Rational development of solid dispersions via hot-melt extrusion using screening, material characterization, and
Damir E Zecevic1, Karl G Wagner
1Boehringer-Ingelheim Pharma GmbH and Company KG, Biberach an der Riss, Germany.
Journal of Pharmaceutical Sciences
|May 11, 2013
Summary
This study introduces microscale tools for selecting drug formulations for hot-melt extrusion. These methods efficiently assess drug product attributes and process parameters, enabling successful scale-up and clinical trial supply manufacturing.
Area of Science:
- Pharmaceutical Sciences
- Chemical Engineering
- Materials Science
Background:
- Developing solubility-enhanced drug products requires efficient small-scale selection tools.
- Hot-melt extrusion (HME) is a key manufacturing process for such products.
Purpose of the Study:
- To establish and validate microscale and small-scale methods for predicting HME performance.
- To enable risk assessment for process scale-up.
Main Methods:
- Microscale evaluation using a hot-stage microscope (HSM) with 400 mg batches.
- Prototype formulation testing in a 5 mm twin-screw extruder (TSE).
- Process simulations using formulation properties and scale-up to larger TSEs (9-18 mm).
Main Results:
- HSM and small-scale TSE (5 mm) effectively predict drug product attributes and processing temperatures.
- Process simulations were refined through scale-up experiments.
- Successful manufacturing of clinical trial supply was achieved.
Conclusions:
- Microscale and small-scale HME assessments are predictive tools for drug product development.
- Integrated experimental and simulation approaches facilitate risk assessment and scale-up.
- This methodology supports efficient development even without extensive prior process experience.
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