Control Strategy Considerations for Continuous Manufacturing Using Hot Melt Extrusion *
Hot melt extrusion (HME) achieves the molecular mixing of active pharmaceutical ingredients (API) and excipients at temperatures above their glass transition temperatures and/or melting temperature. This chapter focuses on the scientific considerations when developing and defining the control strategy for continuous manufacture of pharmaceuticals using hot melt extrusion. Downstream continuous processing for HME usually includes a sizing step, which can include cutting, multistage milling, and/or particle size selection. One of the aspects of process development specific to continuous manufacturing is the understanding of residence time distribution through the processing steps and the understanding of the degree of intermixing between processing steps. The ability of the HME process to divert or reject material that is nonconforming based on prespecified quality criteria is a key element of the continuous manufacturing control strategy. HME, being a continuous process, is much easier to scale up compared to a batch process. The technology transfer for scale-up requires a thorough characterization of the HME process.