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The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation.
Pharm Res. 2016 10; 33(10):2481-94.PR

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.

Authors+Show Affiliations

Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. Tinne.Monteyne@Ugent.be.Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653,, 9000, Ghent, Belgium.Center for Material Characterization of Products, Thermo sher Dieselstrasse 4,, 76227, Karlsruhe, Germany.Polymer Technology, Department of Mechanical Engineering, Eindhoven University of Technology, Gemini-Zuid 4.142, 5600, Eindhoven, The Netherlands.BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653,, 9000, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460,, 9000, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460,, 9000, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27335024

Citation

Monteyne, Tinne, et al. "The Use of Rheology Combined With Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation." Pharmaceutical Research, vol. 33, no. 10, 2016, pp. 2481-94.
Monteyne T, Heeze L, Mortier ST, et al. The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation. Pharm Res. 2016;33(10):2481-94.
Monteyne, T., Heeze, L., Mortier, S. T., Oldörp, K., Cardinaels, R., Nopens, I., Vervaet, C., Remon, J. P., & De Beer, T. (2016). The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation. Pharmaceutical Research, 33(10), 2481-94. https://doi.org/10.1007/s11095-016-1973-6
Monteyne T, et al. The Use of Rheology Combined With Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation. Pharm Res. 2016;33(10):2481-94. PubMed PMID: 27335024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation. AU - Monteyne,Tinne, AU - Heeze,Liza, AU - Mortier,Severine Therese F C, AU - Oldörp,Klaus, AU - Cardinaels,Ruth, AU - Nopens,Ingmar, AU - Vervaet,Chris, AU - Remon,Jean-Paul, AU - De Beer,Thomas, Y1 - 2016/06/22/ PY - 2016/03/11/received PY - 2016/06/14/accepted PY - 2016/6/24/entrez PY - 2016/6/24/pubmed PY - 2017/12/6/medline KW - agglomeration mechanism KW - caffeine anhydrous KW - glass transition temperature KW - granule properties KW - soluplus® KW - tan(δ) SP - 2481 EP - 94 JF - Pharmaceutical research JO - Pharm Res VL - 33 IS - 10 N2 - 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. SN - 1573-904X UR - https://www.unboundmedicine.com/medline/citation/27335024/The_use_of_Rheology_Combined_with_Differential_Scanning_Calorimetry_to_Elucidate_the_Granulation_Mechanism_of_an_Immiscible_Formulation_During_Continuous_Twin_Screw_Melt_Granulation_ L2 - https://doi.org/10.1007/s11095-016-1973-6 DB - PRIME DP - Unbound Medicine ER -