The Effect of Cyclodextrins on Chemical and Physical Stability of Glucagon and Characterization of Glucagon/γ-CD Inclusion Complexes
| Autor: | Pekka Keski-Rahkonen, Kim Lambertsen Larsen, Tomi Järvinen, Laura Matilainen, Pekka Jarho, Seppo Auriola, Reinhard Wimmer |
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| Rok vydání: | 2008 |
| Předmět: |
chemistry.chemical_classification
Magnetic Resonance Spectroscopy Cyclodextrin Viscosity Molecular Sequence Data Pharmaceutical Science Nuclear magnetic resonance spectroscopy Hydrogen-Ion Concentration Glucagon Inclusion compound Excipients chemistry.chemical_compound Drug Stability chemistry Ionic strength Molecule Organic chemistry Chemical stability Amino Acid Sequence Chromatography High Pressure Liquid Pancreatic hormone gamma-Cyclodextrins Nuclear chemistry |
| Zdroj: | Matilainen, L, Larsen, K L, Wimmer, R, Keski-Rahkonen, P, Auriola, S, Järvinen, T & Jarho, P 2008, ' The effect of cyclodextrins on chemical and physical stability of glucagon and characterization of glucagon/gamma-CD inclusion complexes : ', Journal of Pharmaceutical Sciences, vol. 97, no. 7, pp. 2720-2729 . https://doi.org/10.1002/jps.21209 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.21209 |
| Popis: | The purpose of the study was to evaluate the effect of cyclodextrin (CD) complexation on the chemical and physical stability of a polypeptide hormone glucagon and to study the interactions between glucagon and gamma-cyclodextrin molecules in inclusion complexes. The chemical stability of glucagon at pH 2.0 was studied with HPLC-UV and HPLC-MS/MS. The physical stability of glucagon at pH 2.5 was studied by measuring the turbidity (A(405 nm)) and viscosity (Ostwald capillary viscosimeter) of the samples. The structure of glucagon/gamma-CD complexes at pH 2.5 was studied with 2D-NMR. The presence of various CDs increased the chemical half-life of glucagon at pH 2.0 (37 degrees C, 0.01 M HCl, ionic strength 0.15) and prolonged the lag-time before aggregation at pH 2.5 (0.9% (w/v) NaCl in 3.2 mM HCl). The NMR studies showed that the side chains of all the aromatic amino acid residues (Phe6, Tyr10, Tyr13, Phe22, Trp25) and leucines (Leu14 and Leu26) of glucagon interacted with the cavities of the gamma-CD molecules. The present study shows that glucagon forms inclusion complexes with cyclodextrins in acidic solution, resulting in an improvement in its chemical and physical stability. |
| Databáze: | OpenAIRE |
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