Effect of Bile Salts on Transbuccal Permeability of Carbamazepine through Porcine Buccal Mucosa

Abstract

The delivery of drug through buccal mucosa provides potential advantages like prevention of enzymatic degradation in gastro intestinal tract and bypassing hepatic first-pass metabolism. However the significant aspect in transbuccal drug delivery is the very restrictive passage of drug through the buccal mucosa. In our earlier work we confirmed the ability of Carbamazepine (CBZ) to permeate through the porcine buccal mucosa. Our earlier study proved that CBZ crosses the membrane by passive diffusion. But the measured Flux (J s ) and permeation coefficient (K p ) of CBZ was s p insufficient to achieve plasma therapeutic concentration. In this study an approach was made to improve permeability of CBZ using some bile salts as chemical permeation enhancers like sodium taurocholate (STC) and sodium taurodeoxycholate (STDC) which are capable to lessening the barrier property of the mucosal tissue. These patches were subjected to ex vivo permeation studies. The six buccal patches of CBZ selected from our earlier reported formulations were subjected to this permeability improvement study. These patches were either based on HPMC K15M or Carbopol 934p or Chitosan in combination of PVA or PVP K30 or Sodium alginate. The significant change in J s and K p of formulations in presence and absence of chemical permeation enhancers STC or STDC (in two different p concentrations 0.1% and 0.5 % w/w) was evaluated by ex vivo permeation studies through porcine buccal mucosa under modified Franz diffusion cell. The calculated value of Flux (J s ) and Permeation coefficient (K p ) confirmed that s there was a significant increase in permeated amount of CBZ after the inclusion of permeation enhancers. The compatibility of bile salts with buccal mucosa was examined by histological studies and kinetic studies.