Physicochemical characterization and in vitro dissolution performance of ibuprofen-Captisol® (sulfobutylether sodium salt of β-CD) inclusion complexes

The aim of the present research work was to explore the impact of ibuprofen-captisol (R) (sulfobutylether sodium salt of beta-CD) inclusion complexes on in vitro dissolution performance. Phase solubility studies of ibuprofen using the carrier captisol (R) had generated A(L)-type profiles which indicated the formation of 1:1 stoichiometric inclusion complexes. The study revealed that more stable complexes of ibuprofen-captisol (R) were formed in double distilled water compared to phosphate buffer (pH 7.2) as more fraction of the drug is in un-ionized form. Ibuprofen-captisol (R) complexes were prepared by (i) kneading and (ii) freeze-drying technique with the various drug-carrier ratio (1:1, 1:3 and 1:5 w/w). Complex formation was explained on the basis of physical mixtures (PMs) of identical compositions. Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Scanning electron microscope (SEM) and Molecular docking studies were carried out to establish the inclusion complexation. Molecular docking confirmed the possibility of forming a complex between drug and polymer, and it was evident from the energy-minimized structure of the drug-polymer complex. Minimization of energy suggested the formation of a stable drug-polymer complex with binding energy of (-) 3.6 kcal mol(-1). The negative docking energy of the complex formation justifies the reason of its solubility enhancement. The complexes prepared by freeze-drying technique were found to be superior in the enhancement of in vitro dissolution rate of ibuprofen when compared to that of complexes prepared by kneading technique. (C) 2018 Elsevier B.V. All rights reserved.