Enhanced permeation of methotrexate in vitro by ion pair formation with L-arginine.
Ion paired solutions of methotrexate in L-arginine/water/propylene glycol systems were evaluated for their potential to enhance the permeation of methotrexate across rabbit nasal mucosa in vitro. The partition coefficient of methotrexate in the methotrexate: L-arginine ion paired systems was observed to be 24 times greater than that of the methotrexate system without L-arginine. The ion pair formation between methotrexate and L-arginine was confirmed by a decrease in the conductivity of the systems in the presence of propylene glycol, a dielectric constant reducing agent. The permeation of methotrexate across the rabbit nasal mucosa from the ion paired systems was observed to be significantly greater (p < 0.05) as compared to control systems of methotrexate solution in water and a sodium salt. Furthermore, a threefold increase in the flux of methotrexate was observed when propylene glycol was added to the ion paired systems. These results suggest that methotrexate: L-arginine ion paired systems have potential in improving the permeation of methotrexate across rabbit nasal mucosa and may form the basis for further development of an intranasal therapeutic system of methotrexate.
Ivaturi
Vijay D
VD
College of Pharmacy and Allied Health Professions, St John's University, Queens, New York 11439, USA. ivatu001@umn.edu
Kim
S Kwonho
SK
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000493:pharmacokinetics*; D001120:Arginine / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D004355:Drug Stability; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008727:Methotrexate / Q000737:chemistry* / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000378:metabolism; D014677:Pharmaceutical Vehicles; D019946:Propylene Glycol; D011817:Rabbits; D012995:Solubility
D000964:Antimetabolites, Antineoplastic; D014677:Pharmaceutical Vehicles; D019946:Propylene Glycol; D001120:Arginine; D008727:Methotrexate