Effects of Cyclodextrins and Phospholipids in Enhancing Dissolution of Indomethacin

Abstract

Inclusion complexes of indomethacin (IND) and β-cyclodextrins (β-CD) were prepared by the freeze drying methods. Solid dispersion of IND and Dimyristoylphosphatidylcholine (DMPC) was prepared as coprecipitate (CPPT) by the solvent method. These formulations were characterized by X-ray diffractometry and dissolution rate determinations. Dissolution of IND from β-CD inclusion complex was found to be 133 times faster than the corresponding pure IND, whereas it was about 4 times faster from a DMPC CPPT sample. Various derivatives of β-CDs showed variable rates of dissolution of IND. β-CD and most of the other derivatives showed almost instantaneous dissolution of IND at a molar ratio of 1:1 (IND:β-CD) except dimethyl-β-cyclodextrin (DMB) derivative, which showed a fairly constant release of IND over 90 minutes. DMB may, therefore, have the potential for use in the formulation of a constant-release preparation. X-ray diffraction spectra showed that indomethacin remained as amorphous state in CPPT or in inclusion complex. Thus, these formulations may have the potential to produce faster onset of action, reduced dosing and decreased GI irritation.