Solubility and dissolution rate enhancement of ibuprofen by cyclodextrin based carbonate nanosponges

Abstract

In the present study nanotechnology approach, i.e., a cyclodextrin (CD) based carbonate nanosponge was used to improve the solubility and dissolution of ibuprofen. Solvent and ultrasound assisted methods were used to prepare nanosponges using two CDs (β-CD and 2-hydroxypropyl-β-CD (2HP-β-CD)) and a cross-linker (CL) diphenyl carbonate (DPC) in varying molar ratios. Nanosponges were investigated for their solubilizing efficiency and phase solubility studies. Structural analysis by Fourier transform infrared (FTIR) and powder X-ray diffraction (PXRD), thermo-analytical characterization by differential scanning calorimetry (DCS), morphology by scanning electron microscopy (SEM). In-vitro drug release followed by in-vivo analgesic and anti-inflammatory studies were performed. 2HP-β-CD based nanosponges (molar ratio 0.01:0.04) prepared by ultrasound assisted method showed the highest solubilizing efficiency (i.e., 4.28 folds). Stability constant values showed that all complexes were stable. Inclusion complexes of drug was confirmed by PXRD and DSC. SEM images showed porous structures confirming the formation of cross-linked network. Particle size was in the range of 296.8±64 to 611.7±32nm. In-vitro release studies showed enhanced dissolution profile from nanosponge formulation (~94% from I11) as compared to the pure drug (~45% Ibuprofen) in 120min. Significant (p<0.05) extent of pain inhibition and anti-inflammatory activity was observed for nanosponge formulation when compared with the pure drug. CD based carbonate nanosponges with better solubility, enhanced release profile, improved analgesic and anti-inflammatory activity were successfully formulated for ibuprofen.