In vitro permeation of tetramethylpyrazine across porcine buccal mucosa.
OBJECTIVE
To examine the in-vitro transport route of tetramethylpyrazine (TMP) across porcine buccal mucosa and to investigate the effects of drug concentration, pH in donor chamber, and 1-octanol/buffer partition coefficient on transbuccal permeation.


METHODS
In-vitro permeation of TMP through porcine buccal mucosa was studied by using in-line flow through diffusion cells at 37 . The permeability of TMP was evaluated at different donor pH and drug concentration. Permeability of unionized (Pu) and ionized TMP (Pi) was calculated by using the Scientist software.


RESULTS
The steady state flux of TMP increased linearly with the donor concentration (r2=0.96) at pH 7.4. The permeability and the partition coefficient increased with pH. Pu and Pi were 9.05 x 10(-6) cm.s(-1) and 2.99 x 10(-7) cm.s(-1), respectively. The total permeability coefficient increased with the fraction of unionized form.


CONCLUSIONS
TMP permeated through buccal mucosa by a passive diffusion process. The partition coefficient and pH dependency of drug permeability indicated that the drug was transported mainly via the transcellular route by a partition mechanism.
Liu
Chen
C
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China. liuchen_lc@263.net.
Xu
Hui-Nan
HN
Li
Xiao-Ling
XL
D000042:Absorption; D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D009061:Mouth Mucosa / Q000378:metabolism*; D011719:Pyrazines / Q000493:pharmacokinetics*; D013552:Swine
D000318:Adrenergic beta-Agonists; D011719:Pyrazines; C017953:tetramethylpyrazine