TRANSBUCCAL DELIVERY OF ACYCLOVIR - I - IN-VITRO DETERMINATION OF ROUTES OF BUCCAL TRANSPORT

Purpose. To determine the major routes of buccal transport of acyclovi r and to examine the effects of pH and permeation enhancer on drug per meation. Methods. Permeation of acyclovir across porcine buccal mucosa was studied by using side-by-side flow through diffusion cells at 37 degrees C. The permeability of acyclovir was determined at pH range of 3.3 to 8.8. Permeability of different ionic species was calculated by fitting the permeation data to a mathematical model. Acyclovir was qu antified using HPLC. Results, Higher steady state fluxes were observed at pH 3.3 and 8.8. The partition coefficient (1-octanol/buffer) and t he solubility of acyclovir showed the same pH dependent profile as tha t of drug permeation. In the presence of sodium glycocholate (NaGC) (2 -100 mM), the permeability of acyclovir across buccal mucosa was incre ased 2 to 9 times. This enhancement was independent of pH and reached a plateau above the critical micelle concentration of NaGC. The permea bilities of anionic, cationic. and zwitterionic species were 3.83 x 10 (-5), 4.33 x 10(-5), and 6.24 x 10(-6) cm/sec, respectively. Conclusio ns. The in vitro permeability of acyclovir across porcine buccal mucos a and the octanol-water partitioning of the drug were pH dependent. A model of the paracellular permeation of the anionic, cationic, and zwi tterionic forms of acyclovir is consistent with these data. The parace llular route was the primary route of buccal transport of acyclovir, a nd the enhancement of transbuccal transport of acyclovir by sodium gly cocholate (NaGC) appeared to operate via this paracellular route.