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Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion.
Int J Pharm 2013; 455(1-2):159-68IJ

Abstract

Implementation of continuous manufacturing in the pharmaceutical industry requires tight process control. This study focuses on a PAT strategy for hot melt extrusion of vegetable calcium stearate (CaSt) as matrix carrier and paracetamol as active pharmaceutical ingredient (API). The extrusion was monitored using in-line near-infrared (NIR) spectroscopy. A NIR probe was located in the section between the extrusion screws and the die, using a novel design of the die channel. A chemometric model was developed based on premixes at defined concentrations and was implemented in SIPAT for real time API concentration monitoring. Subsequently, step experiments were performed for different API concentrations, screw speeds and screw designs. The predicted API concentration was in good agreement with the pre-set concentrations. The transition from one API plateau to another was a smooth curve due to the mixing behaviour of the extruder. The accuracy of the model was confirmed via offline HPLC analysis. The screw design was determined as the main influential factor on content uniformity (CU). Additionally the influence of multiple feeders had a significant impact on CU. The results demonstrate that in-line NIR measurements is a powerful tool for process development (e.g., mixing characterization), monitoring and further control strategies.

Authors+Show Affiliations

Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13/2, 8010 Graz, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23911343

Citation

Wahl, Patrick R., et al. "Inline Monitoring and a PAT Strategy for Pharmaceutical Hot Melt Extrusion." International Journal of Pharmaceutics, vol. 455, no. 1-2, 2013, pp. 159-68.
Wahl PR, Treffer D, Mohr S, et al. Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion. Int J Pharm. 2013;455(1-2):159-68.
Wahl, P. R., Treffer, D., Mohr, S., Roblegg, E., Koscher, G., & Khinast, J. G. (2013). Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion. International Journal of Pharmaceutics, 455(1-2), pp. 159-68. doi:10.1016/j.ijpharm.2013.07.044.
Wahl PR, et al. Inline Monitoring and a PAT Strategy for Pharmaceutical Hot Melt Extrusion. Int J Pharm. 2013 Oct 15;455(1-2):159-68. PubMed PMID: 23911343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion. AU - Wahl,Patrick R, AU - Treffer,Daniel, AU - Mohr,Stefan, AU - Roblegg,Eva, AU - Koscher,Gerold, AU - Khinast,Johannes G, Y1 - 2013/07/31/ PY - 2013/03/25/received PY - 2013/07/15/revised PY - 2013/07/17/accepted PY - 2013/8/6/entrez PY - 2013/8/6/pubmed PY - 2014/3/26/medline KW - API content KW - Hot melt extrusion KW - Near-infrared spectroscopy (NIRS) KW - Process Analytical Technology (PAT) KW - Quality control SP - 159 EP - 68 JF - International journal of pharmaceutics JO - Int J Pharm VL - 455 IS - 1-2 N2 - Implementation of continuous manufacturing in the pharmaceutical industry requires tight process control. This study focuses on a PAT strategy for hot melt extrusion of vegetable calcium stearate (CaSt) as matrix carrier and paracetamol as active pharmaceutical ingredient (API). The extrusion was monitored using in-line near-infrared (NIR) spectroscopy. A NIR probe was located in the section between the extrusion screws and the die, using a novel design of the die channel. A chemometric model was developed based on premixes at defined concentrations and was implemented in SIPAT for real time API concentration monitoring. Subsequently, step experiments were performed for different API concentrations, screw speeds and screw designs. The predicted API concentration was in good agreement with the pre-set concentrations. The transition from one API plateau to another was a smooth curve due to the mixing behaviour of the extruder. The accuracy of the model was confirmed via offline HPLC analysis. The screw design was determined as the main influential factor on content uniformity (CU). Additionally the influence of multiple feeders had a significant impact on CU. The results demonstrate that in-line NIR measurements is a powerful tool for process development (e.g., mixing characterization), monitoring and further control strategies. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/23911343/Inline_monitoring_and_a_PAT_strategy_for_pharmaceutical_hot_melt_extrusion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(13)00670-4 DB - PRIME DP - Unbound Medicine ER -