Buccal delivery of metformin: TR146 cell culture model evaluating the use of bioadhesive chitosan discs for drug permeability enhancement
Abstract
The oral cavity is considered an attractive site of drug administration. Metformin is currently, used in oral diabetes treatment. The aim of the current study was to study the feasibility of metformin, to permeate the buccal epithelium applying a bioadhesive and permeation enhancing drug delivery system. The in vitro TR146 cell culture model was used to study the effect of drug concentration (5-100mM) and the impact of a bioadhesive chitosan formulation (discs) and chitosan in solution (0-20mg/mL) acting as a permeation enhancer. The permeation of metformin occurred by passive diffusion via the paracellular pathway driven by the concentration gradient, yet with a possibility of increasing the metformin transport by using higher, donor concentrations. When using floating baskets, as a new application of the TR146 cell culture model, it was possible to observe a time-dependent effect of the bioadhesive metformin discs and, metformin permeation may be increased due to a combination of bioadhesion and permeation enhancement induced by chitosan, although the permeation enhancing effect of chitosan was not statistically significant. The limited apparent buccal permeability of metformin observed in vitro, suggest that in vivo absorption of therapeutic doses of metformin needs to take place as a combination of buccal and intestinal absorption as metformin therapy requires the use of high doses.
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