Effect of pH and complexation on transdermal permeation of gliquidone.
Gliquidone, a second generation sulfonylurea has been investigated for transdermal delivery. The poor aqueous solubility of the drug prompted the use of hydroxypropyl-beta-cyclodextrin (HP-beta-CD), a cyclic oligosaccharide, which is known to facilitate transdermal permeation of many drugs by enhancing the solubility and thus improving the diffusible species of the drug molecules at the skin-vehicle interface. In order to optimize the transdermal delivery of gliquidone, the effect of pH along with complexation on the solubility and permeation has been investigated. The solubility profiles of the drug, on increasing the concentration of HP-beta-CD were of Higuchi's AL type at the three pH values evaluated. However, the solubilization slope of the drug at pH 7.0 was 22 times that at pH 3.0 as a result of greater intrinsic solubility of the ionized form of the drug at pH 7.0. Transdermal flux of gliquidone at pH 7.0 was significantly greater than the flux at pH 3.0 in the presence of 15% w/v HP-beta-CD, attributable to the better solubility of the drug at pH 7.0 in the presence of HP-beta-CD. The effect of increasing concentrations of HP-beta-CD investigated at variable drug loading in the donor phase at pH 7.4 endorsed the earlier observations from studies on other drugs, that the drug has to be present at saturation in HP-beta-CD aqueous vehicle to achieve an optimized flux. While at saturation, the steady state flux of gliquidone from the aqueous HP-beta-CD (25% w/v) vehicle was enhanced 31 times compared to pure drug suspension at pH 7.4, unsaturation in the donor phase resulted in the decreased flux of gliquidone. It was concluded from the present study that enhanced transdermal flux of gliquidone can be achieved by adjusting the pH and the concentration of HP-beta-CD to achieve a better solubility of the drug.
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000279:Administration, Cutaneous; D000818:Animals; D003505:Cyclodextrins; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles; D051381:Rats; D012869:Skin Absorption; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013816:Thermodynamics; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D007004:Hypoglycemic Agents; D014677:Pharmaceutical Vehicles; D013453:Sulfonylurea Compounds; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C010969:gliquidone