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). However, 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 loads, and their solidification can help to overcome the instability challenge. As an alternative to several existing SEDDS solidification technologies, hot melt extrusion (HME) has 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 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 is a continuous, solvent-free, cost-effective, and scalable technology for manufacturing solid supersaturable SEDDS. Several critical formulations and process parameters for successfully preparing SEDDS via HME are identified.

Graphical abstract

KEYWORDS:

• Poor water-soluble drugs (PWSD)
• lipid-based drug delivery systems (LBDS)
• oral administration barriers
• solid self-emulsifying drug delivery systems (S-SEDDS)
• hot melt extrusion (HME)

Article highlights

• The major barriers to the bioavailability of the orally administered PWSDs are the solubilization, mucus, permeation and pre-systemic metabolism barrier.

• Lipid-based delivery systems (LBDS), particularly self-emulsifying drug delivery systems (SEDDS) show high potential in improving oral bioavailability of poorly water-soluble drugs (PWSD) by mimicking the endogenous lipid metabolism pathway.

• The solid physical state of SEDDS is achieved via spray drying, freeze drying, adsorption on solid carriers, wet or melt granulation and hot melt extrusion (HME).

• HME is an unexploited way of preparing the new generation of solid SEDDS (S-SEDDS), which could be considered as “amorphous solid dispersions (ASD) with self-emulsification ability upon oral administration“.

• Formulation (material selection and compatibility, material and final product characterization, storage stability as well as process considerations (temperature, melt viscosity, HME setup)) of developing S-SEDDS via HME are presented in detail.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was funded through the Austria COMET Program by the Austrian Federal Ministry of Climate Action, Environment, Energy, Mobility, Innovation, and Technology; the Austrian Federal Ministry of Labour and Economy, the Federal State of Styria and SFG. The COMET Program is managed by the Austrian FFG.