title: The effects of polar excipients transcutol and dexpanthenol on molecular mobility, permeability, and electrical impedance of the skin barrier.
abstract: In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid-state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol.
authors.affiliation: Department of Biomedical Science, Faculty of Health and Society, Malmö University, SE-205 06 Malmö, Sweden; Biofilms Research Center for Biointerfaces, Malmö University, SE-205 06 Malmö, Sweden. Electronic address: sebastianbjorklund@gmail.com.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Björklund
authors.affiliation: Physical Chemistry, The Center for Chemistry and Chemical Engineering, Lund University, Box 124, SE-221 00 Lund, Sweden.
authors.forename: Quoc Dat
authors.initials: QD
authors.lastname: Pham
authors.affiliation: LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
authors.forename: Louise Bastholm
authors.initials: LB
authors.lastname: Jensen
authors.affiliation: LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
authors.forename: Nina Østergaard
authors.initials: NØ
authors.lastname: Knudsen
authors.affiliation: LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
authors.forename: Lars Dencker
authors.initials: LD
authors.lastname: Nielsen
authors.affiliation: LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
authors.forename: Katarina
authors.initials: K
authors.lastname: Ekelund
authors.affiliation: Department of Biomedical Science, Faculty of Health and Society, Malmö University, SE-205 06 Malmö, Sweden; Biofilms Research Center for Biointerfaces, Malmö University, SE-205 06 Malmö, Sweden.
authors.forename: Tautgirdas
authors.initials: T
authors.lastname: Ruzgas
authors.affiliation: Department of Biomedical Science, Faculty of Health and Society, Malmö University, SE-205 06 Malmö, Sweden; Biofilms Research Center for Biointerfaces, Malmö University, SE-205 06 Malmö, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Engblom
authors.affiliation: Physical Chemistry, The Center for Chemistry and Chemical Engineering, Lund University, Box 124, SE-221 00 Lund, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Sparr
mesh_terms: D000818:Animals; D017097:Electric Impedance; D005026:Ethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D005712:Galvanic Skin Response / Q000187:drug effects*; D010205:Pantothenic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013552:Swine
chemical_list: D005026:Ethylene Glycols; D010205:Pantothenic Acid; C007288:dexpanthenol; C010111:carbitol
keywords: Excipients; Molecular mobility; Skin permeability; Steady-state flux; Stratum corneum; Topical drug delivery