Azone® Decreases the Buccal Mucosal Permeation of Diazepam in a Concentration‐Dependent Manner via a Reservoir Effect. Issue 4 (15th February 2014)

• Record Type: Journal Article
• Authors: Meng‐Lund, Emil; Jacobsen, Jette; Jin, Liang; Janfelt, Christian; Holm, René; Müllertz, Anette; Nicolazzo, Joseph A.
• Is Part Of: Journal of pharmaceutical sciences. Volume 103:Issue 4(2014:Apr.)
• Page Start: 1133
• Page End: 1141
• Publication Date: 2014-02-15
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23877
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The purpose of this study was to examine concentration‐dependent effects of Azone® (AZ) on the buccal absorption of diazepam (DIAZ). Porcine buccal mucosa was placed in modified Ussing chambers and pretreated with 10 μL of 0%, 5%, 20%, and 50% (w/v) AZ in ethanol. DIAZ was administered to the donor chamber either in solution or a chitosan‐based gel. The donor chamber disappearance, receptor chamber appearance, and tissue retention of DIAZ were monitored over 2 h by HPLC, with AZ tissue disposition also measured by liquid chromatography–mass spectrometry profiling of tissue cryosections. DIAZ steady‐state flux values significantly (<italic>p</italic> < 0.05) decreased 1.4‐ and 2.4‐fold in 20% and 50% AZ‐pretreated tissues, respectively. Only 20% and 50% AZ‐pretreated tissues were also accompanied by an increased loss of DIAZ from the donor chamber, suggesting DIAZ was forming a reservoir in the buccal mucosa with higher AZ concentrations. Indeed, the percentage of the initial DIAZ dose remaining in the mucosa following a 2 h experiment was increased 3.0‐fold with a 50% AZ pretreatment compared with control. AZ provided a concentration‐dependent reservoir for DIAZ in buccal mucosa, resulting in retarded release into the receptor chamber, an approach that may be exploited for controlled release of DIAZ. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1133–1141, 2014</p> </abstract>