Hot Melt Extrusion: A Process Overview and Use in Manufacturing Solid Dispersions of Poorly Water-Soluble Drugs

The high numbers of active pharmaceutical ingredients (APIs) within pharmaceutical pipelines that possess limited bioavailability is a major concern for the pharmaceutical industry. For APIs possessing high permeability but poor solubility, the formation of solid dispersions is an attractive approach to overcome such issues. Over the last decade, hot melt extrusion, a technology originating from the plastics industry, has become an interesting and versatile tool to manufacture solid dispersions. With an increasing number of publications and patents, hot-melt extrusion has been extensively demonstrated to provide efficient manufacture of solid dispersions with tailored drug release and bioavailability enhancement. In particular, hot-melt extrusion is considered economic and labour friendly over other processing techniques owing to its solventless and continuous fashion of operation. This chapter, introduces the basics of the HME technology including its equipment, operating principles, product characterization, and the selection of formulation materials. Different mechanisms of solubility enhancement and their evaluation post-manufacture are also featured. Moreover, selected pharmaceutical applications described in the scientific literature are reviewed with emphasis on improved API aqueous solubility. The high numbers of active pharmaceutical ingredients (APIs) within pharmaceutical pipelines that possess limited bioavailability are a major concern for the pharmaceutical industry. For APIs possessing high permeability but poor solubility, the formation of solid dispersions is an attractive approach to overcome such issues. Over the last decade, hot melt extrusion, a technology originating in the plastics industry, has become an interesting and versatile tool to manufacture solid dispersions. With an increasing number of publications and patents, hot melt extrusion has been extensively demonstrated to provide the efficient manufacture of solid dispersions with tailored drug release and bioavailability enhancement. In particular, hot melt extrusion is considered economic and labour-friendly over other processing techniques owing to its solventless and continuous fashion of operation. This chapter introduces the basics of the HME technology, including equipment, operating principles, product characterization, and the selection of formulation materials. Different mechanisms of solubility enhancement and their evaluation post-manufacture are also featured. Moreover, selected pharmaceutical applications described in the scientific literature are reviewed with an emphasis on improved API aqueous solubility. This edition first published 2013