Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers

• Published in: Methods and findings in experimental and clinical pharmacology Vol. 30; no. 7; p. 499
• Main Authors: Shah, D K, Khandavilli, S, Panchagnula, R
• Format: Journal Article
• Language: English
• Published: Spain 01.09.2008
• Subjects: Administration, Cutaneous; Adrenergic Uptake Inhibitors - administration & dosage; Adrenergic Uptake Inhibitors - chemistry; Adrenergic Uptake Inhibitors - pharmacokinetics; Amides - chemistry; Animals; Epidermis - drug effects; Epidermis - metabolism; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Imipramine - administration & dosage; Imipramine - chemistry; Imipramine - pharmacokinetics; In Vitro Techniques; Lipids - chemistry; Permeability - drug effects; Pharmaceutical Vehicles - chemistry; Propylene Glycol - chemistry; Rats; Rats, Sprague-Dawley; Skin - drug effects; Skin - metabolism; Skin Absorption - drug effects; Skin Absorption - physiology; Spectroscopy, Fourier Transform Infrared - methods; Spectroscopy, Near-Infrared - methods; Thermogravimetry - methods; Water - chemistry; Water - metabolism; Water Loss, Insensible - drug effects; Water Loss, Insensible - physiology
• ISSN: 0379-0355
• DOI: 10.1358/mf.2008.30.7.1159653

Vehicles and permeation enhancers (PEs) used in transdermal drug delivery (TDD) of a drug can affect skin hydration, integrity and permeation of the solute administered. This investigation was designed to study the effect of the most commonly used vehicles and PEs on rat skin hydration, barrier function and permeation of an amphiphilic drug, imipramine hydrochloride (IMH). An array of well-established techniques were used to confirm the findings of the study. Thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy were used to determine changes in skin hydration. Alteration of the stratum corneum (SC) structure was investigated using FTIR studies. To monitor the barrier function alteration, transepidermal water loss (TEWL) measurement and permeation studies were performed. Our findings indicate that with hydration, there was an increase in the bound water content of the skin, and pseudoequilibrium of hydration (a drastic decrease in hydration rate) was achieved at around 12 h. Hydration increased the ratio between amide-I and amide-II peaks in FTIR and reduced the C-H stretching peak area. Both propylene glycol (PG) and ethanol (EtOH) dehydrated skin, with the latter showing a predominant effect. Furthermore, it was confirmed that PG and EtOH decreased the bound water content due to alteration in the protein domains and extraction of SC lipids, respectively. The effect of hydration on the SC was found to be similar to that reported for temperature. Permeation studies revealed that the dehydration caused by vehicles decreased IMH flux, whereas the flux was enhanced by PEs. The role of partition was predominant for the permeation of IMH through dehydrated skin. A synergistic effect was observed for PG and menthol in the enhancement of IMH. Further findings provided strong evidence that PG affects protein domains and EtOH extracts lipids from the bilayer. Both PG and EtOH, with or without PEs, increased TEWL. Initial TEWL was well correlated with the flux of IMH through the same skin. It was found that both PG and EtOH affect the permeation of solute and TEWL by dehydration. The experiments also proved that the initial TEWL value has a strong potential as a predictive tool for the permeation of the solute.