Effect of temperature on imipramine hydrochloride permeation: role of lipid bilayer arrangement and chemical composition of rat skin.
The aim of this investigation was to study the effect of temperature on the permeation of imipramine hydrochloride (IMH) across rat skin from two different vehicles. Differential scanning calorimetry (DSC) was used to characterize the phase transitions of rat epidermis and extracted rat SC lipids, and the transition temperatures were correlated with the permeability of IMH at different temperatures. Permeability of IMH from ethanol and propylene glycol (PG) was determined at five different temperatures and observed that a significant increase in IMH permeability occurred 45 degrees C from both the vehicles. Further, high energies of activation for rat skin permeation suggested that IMH diffuses across intercellular lipid matrix and therefore any change in the packing of SC lipids will have an effect on IMH permeation. Three endotherms T(1), T(2) and T(3) of rat epidermis were observed in DSC thermograms at 44, 53 and 64 degrees C and were assigned as transitions corresponding to orthorhombic to hexagonal, hexagonal to more disordered phase and melting of lipids with high cholesterol content, respectively. The high permeability values of IMH above 45 degrees C were therefore reasoned to be because of orthorhombic to hexagonal phase transition in rat skin from close to that temperature.
Jain
Amit Kumar
AK
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, Phase-X, SAS Nagar, Mohali 160 062, Punjab, India.
Panchagnula
Ramesh
R
D000818:Animals; D002152:Calorimetry, Differential Scanning; D007099:Imipramine / Q000008:administration & dosage*; D008051:Lipid Bilayers / Q000378:metabolism*; D008055:Lipids / Q000032:analysis*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature
D008051:Lipid Bilayers; D008055:Lipids; D007099:Imipramine