Melt Extrusion

Abstract

Techniques to overcome poor aqueous solubility of active pharmaceutical ingredients (APIs) continue to gain interest with a reported 30 % of marketed compounds classified as BCS II and 10 % classified as BCS IV. Approximately 70 % of new chemical entities under development may be classified as BCS II and another 20 % as BCS IV (Siew 2015). Driven by this need to enable therapies of poorly soluble compounds through the generation of amorphous solid dispersions, pharmaceutical scientists have adapted a number of technologies from other industries to provide reliable and robust drug product manufacturing. Melt extrusion is an example of such a technology. Originally developed in the plastics industry over a century ago, it has been applied to pharmaceutical systems over the last three decades to generate some of the most cutting-edge delivery systems seen in the industry to date. The well-characterized nature of the process provides for ease of scale-up and process optimization, while also affording benefits of continuous manufacturing and adaptability to process analytical technology in an ever-changing regulatory and fiscal environment where manufacturing efficiencies must be maximized to reduce cost and improve product quality. This chapter details the basic engineering principles of the melt extrusion process and provides a fundamental understanding of formulation development of melt-extruded solid dispersions for bioavailability enhancement. Several recent case studies are also described to highlight the applicability of the technology to developmental and marketed products within the industry.