Study of the Interaction of Dithranol with Heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin in Solution and in the Solid State

The interaction between dithranol and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMBCyD) has been investigated in aqueous solution containing isoascorbic acid (0·2% w/v) as antioxidant and in the solid state. The interaction in the solid state was studied by differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray powder diffractometry (XPD) and a dissolution-rate method. The extent of complexation between the two substances was poor, as indicated 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 various re-solidified physical mixtures of dithranol and of TMBCyD previously subjected to heating until melting of the TMBCyD. The loss of dithranol, owing to sublimation and degradation caused by the thermal treatment used, was less than 10%. In keeping with XPD and IR data, the phase diagram indicated that a complex was formed containing 13·7% dithranol (molar ratio 1:1) which had a congruent melting point at 164°C. The drug dissolution rate from the 1:1 complex was measurable, unlike that of the corresponding physical mixture, and was significantly increased when the complex was dispersed in the glassy matrix of TMBCyD, as it was in re-solidified mixtures containing 2–7% dithranol. The results show that the solubility of dithranol is increased significantly as a consequence of its interaction with TMBCyD, despite the low extent of complexation between the two substances.