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Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties.
Eur J Pharm Biopharm. 2016 Oct; 107:249-62.EJ

Abstract

The pharmaceutical industry has a growing interest in alternative manufacturing models allowing automation and continuous production in order to improve process efficiency and reduce costs. Implementing a switch from batch to continuous processing requires fundamental process understanding and the implementation of quality-by-design (QbD) principles. The aim of this study was to examine the relationship between formulation-parameters (type binder, binder concentration, drug-binder miscibility), process-parameters (screw speed, powder feed rate and granulation temperature), granule properties (size, size distribution, shape, friability, true density, flowability) and tablet properties (tensile strength, friability, dissolution rate) of four different drug-binder formulations using Design of experiments (DOE). Two binders (polyethylene glycol (PEG) and Soluplus®) with a different solid state, semi-crystalline vs amorphous respectively, were combined with two model-drugs, metoprolol tartrate (MPT) and caffeine anhydrous (CAF), both having a contrasting miscibility with the binders. This research revealed that the granule properties of miscible drug-binder systems depended on the powder feed rate and barrel filling degree of the granulator whereas the granule properties of immiscible systems were mainly influenced by binder concentration. Using an amorphous binder, the tablet tensile strength depended on the granule size. In contrast, granule friability was more important for tablet quality using a brittle binder. However, this was not the case for caffeine-containing blends, since these phenomena were dominated by the enhanced compression properties of caffeine Form I, which was formed during granulation. Hence, it is important to gain knowledge about formulation behavior during processing since this influences the effect of process parameters onto the granule and tablet properties.

Authors+Show Affiliations

Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: 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. Electronic address: Jochem.Vancoillie@UGent.be.Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: JeanPaul.Remon@UGent.be.Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: thomas.debeer@ugent.be.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27449628

Citation

Monteyne, Tinne, et al. "Continuous Melt Granulation: Influence of Process and Formulation Parameters Upon Granule and Tablet Properties." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 107, 2016, pp. 249-62.
Monteyne T, Vancoillie J, Remon JP, et al. Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties. Eur J Pharm Biopharm. 2016;107:249-62.
Monteyne, T., Vancoillie, J., Remon, J. P., Vervaet, C., & De Beer, T. (2016). Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 107, 249-62. https://doi.org/10.1016/j.ejpb.2016.07.021
Monteyne T, et al. Continuous Melt Granulation: Influence of Process and Formulation Parameters Upon Granule and Tablet Properties. Eur J Pharm Biopharm. 2016;107:249-62. PubMed PMID: 27449628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties. AU - Monteyne,Tinne, AU - Vancoillie,Jochem, AU - Remon,Jean-Paul, AU - Vervaet,Chris, AU - De Beer,Thomas, Y1 - 2016/07/20/ PY - 2016/05/28/received PY - 2016/07/14/revised PY - 2016/07/18/accepted PY - 2016/7/25/entrez PY - 2016/7/28/pubmed PY - 2017/3/11/medline KW - Continuous hot melt granulation (HMG) KW - DOE KW - Drug binder interaction KW - Granule and tablet properties KW - Solid state binder SP - 249 EP - 62 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 107 N2 - The pharmaceutical industry has a growing interest in alternative manufacturing models allowing automation and continuous production in order to improve process efficiency and reduce costs. Implementing a switch from batch to continuous processing requires fundamental process understanding and the implementation of quality-by-design (QbD) principles. The aim of this study was to examine the relationship between formulation-parameters (type binder, binder concentration, drug-binder miscibility), process-parameters (screw speed, powder feed rate and granulation temperature), granule properties (size, size distribution, shape, friability, true density, flowability) and tablet properties (tensile strength, friability, dissolution rate) of four different drug-binder formulations using Design of experiments (DOE). Two binders (polyethylene glycol (PEG) and Soluplus®) with a different solid state, semi-crystalline vs amorphous respectively, were combined with two model-drugs, metoprolol tartrate (MPT) and caffeine anhydrous (CAF), both having a contrasting miscibility with the binders. This research revealed that the granule properties of miscible drug-binder systems depended on the powder feed rate and barrel filling degree of the granulator whereas the granule properties of immiscible systems were mainly influenced by binder concentration. Using an amorphous binder, the tablet tensile strength depended on the granule size. In contrast, granule friability was more important for tablet quality using a brittle binder. However, this was not the case for caffeine-containing blends, since these phenomena were dominated by the enhanced compression properties of caffeine Form I, which was formed during granulation. Hence, it is important to gain knowledge about formulation behavior during processing since this influences the effect of process parameters onto the granule and tablet properties. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/27449628/Continuous_melt_granulation:_Influence_of_process_and_formulation_parameters_upon_granule_and_tablet_properties_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(16)30327-7 DB - PRIME DP - Unbound Medicine ER -