The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation
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Twin screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to continuous granulation of moisture sensitive drugs. However, knowledge of the material behavior during TS HMG is crucial to optimize the formulation, process and resulting granule properties. The aim of this study was to evaluate the agglomeration mechanism during TS HMG using a rheometer in combination with differential scanning calorimetry (DSC).
An immiscible drug-binder formulation (caffeine-Soluplus®) was granulated via TS HMG in combination with thermal and rheological analysis (conventional and Rheoscope), granule characterization and Near Infrared chemical imaging (NIR-CI).
A thin binder layer with restricted mobility was formed on the surface of the drug particles during granulation and is covered by a second layer with improved mobility when the Soluplus® concentration exceeded 15% (w/w). The formation of this second layer was facilitated at elevated granulation temperatures and resulted in smaller and more spherical granules.
The combination of thermal and rheological analysis and NIR-CI images was advantageous to develop in-depth understanding of the agglomeration mechanism during continuous TS HMG and provided insight in the granule properties as function of process temperature and binder concentration.
KEY WORDSagglomeration mechanism caffeine anhydrous glass transition temperature granule properties soluplus® tan(δ)
Active pharmaceutical ingredient
Attenuated Total Reflection
Differential scanning calorimetry
Fourier Transform Infrared
Complex shear modulus
Granule size distribution
Hot melt granulation
Near Infrared chemical imaging
Standard Normal Variate
Glass transition temperature
- TS HMG
Twin screw hot melt granulation
ACKNOWLEDGMENTS AND DISCLOSURES
Financial support for this research from the Agency for Innovation by Science and Technology (IWT - Ph.D. fellowship Tinne Monteyne) and Fund for Scientific Research Flanders (FWO Flanders - Postdoc fellowship Severine Therese F.C. Mortier) are gratefully acknowledged. BASF is acknowledged for sending large amounts of caffeine and Soluplus®. Thermo Fisher Scientific (Karlsruhe) is appreciatively acknowledged for giving me the opportunity to use their rheometers in parallel for a long period of time.
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