title: Influence of lidocaine hydrochloride and penetration enhancers on the barrier function of human skin.
abstract: Skin penetration enhancers (SPEs) are commonly employed in pharmaceutical and personal care products. These compounds transiently alter the barrier properties of the skin and we have previously investigated the effects of specific SPEs on skin barrier function in vivo. In the present study the effects of incorporation of an active pharmaceutical ingredient (API), lidocaine hydrochloride (LID HCl) in the SPEs previously studied were investigated. Solutions of LID HCl were prepared and applied to the volar forearm of human subjects with occlusion for 24h. Subsequently, tape stripping and trans epidermal water loss (TEWL) measurements were conducted for treated and control sites. The activities of the desquamatory proteases, kallikrein 5 (KLK 5) and kallikrein 7 (KLK 7) and API content were also measured from the tape strips. The propylene glycol (PG) formulation increased TEWL significantly (p<0.05) compared with the other SPEs and a mixture of the SPEs. However, only the isopropyl myristate (IPM) solution altered protease activity with a significant observed increase in kallikrein 5 (KLK 5). Incorporation of LID HCl appeared to ameliorate the effects of some of the SPEs on TEWL measurements compared with our previous study. Overall uptake of LID HCl into skin from the various formulations correlated very well with changes in TEWL. The findings should have implications for the choice of SPEs in topical and transdermal formulations, particularly where the skin barrier function of patients is already impaired for example in atopic eczema or psoriasis.
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1 N 1AX, England, UK.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1 N 1AX, England, UK.
authors.forename: Diar
authors.initials: D
authors.lastname: Mohammed
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1 N 1AX, England, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hadgraft
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1 N 1AX, England, UK. Electronic address: majella.lane@btinternet.com.
authors.forename: Majella E
authors.initials: ME
authors.lastname: Lane
mesh_terms: D000279:Administration, Cutaneous; D005026:Ethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D007848:Laurates / Q000737:chemistry / Q000494:pharmacology; D008012:Lidocaine / Q000737:chemistry / Q000494:pharmacology*; D009226:Myristates / Q000737:chemistry / Q000494:pharmacology; D011409:Propylene Glycols / Q000737:chemistry / Q000494:pharmacology; D057057:Serine Proteases / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*
chemical_list: D005026:Ethylene Glycols; D005079:Excipients; D007848:Laurates; D009226:Myristates; D011409:Propylene Glycols; C008205:isopropyl myristate; C098387:propyleneglycol monolaurate; D008012:Lidocaine; C010111:carbitol; D057057:Serine Proteases; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins
keywords: Lidocaine hydrochloride; Proteases; Skin penetration enhancers; Trans epidermal water loss