Effect of Permeation Enhancers on the Buccal Permeability of Nicotine: Ex vivo Transport Studies Complemented by MALDI MS Imaging.

Abstract:

PURPOSE:The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. METHODS:The impact of sodium taurodeoxycholate (STDC), sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone® on the permeability of [3H]-nicotine and [14C]-mannitol (a paracellular marker) across porcine buccal mucosa was studied ex vivo in modified Ussing chambers. The distribution of nicotine, mannitol and permeation enhancers was imaged using using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). RESULTS:Despite STDC significantly increasing permeability of [14C]-mannitol, no enhancing effect was seen on [3H]-nicotine permeability with any of the permeation enhancers. Rather, SDS and DMSO retarded nicotine permeability, likely due to nicotine being retained in the donor compartment. The permeability results were complemented by the spatial distribution of nicotine and mannitol determined with MALDI MSI. CONCLUSIONS:The buccal permeability of nicotine was affected in an enhancer specific manner, suggesting that nicotine primarily diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo permeability studies and to be a useful qualitative tool for visualizing drug and penetration enhancer distribution in buccal mucosa.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Marxen E,Jin L,Jacobsen J,Janfelt C,Hyrup B,Nicolazzo JA

doi

10.1007/s11095-017-2332-y

subject

Has Abstract

pub_date

2018-02-21 00:00:00

pages

70

issue

3

eissn

0724-8741

issn

1573-904X

pii

10.1007/s11095-017-2332-y

journal_volume

35

pub_type

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