EFFECTS OF SOME HYDROTROPIC AGENTS ON THE FORMATION OF INDOMETHACIN BETA-CYCLODEXTRIN INCLUSION-COMPOUNDS/

The influence of the water structure promoters, mannitol and sucrose, on the indomethacin/beta-cyclodextrin inclusion process at different p H values was evaluated using the phase solubility method and circular dichroism spectroscopy. The effect of mannitol and sucrose on the tota l solubilizing activity of beta-cyclodextrin as well as on the stabili zation of the complex was moderate, and depended strongly on the pH va lue of the medium. The most pronounced effect on the association const ant of the indomethacin inclusion compound was observed in KCl/HCl buf fer of pH 1.6, because mannitol and sucrose, in the absence of beta-cy clodextrin, approximately double the indomethacin solubility so that t he constant value decreases. On the other hand, a very strong complex formation between indomethacin and beta-cyclodextrin was observed in a cid medium (KCl/HCl buffer, pH = 1.6), a fact not much discussed in th e literature. The apparent association constant of the inclusion compo und formed in the absence of mannitol or sucrose was found to be of th e same order of magnitude as for the complex formed at pH 6.8. Changes in the optical activity of the indomethacin/beta-cyclodextrin inclusi on complex were registered in the presence of sucrose, which interacts more strongly than mannitol with water molecules, and could probably adhere to the surface of the inclusion complex, thus changing its conf iguration and environment.