(233s) Process Development for Continuous Extrusion and Pelletization of a Heat and Shear-Sensitive Formulation
- Conference: AIChE Annual Meeting
- Year: 2016
- Proceeding: 2016 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
Monday, November 14, 2016 - 3:15pm-5:45pm
In this case an immediate release formulation was developed containing a BCS class II with poor solubility. The formulation consists of the API, Eudragit E and Methocel E5. Methocel E5 was added in order to achieve immediate release from the very dense pellet. Besides the shear and heat sensitivity of Methocel E5, a high pressure drop across the extrusion die is obtained due to the high viscosity and the yield point. Therefore, the extrusion process line consists of (1) a hot-melt extruder with a melt pump, (2) and a strand pelletizer. The strand pelletizer is used to directly produce pellets of small size (x50 = 1000 Âµm) for subsequent continuous tableting.
The process development focused on the split-feeding unit, the intake zone, the temperature profile, the die plate temperature and the die plate design. After developing a stable process, a screening DoE was performed to investigate content uniformity, dissolution behavior, pellet size and material degradation. Moreover, the residence time distribution was determined.
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