title: Formulation of carbenoxolone for delivery to the skin.
abstract: Carbenoxolone (CEX), a semi-synthetic derivative of glycyrrhetinic acid, has previously been used as a disodium salt for the management of dyspepsia and peptic ulcer because of its anti-inflammatory properties. Although glycyrrhetinic acid is available in pharmaceutical and personal care products for skin care, the topical use of the free acid form of CEX, has not previously been reported. In this work we investigated the percutaneous penetration of CEX. Solubility and permeability studies were conducted using a range of solvents or skin permeation enhancers (SPEs) commonly used for skin delivery. Binary combinations of dimethyl isosorbide (DMI) and Transcutol™ (TC) with isopropyl myristate (IPM) were effective in promoting skin permeation of CEX although individual solvents were not. Alternative fatty acid esters to IPM were subsequently investigated with the most promising formulation consisting of TC and propylene glycol laurate (PGL). Interestingly, propylene glycol monolaurate (PGML) did not demonstrate comparable efficacy when combined with TC. A ternary formulation consisting of TC, PGL and IPM demonstrated the best permeation enhancement of CEX compared with all other vehicles. The findings confirm (i) the feasibility of promoting CEX penetration across the skin (ii) the synergistic effect of combinations of solvents and SPEs on dermal and transdermal delivery (iii) the necessity for more fundamental studies to explain the differential effects of fatty acid esters on the skin barrier.
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hirata
authors.forename: Fouad
authors.initials: F
authors.lastname: Helal
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hadgraft
authors.forename: Majella E
authors.initials: ME
authors.lastname: Lane
mesh_terms: D000279:Administration, Cutaneous; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002229:Carbenoxolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006801:Humans; D010539:Permeability; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D012997:Solvents / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D005079:Excipients; D012997:Solvents; D002229:Carbenoxolone