Polymorphic Transitions of Carbamazepine During Grinding and Compression

Abstract
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 machine. The different parameters of compression, and hardness of resulting tablets were investigated. X Ray diffraction and Differential scanning calorimetry were carried out on the different samples of ground powders and on carefully crushed samples of each batch of tablets. The results point out at the best compressibility of dihydrate, and the most effective stability of the alpha form. However, the usual beta form remains stable in normal conditions of fabrication and storage.