title: Azone® decreases the buccal mucosal permeation of diazepam in a concentration-dependent manner via a reservoir effect.
abstract: 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 (p < 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.
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
authors: Emil
authors: E
authors: Meng-Lund
authors: Jette
authors: J
authors: Jacobsen
authors: Liang
authors: L
authors: Jin
authors: Christian
authors: C
authors: Janfelt
authors: René
authors: R
authors: Holm
authors: Anette
authors: A
authors: Müllertz
authors: Joseph A
authors: JA
authors: Nicolazzo
mesh_terms: D000759:Adjuvants, Anesthesia / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000278:Administration, Buccal; D000818:Animals; D001381:Azepines / Q000378:metabolism*; D048271:Chitosan / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005782:Gels / Q000737:chemistry; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000378:metabolism*; D013552:Swine
chemical_list: D000759:Adjuvants, Anesthesia; D001381:Azepines; D005782:Gels; D014677:Pharmaceutical Vehicles; C035229:laurocapram; D048271:Chitosan; D003975:Diazepam
keywords: Azone®; absorption enhancer; buccal; chitosan; controlled release; diazepam; passive diffusion; permeability