Physicochemical characterization and in vitro dissolution behaviour of celecoxib-β-cyclodextrin inclusion complexes

Abstract

Cyclodextrins are chemically and physically stable molecules formed by the enzymatic modification of starch (1). They are cyclomalto oligosaccharides composed of six, seven or eight a-D-glucopyranose units (a-, b-, g-CD, respectively). Their hollow structure enables them to host a variety of molecules (guests) partially or entirely in their hydrophobic caving. These inclusion complexes exist both in aqueous solution and in solid state. As a result of complexation of compounds by cyclodextrins, the apparent solubility of the molecule can be altered (2), stability of the compound in the presence of light and oxidizing conditions is increased (3) and volatility of compounds is decreased (4). Many scientists have studied the cyclodextrin complexes of various NSAIDs such as valdecoxib, diclofenac, piroxicam, ketoprofen, etc. and have showed their superiority over physical mixtures (5-8).Celecoxib, 4-[(5-(4-methyl phenyl)-3-trifluoro methyl)-1H-pyrazol-1-yl] benzene sulfonamide is a non steroidal anti-inflammatory drug that is a specific inhibitor of COX-2 enzyme. Celecoxib is widely used in the treatment of rheumatoid and osteoarthritis. According to the biopharmaceutical classification system, celecoxib belongs to class II type In this study, attempts were made to investigate the effects of b-cyclodextrin (b-CD) on the aqueous solubility and dissolution rate of celecoxib. Inclusion complexes were prepared by the kneading method and characterized by SEM, NMR, IR, DSC, and X-ray powder diffraction. Dissolution rate of the complexes was significantly greater than that of the corresponding physical mixtures and pure drug, indicating that the formation of inclusion complex increased the solubility of the poorly soluble drug celecoxib.

An Investigation into the Dissolution Properties of Celecoxib Melt Extrudates: Understanding the Role of Polymer Type and Concentration in Stabilizing Supersaturated Drug Concentrations

“…It has been previously reported that hydrophilic carriers can interact with drug molecules in solution forming weakly soluble complexes mainly by electrostatic forces (ion–ion, ion–dipole, and dipole–dipole bonds) and occasionally by other types of forces like van der Waals forces and hydrogen bonding. , Carriers used to prepare solid dispersions may increase the solubility of drugs by forming weakly soluble complexes similar to those reported for cyclodextrins . Sinha et al , confirmed complex formation between CX and β-cyclodextrin using solution 1 H NMR based on downfield shifts (deshielding) for CX (H-1a and H-1b) protons resulting in significant enhancement in the solubility of CX. Additionally, complexation between β-cyclodextrin (β-CD) and fluconazole was confirmed by solution 1 H NMR which showed deshielding of the aromatic protons of fluconazole ( m -diflourophenyl ring).…”

Enhancement of dissolution rate and bioavailability of sulfamethoxazole by complexation with β-cyclodextrin

“…In aqueous solutions, CDs are able to form non-covalent inclusion complexes with various types of lipophilic drugs 5 . Encapsulation of a drug molecule is quite effective on many of its physicochemical properties and can result in increased aqueous solubility and stability 6,7 . Some additives such as water-soluble polymers or ion pairing agents also have a significant effect on the drug-cyclodextrin complex formation [8][9][10][11] .…”

Inclusion complexation of carbamazepine with different β-cyclodextrins buffer solutions

“…In the area of about 2930 cm -1 there is a band of asymmetric and symmetric valence C-H vibrations -CH2 group, but also valence C-H vibrations from -CHOH group. The bands at 1156.36 cm −1 correspond to -C-Cvibrations and at 1029.08 cm −1 (-OH bending vibration) [20] . Analysis of the complex FTIR spectra (figure 13.)…”