Study of the inclusion of diflunisal within 2-hydroxipropyl-β-ciclodextrin
Abstract
Diflunisal (HDif) is a non-steroidal analgesic and anti-inflammatory drug, whose therapeutic effects result from the inhibition of prostaglandin production. Anti-inflammatory drugs inclusion complexes within 2-hydroxypropyl-β-cyclodextrin (2HP−βCD), increase drug solubility in water and reduce drug side effects; for example, in cyclodexÒ (piroxicam-βCD). In this work, the formation of the complex of anionic diflunisal (Dif) with 2HP−βCD was studied by isothermal calorimetric titration, in water at 30 ºC and neutral pH. The inclusion is exothermic (ΔHº = −3.13 kcal/mol), generates entropy (TΔSº = 2.20 kcal/mol) and is spontaneous (ΔGº = −5.24 kcal/mol). In addition, the molecular modeling of the inclusion complex was carried out, finding that van der Waals-type interactions and hydrogen bonds are responsible for the stability of the complex.
Downloads
References
Crini, G. (2014). Review: A History of Cyclodextrins. Chem Rev, 114(21), 10940-10975. DOI: 10.1021/cr500081p
Chatziathanasiadou, M. V., Mavromoustakos, T., Tzakos, A. G. (2021). Unveiling the thermodynamic aspects of drug-cyclodextrin interactions through isothermal titration calorimetry. Methods Mol Biol 2207, 187–98. DOI: 10.1007/978-1-0716-0920-0_15
Hipólito-Nájera, A.R., del Rosario Moya-Hernández, M., Rojas-Hernández, A. Gómez-Balderas, R. Interaction of indomethacin–cyclodextrins in water by UV–Vis and ITC. J Incl Phenom Macrocycl Chem 95, 55–62 (2019). DOI: 10.1007/s10847-019-00915-9
Hohenstein, E. G., Chill, S. T., & Sherrill, C. D. (2008). Assessment of the Performance of the M05−2X and M06−2X Exchange-Correlation Functionals for Noncovalent Interactions in Biomolecules. J Chem Theory Comp, 4(12), 1996-2000. DOI: 10.1021/ct800308k
Kumar, P. S. V., Raghavendra, V., Subramanian, V. (2016). Bader’s Theory of Atoms in Molecules (AIM) and its Applications to Chemical Bonding. J Chem Sci, 128(10), 1527-1536. DOI: 10.1007/s12039-016-1172-3
Lu, T., & Chen, Q. (2022). Independent gradient model based on Hirshfeld partition: A new method for visual study of interactions in chemical systems. J Comp Chem, 43(8), 539-555. DOI: 10.1002/jcc.26812
Mardirossian, N., Head-Gordon, M. (2017). Thirty years of density functional theory in computational chemistry: An overview and extensive assessment of 200 density functionals. Mol Phys, 115(19), 2315-2372. DOI: 10.1080/00268976.2017.1333644
Marenich, A.V., Cramer, C.J., Truhlar, D.G. (2009) Universal solvation model based on solute electron density and a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113, 6378–6396. DOI: 10.1021/jp810292n
Rekharsky, M. V., Inoue, Y. (1998). Complexation Thermodynamics of Cyclodextrins. Chem Rev, 98(5), 1875-1918. DOI: 10.1021/cr970015o
Roselet, L. S., Kumari, P. J. (2020). An investigation on host-guest complexation of Metformin hydrochloride with hydroxypropyl-α-cyclodextrin for enhanced oral bioavailability. Mater Today, 21:514–518. DOI: 10.1016/j.matpr.2019.06.650
Shimpi, S., Chauhan, B., Shimpi, P. (2005). Cyclodextrins: application in different routes of drug administration. Acta Pharm, 55(2):139-56. PMID: 16179128.
Vardanyan, R. S., Hruby, V. J. (2006). Analgesics. En Synthesis of Essential Drugs (pp. 19-55). Elsevier. DOI: 10.1016/B978-044452166-8/50003-0
Copyright (c) 2023 Rodolfo Gómez-Balderas, León Daniel Ponce-Pérez, Jeovani González-Barbosa, Norma Rodríguez-Laguna
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
