Dissolution enhancement of active pharmaceutical ingredients in Eudragit E100 by melt extrusion coupled with supercritical carbon dioxide

Abstract : Melt extrusion is a well-known technique to disperse poorly water-soluble crystalline active pharmaceutical ingredients (APIs) in polymers for dissolution enhancement, which is achieved by destructing their crystal lattice. Its unquestionable advantages are that it is a solvent-free and high-throughput continuous manufacturing technology ensuring constant product quality, which is favoured by Process Analytical Technology guidelines, and the range of producible dosage forms is wide. At the same time, a clear disadvantage of conventional melt extrusion is that the heat sensitivity of some active compounds can be an obstacle to its application because most pharmaceutical-grade polymers can only be processed at a high temperature. The most promising way of providing milder processing conditions and hence reducing drug degradation is the utilization of supercritical carbon dioxide (scCO 2) as a reversible plasticizer [1]. In addition, it acts as a physical blowing agent and leaves behind a well-grindable, rigid product of high specific surface area, which can be extremely beneficial in the case of immediate release formulations owing to the great influence of this property on dissolution rate. In this study, BCS II classified thermally sensitive drugs, which need dissolution enhancement, were extruded with an acid-soluble, methacrylate-based polymer, Eudragit E100. We studied the influence of different operating parameters on the production of foamy extrudates: melt throughput, scCO 2 mass fraction, extrusion temperature and pressure. The samples were analysed for their physical properties: rigidity, porosity and characteristic pore size. API dispersion within the polymer matrix has also been characterized by X-ray diffraction, Raman mapping and dissolution tests.
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Martial Sauceau, Tamas Vigh, Élisabeth Rodier, Zsombor Kristof Nagy, György Marosi, et al.. Dissolution enhancement of active pharmaceutical ingredients in Eudragit E100 by melt extrusion coupled with supercritical carbon dioxide. 14th European meeting on supercritical fluids, ISASF, May 2014, Marseille, France. 6p. ⟨hal-01725186⟩

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