Enhanced in vitro transbuccal drug delivery of ondansetron HCl

Abstract

The effect of chemical enhancers and iontophoresis on the in vitro transbuccal delivery of 0.5% ondansetron HCl (ODAN HCl) was investigated using porcine buccal tissue. The chemical enhancers used were dodecyl 2-(N,N-dimethyl amino) propionate (DDAIP), its HCl salt dodecyl-2-(N,N-dimethylamino) propionate hydrochloride (DDAIP HCl), N-(4-bromobenzoyl)-S,S-dimethyliminosulfurane (Br-iminosulfurane), and azone. This study demonstrated that anodal iontophoresis at 0.1, 0.2 and 0.3 mA current intensity significantly increased transbuccal delivery of ODAN HCl 3.3-fold, 5.2-fold and 7.1-fold respectively, compared to control. DDAIP HCl provided significantly higher transbuccal delivery of ODAN HCl than did DDAIP, azone and Br-iminosulfurane. It was found that DDAIP HCl in water significantly enhanced drug permeability (920 μg/cm(2)) compared to DDAIP HCl in propylene glycol (PG) (490 μg/cm(2)) during 24h. It was also found that 5% (w/v) DDAIP HCl in water alone provided higher permeation flux (29.3 μg/cm(2)/h) than iontophoresis alone at 0.3 mA (22.8 μg/cm(2)/h) during the same 8h treatment. A light microscopy study showed that treatment with chemical enhancers and iontophoresis did not cause major morphological changes in the buccal tissue. EpiOral™ MTS cytotoxicity studies demonstrated that DDAIP HCl at less than 5% (w/v) in water did not have significant detrimental effects on the cells.