Enhanced in vitro transbuccal drug delivery of ondansetron HCl.
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.
Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, NJ 08854, United States.
Longsheng
L
Hu
Bassam B
BB
Damaj
Richard
R
Martin
Bozena B
BB
Michniak-Kohn
D000042:Absorption; D000278:Administration, Buccal; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001381:Azepines / Q000494:pharmacology* / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D066298:In Vitro Techniques; D007478:Iontophoresis; D007700:Kinetics; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D017294:Ondansetron / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D013457:Sulfur Compounds / Q000494:pharmacology* / Q000633:toxicity; D013678:Technology, Pharmaceutical / Q000379:methods
D001381:Azepines; C119492:N-(4-bromobenzoyl)-S,S-dimethyliminosulfurane; D013457:Sulfur Compounds; C035229:laurocapram; D017294:Ondansetron; C085388:dodecyl 2-(N,N-dimethylamino)propionate; D000409:Alanine