INTERACTION OF NAPROXEN WITH ALPHA-HYDROXYPROPYL, BETA-HYDROXYPROPYL,AND GAMMA-HYDROXYPROPYL CYCLODEXTRINS IN SOLUTION AND IN THE SOLID-STATE

Solid combinations of naproxen with amorphous hydroxypropyl derivative s of alpha-, beta-, and gamma-cyclodextrin with an average substitutio n degree per anhydroglucose unit of 0.6 were investigated for thermal behaviour (differential scanning calorimetry), drug crystallinity (X-r ay diffractometry), and dissolution rate (dispersed amount and rotatin g disc methods). Phase-solubility analysis and computer-aided molecula r modelling were carried out to study the inclusion complexation of na proxen with hydroxypropyl cyclodextrins. The cavity size of the host i s a selective factor for the solubilizing effect, complexing ability, and dissolution rate enhancement on naproxen, hydroxypropyl beta-cyclo dextrin being markedly the most effective derivative. No relationship was found between the decrease in crystallinity of the drug dispersed in the amorphous carrier matrix and the geometrical features of the cy clodextrin macrocycle.