CONSTRUCTION OF A PHASE DIAGRAM FOR ITRACONAZOLE/EC 20 CPS SOLID DISPERSIONS PREPARED BY HOT STAGE EXTRUSION WITH AND WITHOUT INJECTION OF PRESSURIZED CO_2

摘要

Although a significant number of pharmaceutical examples of hot stage extrusion have been described in literature [1, 2], one of the major drawbacks of hot stage extrusion is its limited applicability to thermally stable products. For a number of active substances (and excipients), hot stage extrusion cannot be used due to thermal degradation and subsequent loss of its activity [3]. In these cases, a plasticizer can be added in order to reduce the viscosity of the mixture in the extruder and therefore to lower the process temperature settings. However, added plasticizers usually remain in the product, thus affecting its properties and performance. Typically, conventional plasticizers such as triacetin or polyethylene glycol are used in a concentration range of 5 up to 30 wt% of the extrudable mass [4-6]. Therefore, it is beneficial to have a temporary plasticizer that lowers the processing temperature during hot stage extrusion without being present in the final formulation. Previous work has shown that pressurized carbon dioxide, when injected during hot stage extrusion, worked as a temporary plasticizer for a number of pharmaceutically acceptable polymers, including PVP-VA 64, eudragit E100 and EC 20 cps [7]. Verreck et al. also describe the injection of carbon dioxide during hot stage extrusion of itraconazole with PVPVA 64 and itraconazole with EC 20 cps and confirm the plasticization of the product by pressurized carbon dioxide [8,9]. To better understand the solid dispersion, a phase diagram of itraconazole and EC 20 cps was constructed using hot stage extrusion with and without CO_2 injection.