Preparation and in-vitro release rate of fentanyl–cyclodextrin complexes for prolonged action in epidural analgesia
| Autor: | Margriet Gabriels, Frederic Camu, Chantal Holvoet, Jacqueline Plaizier-Vercammen, Y. Vander Heyden |
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| Přispěvatelé: | Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel, Critical Care |
| Rok vydání: | 2003 |
| Předmět: |
Pharmaceutical Science
Pharmacology Dosage form Inclusion compound Fentanyl chemistry.chemical_compound Drug Stability In vivo medicine Solubility Epidural administration Maltose Chromatography High Pressure Liquid chemistry.chemical_classification Cyclodextrins Chromatography Cyclodextrin beta-Cyclodextrins Membranes Artificial Hydrogen-Ion Concentration 2-Hydroxypropyl-beta-cyclodextrin Analgesia Epidural Analgesics Opioid chemistry Delayed-Action Preparations Liberation Ethers medicine.drug |
| Zdroj: | Vrije Universiteit Brussel |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/s0378-5173(03)00368-5 |
| Popis: | Fentanyl was complexed with cyclodextrin derivatives with the intention to obtain parenteral solutions able to provide prolonged analgesia following epidural administration. Three cylodextrins (CDs) suitable for parenteral use were used: hydroxypropyl-beta-cyclodextrin (HP-beta-CD), sulfobutylether-beta-cyclodextrin (SBE-7-beta-CD), and maltosyl-beta-cyclodextrin (malt-beta-CD). Analysis of fentanyl was done with HPLC-UV. The inclusion capacity of HP-beta-CD was determined from phase-solubility diagrams at pH 6.5, 7.2 and 8.0, and those of SBE-7-beta-CD and of malt-beta-CD at pH 8.0. Solubility of fentanyl increased linearly (i) as a function of the CD concentration, and (ii) with decreasing pH. Complexation was highest with HP-beta-CD and malt-beta-CD, much higher than with SBE-7-beta-CD, with stability constants at pH 8.0 of 801, 729 and 1309 M(-1), respectively. The CD concentration was calculated to obtain a fentanyl-CD formulation, with the desired amount free fentanyl as loading dose in solution and the rest complexed with CD, as reservoir for prolonged action. A suitable membrane and a release-rate apparatus were selected for in-vitro release-rate studies. Best results were obtained with Spectrapor membranes and a home-made release-rate apparatus. Release rate was evaluated in static and dynamic conditions. For both modes, the release rate of fentanyl decreased as a function of CD concentration, due to complex formation of fentanyl, which suggests the possibility to provide prolonged pharmacodynamic effects in vivo. |
| Databáze: | OpenAIRE |
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