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Downstream processing from hot-melt extrusion towards tablets: A quality by design approach.
Int J Pharm 2017; 531(1):235-245IJ

Abstract

Since the concept of continuous processing is gaining momentum in pharmaceutical manufacturing, a thorough understanding on how process and formulation parameters can impact the critical quality attributes (CQA) of the end product is more than ever required. This study was designed to screen the influence of process parameters and drug load during HME on both extrudate properties and tableting behaviour of an amorphous solid dispersion formulation using a quality-by-design (QbD) approach. A full factorial experimental design with 19 experiments was used to evaluate the effect of several process variables (barrel temperature: 160-200°C, screw speed: 50-200rpm, throughput: 0.2-0.5kg/h) and drug load (0-20%) as formulation parameter on the hot-melt extrusion (HME) process, extrudate and tablet quality of Soluplus®-Celecoxib amorphous solid dispersions. A prominent impact of the formulation parameter on the CQA of the extrudates (i.e. solid state properties, moisture content, particle size distribution) and tablets (i.e. tabletability, compactibility, fragmentary behaviour, elastic recovery) was discovered. The resistance of the polymer matrix to thermo-mechanical stress during HME was confirmed throughout the experimental design space. In addition, the suitability of Raman spectroscopy as verification method for the active pharmaceutical ingredient (API) concentration in solid dispersions was evaluated. Incorporation of the Raman spectroscopy data in a PLS model enabled API quantification in the extrudate powders with none of the DOE-experiments resulting in extrudates with a CEL content deviating>3% of the label claim. This research paper emphasized that HME is a robust process throughout the experimental design space for obtaining amorphous glassy solutions and for tabletting of such formulations since only minimal impact of the process parameters was detected on the extrudate and tablet properties. However, the quality of extrudates and tablets can be optimized by adjusting specific formulations parameters (e.g. drug load).

Authors+Show Affiliations

Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Department of Electronics and Information Systems (ELIS), Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28823887

Citation

Grymonpré, W, et al. "Downstream Processing From Hot-melt Extrusion Towards Tablets: a Quality By Design Approach." International Journal of Pharmaceutics, vol. 531, no. 1, 2017, pp. 235-245.
Grymonpré W, Bostijn N, Herck SV, et al. Downstream processing from hot-melt extrusion towards tablets: A quality by design approach. Int J Pharm. 2017;531(1):235-245.
Grymonpré, W., Bostijn, N., Herck, S. V., Verstraete, G., Vanhoorne, V., Nuhn, L., ... Vervaet, C. (2017). Downstream processing from hot-melt extrusion towards tablets: A quality by design approach. International Journal of Pharmaceutics, 531(1), pp. 235-245. doi:10.1016/j.ijpharm.2017.08.077.
Grymonpré W, et al. Downstream Processing From Hot-melt Extrusion Towards Tablets: a Quality By Design Approach. Int J Pharm. 2017 Oct 5;531(1):235-245. PubMed PMID: 28823887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downstream processing from hot-melt extrusion towards tablets: A quality by design approach. AU - Grymonpré,W, AU - Bostijn,N, AU - Herck,S Van, AU - Verstraete,G, AU - Vanhoorne,V, AU - Nuhn,L, AU - Rombouts,P, AU - Beer,T De, AU - Remon,J P, AU - Vervaet,C, Y1 - 2017/08/18/ PY - 2017/06/26/received PY - 2017/08/10/revised PY - 2017/08/12/accepted PY - 2017/8/22/pubmed PY - 2018/1/11/medline PY - 2017/8/22/entrez KW - Hot-melt extrusion (HME) KW - Principle component analysis (PCA) KW - Quality by design KW - Raman spectroscopy KW - Solid dispersion KW - Tablet quality KW - Tableting SP - 235 EP - 245 JF - International journal of pharmaceutics JO - Int J Pharm VL - 531 IS - 1 N2 - Since the concept of continuous processing is gaining momentum in pharmaceutical manufacturing, a thorough understanding on how process and formulation parameters can impact the critical quality attributes (CQA) of the end product is more than ever required. This study was designed to screen the influence of process parameters and drug load during HME on both extrudate properties and tableting behaviour of an amorphous solid dispersion formulation using a quality-by-design (QbD) approach. A full factorial experimental design with 19 experiments was used to evaluate the effect of several process variables (barrel temperature: 160-200°C, screw speed: 50-200rpm, throughput: 0.2-0.5kg/h) and drug load (0-20%) as formulation parameter on the hot-melt extrusion (HME) process, extrudate and tablet quality of Soluplus®-Celecoxib amorphous solid dispersions. A prominent impact of the formulation parameter on the CQA of the extrudates (i.e. solid state properties, moisture content, particle size distribution) and tablets (i.e. tabletability, compactibility, fragmentary behaviour, elastic recovery) was discovered. The resistance of the polymer matrix to thermo-mechanical stress during HME was confirmed throughout the experimental design space. In addition, the suitability of Raman spectroscopy as verification method for the active pharmaceutical ingredient (API) concentration in solid dispersions was evaluated. Incorporation of the Raman spectroscopy data in a PLS model enabled API quantification in the extrudate powders with none of the DOE-experiments resulting in extrudates with a CEL content deviating>3% of the label claim. This research paper emphasized that HME is a robust process throughout the experimental design space for obtaining amorphous glassy solutions and for tabletting of such formulations since only minimal impact of the process parameters was detected on the extrudate and tablet properties. However, the quality of extrudates and tablets can be optimized by adjusting specific formulations parameters (e.g. drug load). SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/28823887/Downstream_processing_from_hot_melt_extrusion_towards_tablets:_A_quality_by_design_approach_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(17)30784-6 DB - PRIME DP - Unbound Medicine ER -