Solubility and partitioning of carbamazepine in a two-phase supercritical carbon dioxide/polyvinylpyrrolidone system

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Supercritical carbon dioxide (scCO2) processing of drug/polymer mixtures is an environmentally friendly means of creating an impregnated polymeric carrier to enhance the aqueous dissolution rate of drugs that exhibit poor water solubility or are thermally labile. However, the role of drug solubilization and its interaction with the polymer during scCO2 processing on the extent and rate of dissolution has been ambiguous. In this study, we examine the rate of dissolution of carbamazepine (CBZ), a hydrophobic drug for treating epilepsy, in scCO2 (90-200 bar, 35 °C and 45 °C) and its partitioning into polyvinylpyrrolidone (PVP, 10 and 29 K MW) using in situ UV-vis spectroscopy. Our results show that partitioning occurs by surface adsorption and impregnation within the polymer matrix. These processes are linked to plasticization, which is dependent on PVP molecular weight, and temperature and pressure during treatment. The rate and extent of CBZ solubility is also controlled by treatment condition. The ability to tune polymer and drug simultaneously can be used to control the nature and extent of drug loading. © 2010 Elsevier B.V. All rights reserved.

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International Journal of Pharmaceutics