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.

A Mechanistic Study on the Fluidization and Enhancement Effects of Cineole Toward Stratum Corneum Intercellular Lamellar Lipids: A Liquid Crystalline Model Approach

“…The run time was 16 min, and the retention time of diazepam was around 14 min. Drug standards were prepared in the mobile phase and detected at a wavelength of 254 nm ( 26 ).…”

Current status and future outlook of nano‐based systems for burn wound management

“…The main advantage of these systems includes delivering medicine to the desired location, sustaining long-term release of drugs, reducing drug toxicity and side effects caused by massive drug release during conventional administration. Among these systems, liposomes are the most widely used for wound therapy (Ghaffari, Manafi, & Moghimi, 2015;Low, Martin, Hill, & Kenward, 2013). In one study, the effects of liposome polyvinyl-pyrrolidone-iodine (PVP-I) hydrogel on the healing of partial-thickness burn wounds, showed more rapid epithelialization and shorter time to complete healing than management with silversulfadiazine cream.…”

“…On the other hand, ethical consideration in animal use for research purposes has led international regulations to limit the use of animals for the mentioned purposes. In ex vivo models, skin or tissue explant takes from animal or human skin and place in a defined culture medium or apparatus (such as static diffusion cell systems) (Ghaffari, Manafi, & Moghimi, 2013;Moghimi, Makhmalzadeh, & Manafi, 2009). Partial-thickness and full-thickness ex vivo systems including epidermis, upper part of the dermis and dermis employed in many studies related to human dermatology for functional study of various case such as, tensile strength of skin wound healing, epithelialization, infection, expression of cytokines and growth factor (EGF) in wound healing process (Mendoza-Garcia, Sebastian, Alonso- , & Bayat, 2015).…”

“…So far, several studies have been carried out on various lipidbased Nano-systems in terms of composition, size, and shape, as well as various loaded factors for different purposes (Table 1). Among these systems, deformable systems such as ethosomal and transfersomal systems are used for drug delivery through healthy or damaged skin (Ghaffari et al, 2012), and fewer studies have been conducted for evaluation of these systems for drug delivery to wounds. However, for other systems, despite the high potential of these systems, conducted studies for drug delivery to the wound are also less.…”