EFFECTS OF CYCLODEXTRINS AND PHOSPHOLIPIDS IN ENHANCING DISSOLUTION OF INDOMETHACIN

Inclusion complexes of indomethacin (IND) and beta-cyclodextrins (beta -CD) were prepared by the freeze drying methods. Solid dispersion of I ND and Dimyristoylphosphatidylcholine (DMPC) was prepared as coprecipi tate (CPPT) by the solvent method. These formulations were characteriz ed by X-ray diffractometry and dissolution rate determinations. Dissol ution of IND from beta-CD inclusion complex was found to be 133 times faster than the corresponding pure IND, whereas it was about 4 times f aster from a DMPC CPPT sample. Various derivatives of beta-CDs showed variable rates of dissolution of IND. beta-CD and most of the other de rivatives showed almost instantaneous dissolution of IND at a molar ra tio of 1:1 (IND:beta-CD) except dimethyl-beta-cyclodextrin (DMB) deriv ative, 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 i ndomethacin remained as amorphous state in CPPT or in inclusion comple x. Thus, these formulations may have the potential to produce faster o nset of action, reduced dosing and decreased GI irritation.