Cyclodextrin solubilization of celecoxib: solid and solution state characterization
The low aqueous solubility of celecoxib (CCB) hampers its oral bioavailability and permeation from aqueous environment through biological membranes. The aim of this study was to enhance the aqueous solubility of CCB by complexation with cyclodextrin (CD) in the presence of water-soluble polymer. The effects of different CDs (αCD, βCD, γCD, 2-hydroxypropyl-β-cyclodextrin and randomly methylated β-cyclodextrin (RMβCD)) and mucoadhesive, water-soluble polymers (hydroxypropyl methylcellulose (HPMC), chitosan and hyaluronic acid) were investigated. The phase solubility profiles and CCB/CD complex characteristics were determined. RMβCD exhibited the greatest solubilizing effect of the two CDs tested. However, γCD was also selected for further investigations due to its safety profile. Addition of polymer to the aqueous CD solutions enhanced the CD solubilization. Formation of CCB/RMβCD/HPMC and CCB/γCD/HPMC ternary complexes resulted in 11 and 19-fold enhancement in the apparent complexation efficiency in comparison to their CCB/CD binary complex, respectively. The size of ternary complex aggregates in solution were determined to be from about 250 to about 350 nm. The data obtained from Fourier transform infrared, differential scanning calorimetry and powder X-ray diffraction indicated presence of CCB/CD inclusion complexes in the solid state. Proton nuclear magnetic resonance data demonstrated that CCB was partially and totally inserted into the hydrophobic central cavities of RMβCD and γCD.