title: A mechanistic study on the effect of ethanol and importance of water on permeation of drugs through human third-degree burn eschar.
abstract: Ethanol that affects hydration of skin and used in wound treatment formulations was studied here for its effect on permeation of drugs through burn eschar and to investigate the presence of a porous pathway in this barrier. In this study, permeations of clindamycin phosphate (CP, hydrophilic) and diazepam (lipophilic) through human burn eschar were investigated in the presence and absence of ethanol. Permeability coefficients (K(p) ) of CP and diazepam through hydrated eschar were calculated to be 13·1 × 10(-3)  and 17·4 × 10(-3)  cm/h respectively. These K(p)  values were decreased by about 1·5-5·3 and 2-10·7 times respectively upon the addition of 20-70% ethanol. Increased amount of ethanol decreased permeation flux of CP (2-20 times) and increased that of diazepam (3-80 times) from saturated solutions. Thermal analysis showed that ethanol dehydrates eschar and also changes its internal proteineous structure. Such changes were concluded to be the main reasons behind decreased K(p)  of both drugs. Comparison of K(p)  data suggests the possibility and importance of a pore pathway in permeation of both drugs through the hydrated burn eschar. Present results show that ethanol, and possibly other dehydrating agents, can decrease the permeability of eschar and that this effect should be considered in formulation developments.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Ghaffari
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Moghimi
authors.forename: Ali
authors.initials: A
authors.lastname: Manafi
authors.forename: Habibolah
authors.initials: H
authors.lastname: Hosseini
mesh_terms: D000328:Adult; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D002056:Burns / Q000378:metabolism*; D002152:Calorimetry, Differential Scanning; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D002981:Clindamycin / Q000031:analogs & derivatives; D003975:Diazepam / Q000737:chemistry; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010539:Permeability / Q000187:drug effects; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D013818:Thermogravimetry; D014867:Water / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000891:Anti-Infective Agents, Local; D014867:Water; D000431:Ethanol; D002981:Clindamycin; C007084:clindamycin phosphate; D003975:Diazepam