THE EFFECT OF CYCLODEXTRINS ON THE SOLUBILITY AND STABILITY OF MEDROXYPROGESTERONE ACETATE AND MEGESTROL-ACETATE IN AQUEOUS-SOLUTION

The degradation of medroxyprogesterone acetate and megestrol acetate i n aqueous buffered solutions was investigated over the pH range 1-10. The degradation followed first-order kinetics. The pH-rate profiles we re of typical V-shape with a minimum at Ph between 4 and 5. In aqueous solutions the shelf-life of the drugs at physiological pH and 25-degr ees-C was estimated to be about 1 year. The effects of six cyclodextri n (CD) derivatives on the stability was investigated and 2-hydroxyprop yl-beta-cyclodextrin (HPbetaCD) of molar substitution (MS) 0.9 and met hyl-beta-cyclodextrin (MbetaCD) of degree of substitution (DS) 1.8 app eared to have the greatest stabilising effect. The drugs degraded 2.5- 4-times slower within the HPbetaCD and MbetaCD cavities than outside t he cavities. Of the two CD derivatives, MbetaCD DS 1.8 resulted in bet ter solubilisation of the drugs.