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Modification of buccal drug delivery following pretreatment with skin penetration enhancers.

The effect of the lipophilic skin penetration enhancers octisalate (OS), padimate O (PO), and Azone (AZ) on in vitro buccal permeability was assessed using caffeine (CAF), estradiol (E2), and triamcinolone acetonide (TAC) as model permeants. Buccal permeability was assessed in modified Ussing chambers, through both untreated porcine buccal mucosa and mucosa pretreated with an enhancer (5% w/v in 95% v/v ethanol) or ethanol alone. To ensure sink conditions were present, E2 permeability experiments were also performed with bovine serum albumin (BSA) 4% in the receptor solution. Mucosa-buffer partition studies were performed to determine the effect of enhancer pretreatment on the log mucosa-buffer partition coefficient (logK) of E2 and TAC. CAF permeability was only increased following pretreatment with ethanol 95%. E2 buccal transport was not altered following OS pretreatment, but was reduced by 26.3% with PO pretreatment and 67.6% with AZ pretreatment. Similar results were obtained with BSA 4% in the receptor solution. The logK of E2 was increased 1.4-fold and 2.2-fold in PO- and AZ-pretreated tissues, respectively, suggesting that the reduction in flux caused by PO and AZ may have been due to enhanced E2 tissue retention. The effect of OS and PO on TAC permeability was no different to that of ethanol. However, AZ enhanced TAC permeability 4.1-fold and this was accompanied by a 2.4-fold increase in the logK of TAC.