The use of rheology combined with differential scanning calorimetry to elucidate the granulation mechanism of an immiscible formulation system during continuous twin-screw melt granulation

T. Monteyne, L. Heeze, S.T.F.C. Mortier, K. Oldörp, R.M. Cardinaels, I. Nopens, Chr. Vervaet, J.-P. Remon, Th. De Beer

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)
1 Downloads (Pure)

Abstract

Purpose
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).

Methods
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).

Results
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.

Conclusion
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 WORDS
agglomeration mechanismcaffeine anhydrousglass transition temperaturegranule propertiessoluplus®tan(δ)
Original languageEnglish
Pages (from-to)2481-2494
Number of pages14
JournalPharmaceutical Research
Volume33
Issue number10
DOIs
Publication statusPublished - Oct 2016

Fingerprint

Dive into the research topics of 'The use of rheology combined with differential scanning calorimetry to elucidate the granulation mechanism of an immiscible formulation system during continuous twin-screw melt granulation'. Together they form a unique fingerprint.

Cite this