In vitro permeation of diclofenac salts from lyotropic liquid crystalline systems.
In this paper we examined feasible correlations between the structure of different lyotropic mesophases and transdermal administration of three diclofenac derivatives with varying degrees of kosmotropic or chaotropic properties, solubilized within the mesophases. It was found that the most chaotropic derivative of diclofenac diethyl amine (DEA-DFC) interacted with the polar heads of glycerol monooleate (GMO), thus expanding the water-lipid interface of the lamellar and cubic mesophases. This effect was detected by an increase in the lattice parameter of both mesophases, enhanced elastic properties, and increased solid-like response of the systems in the presence of DEA. Potassium diclofenac (K-DFC), a less chaotropic salt, had less pronounced effect on the structural features of the mesophases. Kosmotropic Na+ salt (Na-DFC) had only minor influence on both lamellar and cubic structures. The locus of solubilization of the molecules with the host mesophases was correlated with their delivery. It was suggested that transdermal delivery of kosmotropic Na-DFC was accelerated by the aqueous phase and less constrained by the interaction with monoglyceride. On the other hand, the chaotropic cations (K+ and DEA+), presumably entrapped in the water-lipid interface, interacted with monoglyceride headgroups, which is likely to be the key cause for their sustained administration.
Yariv
Doron
D
Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
Efrat
Rivka
R
Libster
Dima
D
Aserin
Abraham
A
Garti
Nissim
N
D000818:Animals; D020285:Cryoelectron Microscopy; D004008:Diclofenac / Q000737:chemistry / Q000493:pharmacokinetics*; D004048:Diethylamines / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000737:chemistry; D050866:Liquid Crystals / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D010539:Permeability; D011188:Potassium / Q000737:chemistry; D012867:Skin / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D012869:Skin Absorption; D012964:Sodium / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013552:Swine; D014961:X-Ray Diffraction
D004048:Diethylamines; D005989:Glycerides; D008051:Lipid Bilayers; D004008:Diclofenac; D012964:Sodium; C034281:diethylamine; C005953:monoolein; D011188:Potassium