title: In vitro evaluation of natural and methylated cyclodextrins as buccal permeation enhancing system for omeprazole delivery.
abstract: In this work the enhancing effect of cyclodextrins on the buccal permeation of a hydrophobic model drug, omeprazole was studied. First, the influence of the complexation with cyclodextrins in the absence and in the presence of an alkali agent, L-arginine, on the drug stability was checked at neutral conditions since omeprazole alone is only stable in basic conditions. In vitro transbuccal permeation of omeprazole non-complexed and complexed with beta- and methyl-beta-cyclodextrin and in presence of L-arginine was examined using freshly obtained porcine buccal mucosa. Tissue viability after incubation with sample solutions was assessed using a MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) biochemical assay and histological evaluation. The toxicity of the sample solutions on buccal mucosa was evaluated by measuring lactate dehydrogenase activity. The present results show that complexation with cyclodextrins increases drug stability at neutral conditions; furthermore, L-arginine contributed to higher drug stability. Permeation studies indicate an increase on drug permeation in complexed form of 1.1- and 1.7-fold for beta-cyclodextrin and methyl-beta-cyclodextrin, respectively. The presence of L-arginine increases drug permeation 1.4-fold in omeprazole complexed with beta-cyclodextrin and 2.4-fold in the inclusion complex formed with methyl-beta-cyclodextrin. The cell viability of the buccal mucosa after a 3 h incubation period, with all sample solutions, remained around 70% and lactate dehydrogenase assay showed that studied cyclodextrins, even in the presence of an alkali agent are not cytotoxic for porcine buccal mucosa. Histological evaluation of the tissue demonstrated that the buccal epithelium remains viable after 3 h of incubation with sample solutions.
authors.affiliation: Department of Pharmaceutical Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Figueiras
authors.forename: Juliane
authors.initials: J
authors.lastname: Hombach
authors.forename: Francisco
authors.initials: F
authors.lastname: Veiga
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D001120:Arginine / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D010539:Permeability; D013552:Swine; D013997:Time Factors; D018675:Toxicity Tests; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000897:Anti-Ulcer Agents; D004337:Drug Carriers; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D001120:Arginine; D007770:L-Lactate Dehydrogenase; C031215:betadex; D009853:Omeprazole