Study of the solid state of carbamazepine after processing with gas anti-solvent technique

The purpose of this study was to investigate the influence of supercritical CO2 processing on the physico-chemical properties of carbamazepine, a poorly soluble drug. Using the gas anti-solvent (GAS) technique, this drug was precipitated from three different solvents (acetone, ethylacetate and dichloromethane) to study, in addition, the effect of these vehicles on the properties of the final product. The samples were analysed before and after treatment by scanning electron microscopy analysis (SEM) and laser granulometer for possible changes in the appearance of the crystals. Furthermore, the solid state of the samples was studied by means of X-Ray powder diffraction (XRD), differential scanning calorimetry (DSC), diffuse reflectance Fourier-transform infrared spectroscopy (DRIFT) and hot stage microscopy (HSM). Finally, the in vitro dissolution tests were carried out. The solid state analysis of treated and untreated with CO2 samples, illustrated that the applied methodology caused a transition from the starting form I to the form I as well as a dramatic change on crystal morphology, resulting in a final product mainly consisting of needle-shaped crystals, regardless of the chosen solvent. Furthermore, to investigate whether this phenomenon was due to the GAS process or the vehicles used, carbamazepine was precipitated from the same three solvents by traditional evaporation method (RV-samples). On the basis of this comparison, the solvents used were found to be responsible for the reorganisation into a different polymorphic form, whereas the potential of the GAS process to produce micronic needle shaped particles, having a enhanced dissolution rate compared to the RV-carbamazepine, was stated.