S. Cafaggi et al., Study of the interaction of dithranol with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin in solution and in the solid state, J PHARM PHA, 50(3), 1998, pp. 257-264
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.