Interactions between carbamazepine and polyethylene glycol (PEG) 6000: characterisations of the physical, solid dispersed and eutectic mixtures

The influence of a hydrophilic carrier (PEG 6000) on the polymorphism of ca rbamazepine, an antiepileptic drug, was investigated in binary physical mix tures and solid dispersions by means of differential scanning calorimetry ( DSC), thermal gravimetry, hot-stage microscopy (HSM), and X-ray diffractome try, respectively. This study provides also an attempt to develop a method to calculate more precisely the eutectic composition. In rather ideal physi cal mixtures, carbamazepine was found as monoclinic Form III. In solid disp ersions, the drug was found to crystallize as trigonal Form II; a eutectic invariant in the PEG 6000-rich composition domain (6% of carbamazepine mass ) was evidenced by DSC experiments and confirmed by HSM observations. In th e binary phase diagram the ideal carbamazepine liquidus curve was located a t temperatures higher than the respective experimental ones. This suggests that drug can be maintained in the liquid state in the temperature-mass fra ction (T-x) region between the two carbamazepine liquidus curves. This indi cates in turn that attractive interactions occur between carbamazepine and PEG 6000-chains. These interactions have been also claimed to prevent carba mazepine from degradation into iminostilbene (a compound resulting from the chemical degradation of carbamazepine which is postulated to be responsibl e for the idiosyncratic toxicity of the drug) and thought to lead to the cr ystallization of metastable Carbamazepine II from melt. The negative excess entropy for eutectic mixtures indicated that the drug crystals are finely dispersed in the bulk of polymer chains. (C) 2001 Published by Elsevier Sci ence B.V.