Micronisation of carbamazepine through rapid expansion of supercritical solution (RESS)

A large number of pharmaceutical compounds are orally administered to the human body. If the drug shows a poor water-solubility and therewith low dissolution rate, a high dosage is needed which may cause undesired side effects to the human body. To improve the dissolution properties of these poorly water-soluble drugs, a large number of various strategies including micronisation, nano-emulsions and polymeric micelles are applied. In this paper we report on the formation of submicron carbamazepine particles by rapid expansion of supercritical solutions (RESS). The unprocessed and processed carbamazepine powder was characterized by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution rate measurements. Due to the existence of four different polymorphic forms of carbamazepine, one focus is on the modification or change of the crystal structure of carbamazepine caused by RESS. The experimental results show that the particle size can be reduced at least by a factor of 29 to median sizes between 0.43 and 0.9 mu m and that pure C-monoclinic carbamazepine particles can be produced for pre-expansion temperatures >= 363 K. The dissolution rate of the product at pH 2 and 310 K could be enhanced in comparison to the unprocessed material. (C) 2011 Elsevier B.V. All rights reserved.