Hot-Melt Extrusion

For drugs with low solubility or bioavailability, Capsugel offers a wide range of formulation options and technologies that maximize the opportunity for development and commercial success of drug candidates.

Effective delivery of many of BCS class II compounds with low solubility can be enabled with amorphous dispersions made by hot-melt extrusion (HME). HME manufacture of amorphous dispersion involves the melting of a drug substance with an appropriate polymeric excipient in a co-rotating twin-screw extruder. Functional excipients, such as surfactants, may be added to aid in the extrusion process or to improve dissolution performance upon administration. When cooled, the extrudate generally consists of a single-phase amorphous glassy matrix that can be milled to the desired particle size and incorporated into traditional tablet or capsule dosage forms.

Our breadth of solubilization technologies and depth of fundamental understanding allows the use of a creative, fit-for-purpose, drug-development approach. This means we may focus on low-risk, drug-sparing spray-dried dispersions (SDDs) in early development and transition to HME formulations when and where appropriate based on considerations such as drug properties, dose and cost of goods. The use of extruders at a wide range of scales enables production of extrudates using current Good Manufacturing Practice (cGMP) and development (non-cGMP) processes for use in clinical studies and at small commercial levels.

HME Formulation Selection & Process Development

Formulation & Process Development flow chart

Capability Highlights

  • Over a decade of experience in amorphous dispersion and HME formulation development
  • Extensive experience formulating solid dosage forms incorporating HME intermediates
  • Development and cGMP extrusion manufacturing capabilities (18-, 19- and 27mm twin-screw extruders) with a large selection of prefabricated dies
  • Full selection of ancillary feeding, cooling, pelletizing and milling equipment
  • Rational selection of technology based on physicochemical properties of drug, development stage, and cost of goods implications
  • Predictive model-based approach to performance evaluation, stability assessment and process definition to minimize development time and risk to clients' programs.

Available Equipment

Twin Screw Mixers / Hot-Melt Extruders

TYPE & MODEL MANUFACTURER SCALE CGMP NON CGMP
ZSE-18, 18 mm Leistritz 0.1 - 10 kg/hr X X
MP-PH, 19 mm Baker Perkins 0.1 - 10 kg/hr   X
ZSE-27, 27 mm Leistritz 1 - 25 kg/hr X X

Additional accessories for all extruders:

K-Tron loss-in-weight powder feeders, liquid feeders and pelletizer, Sandvik chill roll, Leistritz side stuffer