In vitro percutaneous absorption enhancement of propranolol hydrochloride through porcine epidermis by terpenes/ethanol.
The purpose of this study was to investigate the mechanism(s) of percutaneous absorption enhancement of propranolol hydrochloride (PHCL) across porcine epidermis by terpenes (e.g. menthone and limonene) in combination with ethanol. The in vitro percutaneous absorption experiments were performed using Franz diffusion cells. The solubility of PHCL in control and enhancer solutions was determined through high-performance liquid chromatography. Partitioning of PHCL to powdered SC from control or enhancer solutions was also determined in order to investigate the binding of PHCL to the SC from the SC/enhancer system. Fourier transform infrared spectroscopy (FT-IR) was employed to study the biophysical changes in stratum corneum (SC) lipids. The in vitro macroscopic barrier properties were investigated by measuring transepidermal water loss (TEWL) using Tewameter. Five percent menthone or limonene in combination with ethanol (EtOH) (menthone/EtOH or limonene/EtOH) significantly increased (P<0.05) the flux of PHCL through porcine epidermis in comparison to the control (EtOH). The partitioning of PHCL to the SC from the SC/enhancer system was also significantly greater than the SC/control system. The above enhancers showed a decrease in the peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison with the untreated SC, indicating the SC lipids extraction. Menthone/EtOH and limonene/EtOH enhanced (P<0.05) the in vitro TEWL through the epidermis in comparison to the control. Thus, an enhancement in the flux of PHCL by menthone/EtOH and limonene/EtOH is due to SC lipid extraction, macroscopic barrier perturbation, and improvement in the partitioning of the drug to the SC.
Zhao
K
K
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.
Singh
J
J
D000818:Animals; D053138:Cyclohexenes; D004058:Diffusion; D004347:Drug Interactions; D004431:Ear, External / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D000077222:Limonene; D008610:Menthol; D011433:Propranolol / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013552:Swine; D013729:Terpenes / Q000494:pharmacology*; D013997:Time Factors; D014867:Water / Q000378:metabolism
D053138:Cyclohexenes; D013729:Terpenes; D014867:Water; D008610:Menthol; D000431:Ethanol; D000077222:Limonene; C019466:menthone; D011433:Propranolol