Lipid-based solubilization technology via hot melt extrusion: promises and challenges

Abstract

Introduction Self-emulsifying drug delivery systems (SEDDS) are a promising strategy to improve the oral bioavailability of poorly water-soluble drugs (PWSD). The excipients of SEDDS enable permeation through the mucus and gastro-intestinal barrier, inhibiting efflux transporters (e.g. P-glycoprotein) of drugs. Poor drug loading capacity and formulation instability are the main setbacks of traditional SEDDS. The use of polymeric precipitation inhibitors was shown to create supersaturable SEDDS with increased drug payload, and their solidification can help to overcome the instability challenge. As an alternative to several existing SEDDS solidification technologies, hot melt extrusion (HME) holds the potential for lean and continuous manufacturing of supersaturable solid-SEDDS. Despite being ubiquitously applied in solid lipid and polymeric processing, HME has not yet been widely considered for the preparation of SEDDS. Areas covered The review begins with the rationale why SEDDS as the preferred lipid-based delivery systems (LBDS) is suitable for the oral delivery of PWSD and discusses the common barriers to oral administration. The potential of LBDS to surmount them is discussed. SEDDS as the flagship of LBDS for PWSD is proposed with a special emphasis on solid-SEDDS. Finally, the opportunities and challenges of HME from the lipid-based excipient (LBE) processing and product performance standpoint are highlighted. Expert opinion HME can be a continuous, solvent-free, cost-effective, and scalable technology for manufacturing solid supersaturable SEDDS. Several critical formulations and process parameters in successfully preparing SEDDS via HME are identified.