Studies on the in-vitro percutaneous penetration of indomethacin from gel systems in hairless mice.
The influence of co-solvents on the in-vitro percutaneous penetration of indomethacin from gel systems was studied using a simplex lattice experimental design. Gel formulations were prepared by gelling the vehicle mixture of water, either alcohol or isopropanol and either propylene glycol or PEG 400 with 1% w/w Carbomer 940. Hairless mouse skin was employed as the barrier in a Franz-type diffusion cell. The penetration rates at steady state for seven formulations were fitted to a polynomial equation based on this simple lattice method and a three-dimensional plot was constructed. The formulation having the maximal penetration rate was determined to be the vehicle with a solvent ratio of water: alcohol: propylene glycol equal to 15:33:52, and which possessed a solubility parameter of 15 and a drug solubility of around 10 mg mL-1. When the solubility parameter of the vehicle was > 15, the drug solubility increased. However, the penetration rate decreased with an increasing solubility parameter. For those vehicles with a solubility parameter < 15, both the drug solubility and the penetration rate decreased with a decrease in the solubility parameter. There was shown to be an approximately 20-fold increase in the relative enhancement factor when using both alcohol and isopropanol, but only a threefold increase for both propylene glycol and PEG 400, when compared with water.
D000433:1-Propanol; D000818:Animals; D004058:Diffusion; D005782:Gels; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D011092:Polyethylene Glycols; D011409:Propylene Glycols; D012869:Skin Absorption; D014867:Water
D005782:Gels; D011409:Propylene Glycols; D014867:Water; D011092:Polyethylene Glycols; D000433:1-Propanol; D007213:Indomethacin