Thermodynamically controlled crystallization of glucose pentaacetates from amorphous phase

Abstract

The α and β glucose pentaacetates are known sugar derivatives, which can be potentially used as stabilizers of amorphous phase of active ingredients of drugs (API). In the present work, crystallization behavior of equimolar mixture of α and β form in comparison to both pure anomers is revealed. It was shown that despite the same molecular interactions and similar molecular dynamics, crystallization from amorphous phase is significantly suppressed in equimolar mixture. Time dependent X-ray diffraction studies confirmed higher stability of the quenched amorphous equimolar mixture. Its tendency to crystallization is about 10 times lower than for pure anomers. Calorimetric studies revealed that the α and β anomers don’t form solid solutions and have eutectic point for xα = 0.625. Suppressed crystallization tendency in the mixture is probably caused by the altered thermodynamics of the system. The factors such as difference of free energy between crystalline and amorphous state or altered configurational entropy are probably responsible for the inhibitory effect.