Liquid API feeding in pharmaceutical HME: Novel options in solid dosage manufacturing.

Autor: Kuchler L; Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria., Spoerk M; Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13/3, 8010 Graz, Austria., Eder S; Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria., Doğan A; Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria., Khinast J; Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13/3, 8010 Graz, Austria., Sacher S; Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria. Electronic address: stephan.sacher@rcpe.at.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jan 25; Vol. 650, pp. 123690. Date of Electronic Publication: 2023 Dec 09.
DOI: 10.1016/j.ijpharm.2023.123690
Abstrakt: Hot melt extrusion (HME) is a common unit operation. It is broadly applicable in the pharmaceutical industry and can be implemented in a continuous manufacturing line. However, the conventional way of active pharmaceutical ingredient (API) feeding with a pre-blend consisting of a powdered API and a polymer does not allow the flexibility and agility to adjust the process parameters, which is generally an essential part of continuous manufacturing. In addition, this method of API feeding may result in the segregation of the individual powder components or agglomeration of highly cohesive materials, leading to an inhomogeneous API content in the extrudates, especially at low doses. In this study, the universal applicability of liquid side feeding in pharmaceutical HME was demonstrated using various APIs suspended or dissolved in water and fed as suspension or undersaturated, supersaturated, and highly concentrated solutions into anterior parts of the extruder. The extrudates were characterized in terms of their API content, residual moisture content, and solid-state of the API embedded in the polymer. The results show that a uniform API content without major deviations can be obtained via this method. Furthermore, the residual moisture content of the extrudates was low enough to have no significant influence on further processing of the final dosage form. In summary, this advanced way of feeding allows an accurate, flexible, and agile feeding of APIs, facilitating the production of personalized final dosage forms and a novel option to link the manufacturing of the drug substance and the drug product.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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