Study of the interaction of dithranol with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin in solution and in the solid state

The interaction between dithranol and heptakis(2,3,6-tri-O-methyl)-beta-cyc lodextrin (TMBCyD) has been investigated in aqueous solution containing iso ascorbic acid (0.2% w/v) as antioxidant and in the solid state. The interac tion in the solid state was studied by differential scanning calorimetry (D SC), infrared spectroscopy (IR), X-ray powder diffractometry (XPD) and a di ssolution-rate method. The extent of complexation between the two substances was poor, as indicate d by the low value of the slope of the linear part of the solubility curve. A phase diagram was constructed by measuring the thermal behaviour of vari ous re-solidified physical mixtures of dithranol and of TMBCyD previously s ubjected to heating until melting of the TMBCyD. The loss of dithranol, owi ng to sublimation and degradation caused by the thermal treatment used, was less than 10%. In keeping with XPD and IR data, the phase diagram indicate d that a complex was formed containing 13.7% dithranol (molar ratio 1:1) wh ich had a congruent melting point at 164 degrees C. The drug dissolution ra te from the 1:1 complex was measurable, unlike that of the corresponding ph ysical mixture, and was significantly increased when the complex was disper sed in the glassy matrix of TMBCyD, as it was in re-solidified mixtures con taining 2-7% dithranol. The results show that the solubility of dithranol is increased significantl y as a consequence of its interaction with TMBCyD, despite the low extent o f complexation between the two substances.