Effects of the Various Solvents on the In vitro Permeability of Indomethacin through Whole Abdominal Rat Skin

Purpose: The aim of the present study was to evaluate the effect of some solvents on in vitro dermal absorption of indomethacin.
Methods: The effects of different solvents such as Plurololeique, Labrasol, Tween 80, Isopropyl myristate and PEG 400 on indomethacin permeation through pretreated rat skin were evaluated. A specially designed Franz diffusion cell was used and the data were compared to the results of hydrated abdominal rat skin as a common control. The measured permeability parameters included permeability coefficient (Kp), diffusion coefficient (D) and flux (Jss). Enhancement mechanisms were studied by comparing changes in peak wave number position and their intensities of asymmetric (Asy) and symmetric (Sym) C-H stretching, lipid ester carbonyl stretching in SC, C=O stretching (Amide I) and C-N stretching of keratin (Amide II) absorbance using Fourier transform infrared spectroscopy (FTIR). Using differential scanning calorimetry (DSC), their mean transition temperature (Tm) and enthalpies (ΔH) were also compared.
Results: All the solvent materials significantly increased flux (Jss) (p<0.05), with isopropyl myristate showing the greatest enhancement ratio (ERflux) based on flux followed by Tween 80, plurololeique, polyethylene glycol 400 and labrasol. The ERflux for all the solvents was higher than ERD. Plurololeique, isopropyl myristate and Tween 80 significantly increased diffusion coefficient (p<0.05) compared to hydrated rat skin. Lipid fluidization, lipid disruption structure and the irreversible denaturation of proteins in the SC layer of skin by isopropyl myristate, Tween 80 and plurololeique, as indicated by FT-IR and DSC, is the main factor for higher ERflux and ERD ratios compared to control.