PURPOSE: To determine the major routes of buccal transport of lamotrigine and to examine the effects of pH on drug permeation. METHODS: Transbuccal permeation of lamotrigine across porcine buccal mucosa was studied by using in-line Franz type diffusion cell at 37 degrees C. The permeability of lamotrigine was determined at pH 4.0 to 9.0. The permeability of unionized (Pu) and ionized (Pi) species of drug were calculated by fitting the data to a mathematical model. Lamotrigine was quantified by using the HPLC method. RESULTS: The steady state flux increased linearly with increasing the donor concentration (r2 = 0.9639) at pH 7.4. The permeability coefficient and the partition coefficient of the drug increased with increasing the pH. The values of Pu and Pi were 0.7291 x 10(-5) cm/sec and 0.2500 x 10(-5) cm/sec, respectively. The observed permeability coefficients and the permeability coefficients calculated from mathematical model at various pH showed good linearity (r(2) = 0.9267). The total permeability coefficient increased with increasing the fraction of unionized form of the drug. CONCLUSION. Lamotrigine permeated through buccal mucosa by a passive diffusion process. The partition coefficient and pH dependency of drug permeability indicated that lamotrigine was transported mainly via the transcellular route by a partition mechanism.
PURPOSE: To determine the major routes of buccal transport of lamotrigine and to examine the effects of pH on drug permeation. METHODS: Transbuccal permeation of lamotrigine across porcine buccal mucosa was studied by using in-line Franz type diffusion cell at 37 degrees C. The permeability of lamotrigine was determined at pH 4.0 to 9.0. The permeability of unionized (Pu) and ionized (Pi) species of drug were calculated by fitting the data to a mathematical model. Lamotrigine was quantified by using the HPLC method. RESULTS: The steady state flux increased linearly with increasing the donor concentration (r2 = 0.9639) at pH 7.4. The permeability coefficient and the partition coefficient of the drug increased with increasing the pH. The values of Pu and Pi were 0.7291 x 10(-5) cm/sec and 0.2500 x 10(-5) cm/sec, respectively. The observed permeability coefficients and the permeability coefficients calculated from mathematical model at various pH showed good linearity (r(2) = 0.9267). The total permeability coefficient increased with increasing the fraction of unionized form of the drug. CONCLUSION. Lamotrigine permeated through buccal mucosa by a passive diffusion process. The partition coefficient and pH dependency of drug permeability indicated that lamotrigine was transported mainly via the transcellular route by a partition mechanism.