Cyclodextrins and chitosan derivatives in sublingual delivery of low solubility peptides: A study using cyclosporin A, α-cyclodextrin and quaternary chitosan N-betainate
| Autor: | Laura Matilainen, Seppo Auriola, Janne Mannila, Pekka Jarho, Jukka Holappa, Kristiina Järvinen |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Spectrometry Mass Electrospray Ionization alpha-Cyclodextrins Administration Sublingual Biological Availability Pharmaceutical Science Dosage form Chitosan Sublingual Absorption chemistry.chemical_compound Drug Delivery Systems Drug Stability Cyclosporin a Animals Solubility Chromatography High Pressure Liquid chemistry.chemical_classification Cyclodextrins Chromatography Cyclodextrin Bioavailability Betaine Cold Temperature chemistry Area Under Curve Drug delivery Cyclosporine Rabbits Peptides Algorithms Half-Life Nuclear chemistry |
| Zdroj: | International Journal of Pharmaceutics. 381:19-24 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2009.07.012 |
| Popis: | Systemic drug delivery through intraoral membranes may offer a promising administration route for lipophilic peptide drugs. The aim of the present study was to investigate the effect of alpha-cyclodextrin (alpha-CD) and a novel chitosan derivative, chitosan N-betainate (CH), on sublingual absorption of a hydrophobic model peptide cyclosporin A (CsA), and the effect of temperature on the complexation of CsA with alpha-CD. Complexation of CsA with alpha-CD was studied using the phase-solubility method. Sublingual absorption of CsA was studied by administration of solid CsA/alpha-CD complex (with and without CH solution), solid CsA/alpha-CD/CH formulation and solid plain CsA to rabbits. The solubility of CsA in aqueous alpha-CD solution (14%) increased with decreasing temperature; the solubility of CsA at room temperature, +5 and +1 degrees C was 1.2, 12 and 19mg/ml, respectively. The bioavailability of CsA after administration of plain CsA, solid CsA/alpha-CD and solid CsA/alpha-CD/CH (0.6+/-0.5, 1.4+/-0.7 and 1.7+/-0.8%, respectively; mean+/-S.D.) was further increased when solid CsA/alpha-CD was administered together with CH solution (3.2+/-2.2%). The present study shows that decreased temperature can be effectively utilized to produce CsA/alpha-CD complexes. It was also shown that alpha-CD and CH may be advantageous in sublingual delivery of lipophilic peptides, although the absolute bioavailability remains low. |
| Databáze: | OpenAIRE |
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