Dataset Information

Co-solvation effect on the binding mode of the ?-mangostin/?-cyclodextrin inclusion complex.

ABSTRACT: Cyclodextrins (CDs) have been extensively utilized as host molecules to enhance the solubility, stability and bioavailability of hydrophobic drug molecules through the formation of inclusion complexes. It was previously reported that the use of co-solvents in such studies may result in ternary (host:guest:co-solvent) complex formation. The objective of this work was to investigate the effect of ethanol as a co-solvent on the inclusion complex formation between ?-mangostin (?-MGS) and ?-CD, using both experimental and theoretical studies. Experimental phase-solubility studies were carried out in order to assess complex formation, with the mechanism of association being probed using a mathematical model. It was found that ?-MGS was poorly soluble at low ethanol concentrations (0-10% v/v), but higher concentrations (10-40% v/v) resulted in better ?-MGS solubility at all ?-CD concentrations studied (0-10 mM). From the equilibrium constant calculation, the inclusion complex is still a binary complex (1:1), even in the presence of ethanol. The results from our theoretical study confirm that the binding mode is binary complex and the presence of ethanol as co-solvent enhances the solubility of ?-MGS with some effects on the binding affinity with ?-CD, depending on the concentration employed.

SUBMITTER: Rungnim C

PROVIDER: S-EPMC4685766 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex.

Rungnim Chompoonut C Phunpee Sarunya S Kunaseth Manaschai M Namuangruk Supawadee S Rungsardthong Kanin K Rungrotmongkol Thanyada T Ruktanonchai Uracha U

Beilstein journal of organic chemistry 20151125

Cyclodextrins (CDs) have been extensively utilized as host molecules to enhance the solubility, stability and bioavailability of hydrophobic drug molecules through the formation of inclusion complexes. It was previously reported that the use of co-solvents in such studies may result in ternary (host:guest:co-solvent) complex formation. The objective of this work was to investigate the effect of ethanol as a co-solvent on the inclusion complex formation between α-mangostin (α-MGS) and β-CD, using ...[more]

PMID: 26734079

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Project description:Piroxicam (Px) is a nonsteroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis and rheumatoid arthritis. It is administered orally; however, its poor water solubility causes low loading to the nonconventional drug delivery systems (DDSs), such as electrospun fibers. Furthermore, the rapid dissolution of DDS and fast release of the embedded drugs are crucial for oral delivery of drugs to patients who are unconscious or suffering from dysphagia. In this regard, this study reports the development of rapidly dissolving cyclodextrin (CD)-based inclusion complex (IC) nanofibers by waterborne electrospinning for fast oral delivery of Px. Scanning electron microscopy analysis revealed the formation of bead-free fibers with a mean diameter range of 170-500 nm at various concentrations of Px; increasing the Px loading decreased the fiber diameter. The formation of IC was demonstrated by X-ray diffraction (XRD) analysis by the disappearance of crystalline peaks of Px. Likewise, differential scanning calorimetry (DSC) analysis showed the disappearance of the melting peak of the embedded Px due to IC formation. Both Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) confirmed the presence of Px within the fibers. 1H NMR experiments demonstrated Px preservation in the fibers after six months. Px-loaded nanofibers were employed for sublingual drug delivery. To mimic the environment of the mouth, the nanofibers were treated with artificial saliva, which revealed the instant dissolution of the nanofibers. Furthermore, dissolution experiments were performed on the tissues wetted with artificial saliva, where the dissolution of the fibers could be extended to a few seconds, demonstrating the suitability of the materials for sublingual oral drug delivery. Overall, this paper, for the first time, reports the rapid oral delivery of Px from polymer-free CD fibers produced by waterborne electrospinning without the requirement of any carrier polymer and toxic solvent.

Project description:BACKGROUND:Flunarizine dihydrochloride (FLN) is used in the prophylactic treatment of migraine, vertigo, occlusive peripheral vascular disease and epilepsy. Cyclodextrins (CDs) are chiral, truncated cone shaped macrocycles known for their inner hydrophobic and outer hydrophilic site. They form complexes with hydrophobic drug molecules and enhance the solubility and bioavailability of such compounds by enhancing drug permeability through mucosal tissues. NMR spectroscopy and computational docking have been recognized as an important tool for the interaction study of CDs-drug inclusion complexes in solution state. RESULTS:The structural assignments of FLN and ?-CD protons were determined by 1H NMR and 2D 1H-1H COSY NMR spectroscopy. 1H NMR spectroscopic studies of FLN, ?-CD and their mixtures confirmed the formation of ?-CD-FLN inclusion complex in solution. 1H NMR titration data for ?-CD-FLN inclusion complex showed 1:1 stoichiometry, an association constant of K a = 157 M-1 and change in Gibbs free energy of ?G?=?- 12.65 kJ mol-1. The binding constant of the ?-CD inclusion complex with two nearly similar structures, FLN and cetirizine dihydrochloride, were compared. Two-dimensional 1H-1H ROESY spectral data and molecular docking studies showed the modes of penetration of the aromatic rings from the wider rim side into the ?-CD cavity. The possible geometrical structures of the ?-CD-FLN inclusion complex have been proposed in which aromatic rings protrude close to the narrower rim of the ?-CD truncated cone. CONCLUSION:NMR spectroscopic studies of FLN, ?-CD and FLN:?-CD mixtures confirmed the formation of 1:1 inclusion complex in solution at room temperature. Two-dimensional 1H-1H ROESY together with molecular docking study confirmed that the F-substituted aromatic ring of FLN penetrates into ?-CD truncated cone and the tail of aromatic rings were proximal to narrower rim of ?-CD. The splitting of aromatic signals of FLN in the presence of ?-CD suggests chiral differentiation of the guest FLN by ?-CD.

Dataset Information

Co-solvation effect on the binding mode of the ?-mangostin/?-cyclodextrin inclusion complex.

Publications

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex.

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