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. 2007 Jul 13;8(3):E28–E33. doi: 10.1208/pt0803055

Transbuccal delivery of 5-Aza-2′-deoxycytidine: Effects of drug concentration, buffer solution, and bile salts on permeation

Ravichandran Mahalingam 1,✉, Harish Ravivarapu 2, Sanjeev Redkar 2, Xiaoling Li 1, Bhaskara R Jasti 1,✉
PMCID: PMC2750551  PMID: 17915805

Abstract

Delivery of 5-aza-2′-deoxycytidine (decitabine) across porcine buccal mucosa was evaluated as an alternative to the complex intravenous infusion regimen currently used to administer the drug. A reproducible high-performance liquid chromatography method was developed and optimized for the quantitative determination of this drug. Decitabine showed a concentration-dependent passive diffusion process across porcine buccal mucosa. An increase in the ionic strength of the phosphate buffer from 100 to 400 mM decreased the flux from 3.57±0.65 to 1.89±0.61 μg/h/cm2. Trihydroxy bile salts significantly enhanced the flux of decitabine at a 100 mM concentration (P>.05). The steady-state flux of decitabine in the presence of 100 mM of sodium taurocholate and sodium glycocholate was 52.65±9.48 and 85.22±7.61 μg/cm2/h, respectively. Two dihydroxy bile salts, sodium deoxytaurocholate and sodium deoxyglycocholate, showed better enhancement effect than did trihydroxy bile salts. A 38-fold enhancement in flux was achieved with 10 mM of sodium deoxyglycocholate.

Keywords: Decitabine, transmucosal, buccal, ionic strength, bile salts

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