Liu C et al / Acta Pharmacol Sin 2002 Sep; 23 (9): 792-796

AIM: 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 ¡æ. 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× 10-6 cm·s-1 and 2.99 × 10-7cm·s-1, respectively. The total permeability coefficient increased with the fraction of unionized form. CONCLUSION: 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. INTRODUCTION The examination of penetration route for transbuccal drug delivery is important because it is fundamental to select the proper penetration enhancer to improve the drug permeability. Based on the cellular structure of the oral mucosa, there are two possible pathways for passive drug transportation the paracellular route and the transcellular route. The physicochemical properties of the diffusant determine the dominant route. For lipophilic compounds, the transcellular pathway is the main route. For hydrophilic compounds, paracellular transport is the primary route. The flux of drug through the membrane under sink condition for paracellular route can be written as[1]: