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Process design and control of a twin screw hot melt extrusion for continuous pharmaceutical tamper-resistant tablet production.
Eur J Pharm Sci 2016; 87:14-21EJ

Abstract

Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most efficient production technique. The focus of this study is thus to evaluate the manufacturability of the HME process for tamper-resistant formulations. Parameters such as the specific mechanical energy (SME), as well as the melt pressure and its standard deviation, are important and will be discussed in this study. In the first step, the existing process data are analyzed by means of multivariate data analysis. Key critical process parameters such as feed rate, screw speed, and the concentration of the API in the polymers are identified, and critical quality parameters of the tablet are defined. In the second step, a relationship between the critical material, product and process quality attributes are established by means of Design of Experiments (DoEs). The resulting SME and the temperature at the die are essential data points needed to indirectly qualify the degradation of the API, which should be minimal. NIR-spectroscopy is used to monitor the material during the extrusion process. In contrast to most applications in which the probe is directly integrated into the die, the optical sensor is integrated into the cooling line of the strands. This saves costs in the probe design and maintenance and increases the robustness of the chemometric models. Finally, a process measurement system is installed to monitor and control all of the critical attributes in real-time by means of first principles, DoE models, soft sensor models, and spectroscopic information. Overall, the process is very robust as long as the screw speed is kept low.

Authors+Show Affiliations

Global Product Supply - Transfer & Strategy, Grünenthal GmbH, Zieglerstr. 6, 52078 Aachen, Germany.Global Product Supply - Transfer & Strategy, Grünenthal GmbH, Zieglerstr. 6, 52078 Aachen, Germany.STZ Prozesskontrolle und Datenanalyse, Herderstr. 47, 72762 Reutlingen, Germany.STZ Prozesskontrolle und Datenanalyse, Herderstr. 47, 72762 Reutlingen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26386253

Citation

Baronsky-Probst, J, et al. "Process Design and Control of a Twin Screw Hot Melt Extrusion for Continuous Pharmaceutical Tamper-resistant Tablet Production." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 87, 2016, pp. 14-21.
Baronsky-Probst J, Möltgen CV, Kessler W, et al. Process design and control of a twin screw hot melt extrusion for continuous pharmaceutical tamper-resistant tablet production. Eur J Pharm Sci. 2016;87:14-21.
Baronsky-Probst, J., Möltgen, C. V., Kessler, W., & Kessler, R. W. (2016). Process design and control of a twin screw hot melt extrusion for continuous pharmaceutical tamper-resistant tablet production. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 87, pp. 14-21. doi:10.1016/j.ejps.2015.09.010.
Baronsky-Probst J, et al. Process Design and Control of a Twin Screw Hot Melt Extrusion for Continuous Pharmaceutical Tamper-resistant Tablet Production. Eur J Pharm Sci. 2016 May 25;87:14-21. PubMed PMID: 26386253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Process design and control of a twin screw hot melt extrusion for continuous pharmaceutical tamper-resistant tablet production. AU - Baronsky-Probst,J, AU - Möltgen,C-V, AU - Kessler,W, AU - Kessler,R W, Y1 - 2015/09/18/ PY - 2015/07/31/received PY - 2015/09/05/revised PY - 2015/09/15/accepted PY - 2015/9/20/entrez PY - 2015/9/20/pubmed PY - 2017/3/30/medline KW - Continuous production KW - Hot melt extrusion KW - Manufacturability KW - Process analytical technologies (PAT) KW - Quality by design (QbD) SP - 14 EP - 21 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 87 N2 - Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most efficient production technique. The focus of this study is thus to evaluate the manufacturability of the HME process for tamper-resistant formulations. Parameters such as the specific mechanical energy (SME), as well as the melt pressure and its standard deviation, are important and will be discussed in this study. In the first step, the existing process data are analyzed by means of multivariate data analysis. Key critical process parameters such as feed rate, screw speed, and the concentration of the API in the polymers are identified, and critical quality parameters of the tablet are defined. In the second step, a relationship between the critical material, product and process quality attributes are established by means of Design of Experiments (DoEs). The resulting SME and the temperature at the die are essential data points needed to indirectly qualify the degradation of the API, which should be minimal. NIR-spectroscopy is used to monitor the material during the extrusion process. In contrast to most applications in which the probe is directly integrated into the die, the optical sensor is integrated into the cooling line of the strands. This saves costs in the probe design and maintenance and increases the robustness of the chemometric models. Finally, a process measurement system is installed to monitor and control all of the critical attributes in real-time by means of first principles, DoE models, soft sensor models, and spectroscopic information. Overall, the process is very robust as long as the screw speed is kept low. SN - 1879-0720 UR - https://www.unboundmedicine.com/medline/citation/26386253/Process_design_and_control_of_a_twin_screw_hot_melt_extrusion_for_continuous_pharmaceutical_tamper_resistant_tablet_production_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(15)30018-X DB - PRIME DP - Unbound Medicine ER -