In vitro evaluation of natural and methylated cyclodextrins as buccal permeation enhancing system for omeprazole delivery

Abstract

Omeprazole Permeation Stability a b s t r a c tIn 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 b-and methyl-b-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 b-cyclodextrin and methyl-b-cyclodextrin, respectively. The presence of L-arginine increases drug permeation 1.4-fold in omeprazole complexed with b-cyclodextrin and 2.4-fold in the inclusion complex formed with methyl-b-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.

Poloxamer 407 microspheres for orotransmucosal drug delivery. Part II: In vitro/in vivo evaluation

“…The use of penetration enhancers is a logical approach to increase the drug permeation across the epithelium. The effect of many classes of penetration enhancers such as surfactants and bile salts, fatty acids, ethanol (Nicolazzo et al, 2005;Burgalassi et al, 2006), cyclodextrin derivatives (Figueiras et al, 2009) or chitosan derivatives (Sandri et al, 2004a) has been studied. To provide a better retention of the dosage form in the site of application, bioadhesive polymers have been used extensively in buccal drug delivery systems (Burgalassi et al, 1996;Shojaei et al, 2000;Kockisch et al, 2003;Sandri et al, 2004b), hence the mucoadhesion/enhancer combination can lengthen the residence time and improve the drug bioavailability.…”

Development of bioadhesive buccal tablets for felodipine and pioglitazone in combined dosage form: In vitro, ex vivo, and in vivo characterization

“…Addition of HPβCD to the matrix increased the flux by increasing the solubility of FDP and PIO, thus improving the diffusible form of the drug species at the tablet membrane interface. Cyclodextrins have been suggested to act as penetration enhancers (Figueiras et al, 2009). They enhance the drug permeation by carrying the actives through the aqueous barrier towards the surface of the membrane, where the drug passes from the complex into the membrane.…”

Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

“…Conventional formulation approaches for water-solubility enhancement include co-grinding with surfactants, 8,9 formation of solid dispersions, 10,11 and inclusion complexes with hydrophilic cyclodextrins. [12][13][14][15] In addition to these techniques, particle size reduction to the nanometer range has also been utilized. [16][17][18] For instance, the use of a nanosuspension was able to overcome the low/erratic absorption problem associated with poorly water-soluble drugs after peroral, 19,20 transdermal, 21 ocular, or pulmonary 23 administration.…”