title: Drug permeation through skin is inversely correlated with carrier gel rigidity.
abstract: Controlled release plays an essential role in formulating topical and transdermal drug delivery systems. In this study, we correlated the skin permeation of Sesamin, a lipophilic drug, with the rheological properties of two different organogel carriers, i.e., low molecular weight gelling agent N-lauroyl-l-glutamic acid di-n-butylamide (GP-1) and Carbopol polymeric gels. Although these two gels have distinct network structures, they share the same trend: the more rigid the gel network and the higher the gelator concentration, the lower the steady flux of Sesamin through skin. This negative correlation lies in the fact that organogel network hinders the diffusion of drug to the gel-skin interface; as a result, the depletion zone near the interface is non-negligible and contributes to the resistance of the whole diffusion system, and thus, the permeation flux is reduced. More interestingly, the dependence of the steady flux against gel complex modulus at the linear viscoelastic region followed a "universal" power law regardless of the gel types, i.e., 1/J = 1/J0 + a(G*)(ε)/C0 with a = 11.25, ε = 0.21 ± 0.03 for GP-1 gels, and a = 0.16, ε = 1.05 ± 0.06 for Carbopol gels, J0 is the steady flux without gel (G* = 0), and C0 is the initial concentration of drug in gels. The empirical formulae are crucial in developing transdermal organogel systems with controlled release of drug content through readily obtainable data of their rheological properties. The explanation for the power law dependence of the steady flux on gel complex modulus is discussed.
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS) , #05-01, 28 Medical Drive, 117456, Singapore.
authors.forename: Duc-Viet
authors.initials: DV
authors.lastname: Nguyen
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Hairui
authors.initials: H
authors.lastname: Li
authors.forename: Bin Sheng
authors.initials: BS
authors.lastname: Wong
authors.forename: Chang Yee
authors.initials: CY
authors.lastname: Low
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Liu
authors.forename: Lifeng
authors.initials: L
authors.lastname: Kang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D005782:Gels / Q000737:chemistry*; D051381:Rats; D012212:Rheology; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D004337:Drug Carriers; D005782:Gels
keywords: Sesamin; Stokes−Einstein relation; diffusion in organogel; low-molecular-weight gelator; organogel; polymeric gelator; rheological property; skin permeation