In vitro corneal permeability of diclofenac sodium in formulations containing cyclodextrins compared to the commercial product voltaren ophtha.
The influence of different cyclodextrin derivatives on the in vitro permeability of diclofenac sodium through pig cornea was investigated and compared to the commercial product Voltaren ophtha. (Hydroxypropyl)-beta-cyclodextrin (HP beta CD) and two amorphous methylated cyclodextrins with different degrees of substitution were used. In hemolysis studies on human erythrocytes, the hemolytic activity of the different cyclodextrins and the drug was assessed. It was shown that HP beta CD reveals the most favorable toxicological properties. A decrease in the hemolytic activity of diclofenac was yielded by adding HP beta CD. In the permeability experiments the dependency of the permeability coefficients and lag times on the type of cyclodextrin and pH of the solutions were examined. A solution containing HP beta CD buffered in the pH range 6.5 to 7 is proposed as a useful eye drop formulation. All cyclodextrin formulations showed advantages as compared to Voltaren ophtha.
Reer
O
O
Christian Albrecht University, Department of Pharmaceutics and Biopharmaceutics, Kiel, Germany.
Bock
T K
TK
Müller
B W
BW
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003505:Cyclodextrins / Q000009:adverse effects / Q000494:pharmacology*; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007509:Irritants / Q000009:adverse effects; D010477:Perfusion; D010539:Permeability; D012995:Solubility; D013552:Swine
D003505:Cyclodextrins; D007509:Irritants; D004008:Diclofenac