug solubility in aqueous eye drops and drug permeability into the eye, through drug cyclodextrin-polymer co-complexes.


METHODS
2-hydroxypropyl-beta-cyclodextrin is a water-soluble oligosaccharide that can be used to dissolve lipophilic drugs, such as dexamethasone, in aqueous solutions. Co-complexation with a polymer further increases the solubility and increases drug permeability through biologic membranes. Eye drops containing dexamethasone (0.32% and 0.67%), 2-hydroxypropyl-beta-cyclodextrin, and polymer were given to patients before cataract surgery, and the resultant dexamethasone concentration was measured from aqueous humor samples.


RESULTS
The dexamethasone-cyclodextrin drops give a significantly higher concentration of dexamethasone in aqueous humor than dexamethasone alcohol 0.1% (Maxidex). Heating of the dexamethasone-cyclodextrin-polymer co-complexes appears to enhance the permeability of the drug into the eye.


CONCLUSIONS
The cyclodextrin-based drug delivery system enhances both the solubility of dexamethasone in aqueous eye drops and the permeability of the drug into the human eye. Dexamethasone concentration levels in the human aqueous humor exceed those reported with currently available steroid eye drops.
Kristinsson
J K
JK
Department of Ophthalmology, Landakotsspítali, Reykjavík, Iceland.
Fridriksdóttir
H
H
Thórisdóttir
S
S
Sigurdardóttir
A M
AM
Stefánsson
E
E
Loftsson
T
T
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D002387:Cataract Extraction; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D006358:Hot Temperature; D006801:Humans; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives; D009883:Ophthalmic Solutions; D012995:Solubility; D047392:beta-Cyclodextrins
D000893:Anti-Inflammatory Agents; D003505:Cyclodextrins; D009883:Ophthalmic Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D065347:Hypromellose Derivatives; D003907:Dexamethasone; D008747:Methylcellulose