| Autor: |
R., Chabukswar Anuruddha, Jagdale S. C., M., Gandhi Preeti |
| Předmět: |
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| Zdroj: |
Journal of Drug Delivery & Therapeutics; May/Jun2019, Vol. 9 Issue 3, p252-256, 5p |
| Abstrakt: |
Objective: The objective of present work is to improve physicochemical and pharmacokinetic profile of poorly water soluble HIV protease inhibitor, ritonavir (RT) by preparing its amino acid conjugates. Methods: Ester conjugates of ritonavir with various amino acids were synthesized by a simple esterification process using dicyclohexyl carbodiimide (DCC) as a coupling agent. The synthesized compounds were characterized by thin layer chromatography (TLC), fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and mass spectroscopy. All conjugates were evaluated by saturation solubility and hydrolytic stability studies. Cytotoxicity and permeability studies were conducted using Caco-2 cell line. Results: All amino acid conjugates showed a significantly higher aqueous solubility compared to the pure RT. With respect to hydrolysis, alkaline hydrolysis of conjugates was rapid relative to acidic hydrolysis. No cytotoxicity was shown by conjugates for concentration as high as 100µg/ml, which indicates promising therapeutic potential. Permeability of RT across Caco-2 cell monolayers was improved by amino acid conjugation. Conclusion: In vitro studies demonstrated that amino acid conjugation of RT may be an effective strategy to improve its aqueous solubility as well as permeability and can be used to improve oral absorption and thereby oral bioavailability of protease inhibitors. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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