Complexes of Ibuprofen Thiazolidin-4-One Derivatives with β-Cyclodextrin: Characterization and In Vivo Release Profile and Biological Evaluation.
Ioana Mirela VasincuMaria ApotrosoaeiFlorentina LupascuAndreea Teodora IacobSimona-Eliza GiuscaIrina-Draga CaruntuNarcisa-Laura MarangociAnca Roxana PetroviciGabriela-Dumitrita StanciuBogdan Ionel TambaBianca-Stefania ProfireAlin-Viorel FocsaMariana PintealaLenuța ProfirePublished in: Pharmaceutics (2023)
Generally, NSAIDs are weakly soluble in water and contain both hydrophilic and hydrophobic groups. One of the most widely used NSAIDs is ibuprofen, which has a poor solubility and high permeability profile. By creating dynamic, non-covalent, water-soluble inclusion complexes, cyclodextrins (CDs) can increase the dissolution rate of low aqueous solubility drugs, operating as a drug delivery vehicle, additionally contributing significantly to the chemical stability of pharmaceuticals and to reducing drug-related irritability. In order to improve the pharmacological and pharmacokinetics profile of ibuprofen, new thiazolidin-4-one derivatives of ibuprofen ( 4b , 4g , 4k , 4m ) were complexed with β-CD , using co-precipitation and freeze-drying. The new β-CD complexes ( β-CD-4b , β-CD-4g , β-CD-4k , β-CD-4m ) were characterized using scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and a phase solubility test. Using the AutoDock-VINA algorithm included in YASARA-structure software, we investigated the binding conformation of ibuprofen derivatives to β-CD and measured the binding energies. We also performed an in vivo biological evaluation of the ibuprofen derivatives and corresponding β-CD complexes, using analgesic/anti-inflammatory assays, as well as a release profile. The results support the theory that β-CD complexes ( β-CD-4b , β-CD-4g , β-CD-4k , β-CD-4m ) have a similar effect to ibuprofen derivatives ( 4b , 4g , 4k , 4m ). Moreover, the β-CD complexes demonstrated a delayed release profile, which provides valuable insights into the drug-delivery area, focused on ibuprofen derivatives.