Transbuccal delivery of 5-aza-2 -deoxycytidine: effects of drug concentration, buffer solution, and bile salts on permeation.
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 microg/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 microg/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.
Mahalingam
Ravichandran
R
T. J. Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA.
Ravivarapu
Harish
H
Redkar
Sanjeev
S
Li
Xiaoling
X
Jasti
Bhaskara R
BR
D000818:Animals; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002021:Buffers; D002610:Cheek; D002851:Chromatography, High Pressure Liquid; D000077209:Decitabine; D009061:Mouth Mucosa / Q000378:metabolism*; D009994:Osmolar Concentration; D010539:Permeability; D013552:Swine
D001647:Bile Acids and Salts; D002021:Buffers; D000077209:Decitabine; D001374:Azacitidine