Effects of permeation enhancers on flufenamic acid delivery in Ex vivo human skin by confocal Raman microscopy
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- 作者：Yelena Pyatski ; Qihong Zhang ; Richard Mendelsohn ; Carol R. Flach ; flach@andromeda.rutgers.edu" class="auth_mail" title="E-mail the corresponding author
- 关键词：SC ; stratum corneum ; FluA ; flufenamic acid ; CPE ; chemical penetration enhancer ; Et-d ; ethanol-D6 ; Oct-d ; n-octyl-d17-alcohol ; PG-d ; 1 ; 2-propanediol-D6 ; VE ; viable epidermis ; NMF ; natural moisturizing factor
- 刊名：International Journal of Pharmaceutics
- 出版年：2016
- 出版时间：30 May 2016
- 年：2016
- 卷：505
- 期：1-2
- 页码：319-328
- 全文大小：3012 K
文摘
For effective topical delivery, a drug must cross the stratum corneum (SC) barrier into viable tissue. The use of permeation enhancers is a widespread approach for barrier modification. In the current study, flufenamic acid (FluA), a non-steroidal anti-inflammatory drug, is a model agent for investigating the influence of hydrophobic versus hydrophilic enhancers. In separate experiments, FluA in octanol or propylene glycol/ethanol (75/25) is applied to the SC for varying times followed by confocal Raman microscopic mapping of drug and enhancer penetration and spatial distribution. Deuterated versions of the enhancers permit us to spectroscopically distinguish the exogenous chemicals from the endogenous SC lipids without affecting penetration parameters. The FluA pathway is tracked by the C
C stretching mode at ∼1618 cm−1. Discrete, small inclusions of both enhancers are observed throughout the SC. High concentrations of FluA are co-localized with octanol domains which appear to provide a pathway to the viable epidermis for the drug. In contrast, FluA concentrates in the upper SC when using the hydrophilic agent and endogenous lipids appear unperturbed in regions outside the enhancer pockets. The ability to examine perturbations to endogenous ultrastructure and molecular structure in skin while tracking penetration pathways provides insight into delivery mechanisms.
C stretching mode at ∼1618 cm−1. Discrete, small inclusions of both enhancers are observed throughout the SC. High concentrations of FluA are co-localized with octanol domains which appear to provide a pathway to the viable epidermis for the drug. In contrast, FluA concentrates in the upper SC when using the hydrophilic agent and endogenous lipids appear unperturbed in regions outside the enhancer pockets. The ability to examine perturbations to endogenous ultrastructure and molecular structure in skin while tracking penetration pathways provides insight into delivery mechanisms.