M. Draguetbrughmans

Polymorphic Transitions of Carbamazepine During Grinding and Compression

Carbamazepine is a potent anticonvulsivant, but, irregular plasma levels are noticed. The variability of therapeutic efficiency can be attributed to interindividual sensibility, chronobiologic effect, but also to rates of dissolution which can differ when polymorphs are induced by technologic operations.Several crystalline forms of Carbamazepine have been characterized. As for us, we have studied three crystalline modifications which can be found in commercialized galenic forms: the most usual beta form, the alpha form and the dihydrate.The aim of this work was to investigate:- the behaviour of these three crystalline forms during compression- the possibility of crystalline structural changes under grinding and tabletting conditions. Indeed, polymorphous transformations may occur during technologic operations such as grinding or compression owing to the increase of internal energy.Grinding was performed in a ball mill for 15 and 60 minutes. Compression was carried out using an instrumented single punch ma...

The physicochemical properties of digoxin.

In a study of variations in the physicochemical properties of digoxin powder from several commercial sources, recrystallizations of digoxin were performed under several conditions. Polymorphs were not obtained whereas a pure amorphous form was formed under certain conditions. The amorphous form was more soluble and more stable under compression than was the crystalline form; nevertheless in contact with water it crystallized quickly. Traces of the crystalline form reduced the dissolution rate and stability of the amorphous form. Variations in the thermal behaviour of commercial samples can be explained by the presence of variable proportions of the amorphous form and also by thermal decomposition that varies from one sample to another and generally occurs at 160 degrees C and above.