The use of ultrasound in the crystallization process of an active pharmaceutical ingredient

Majal Belca, Lucija (author), Ručigaj, Aleš (author), Teslič, Dušan (author), Krajnc, Matjaž (author)

In this research, ultrasound was used in the crystallization process as an alternative to conventional spontaneous crystallization and seeding crystallization. The study was implemented on an active pharmaceutical ingredient ticagrelor, where the influence of ultrasound on its physical properties was evaluated. Process parameters of spontaneous crystallization, seeding crystallization and ultrasound-assisted crystallization were extensively studied while the pros and cons of each were adequately exposed. Compared to spontaneous crystallization and seeding crystallization ultrasound-assisted crystallization has significantly improved fundamental crystallization parameters: nucleation, the growth of crystals and filtration time. At the same time, the tendency of particles to agglomerate was reduced, which lead to the avoidance of energy and time-consuming process of final product deagglomeration, often problematic in conventional crystallization. In addition, different physical properties of ticagrelor were reached and evaluated, for instance, morphology, particle size distribution and different polymorphic forms. Polymorphic forms I, II and III were efficiently produced in a repeatable, robust and optimal way. Ultrasound-assisted crystallization was proved to have a beneficial effect on the crystallization process of API, even on the industrial scale, and can successfully replace spontaneous crystallization and seeding crystallization.

• Language: English
• Keywords: crystallization, ultrasound, active pharmaceutical ingredient, ticagrelor, physical properties
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2019
• Number of pages: Str. 1-10
• Numbering: Vol. 58, art. 104642
• PID: 20.500.12556/RUL-108115
• UDC: 66.09
• ISSN on article: 1350-4177
• DOI: 10.1016/j.ultsonch.2019.104642
• COBISS.SI-ID: 1538246083

Copyright

V članku navedeno: "© 2019 Elsevier B.V. All rights reserved." Na pristajalni strani članka navedeno: "Under a Creative Commons license"; s povezavo https://creativecommons.org/licenses/by-nc-nd/4.0/. (18. 3. 2021) Na pristajalni strani članka tudi povezava "Get rights and content", kjer navedeno tudi: "This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed." (https://s100.copyright.com/AppDispatchServlet?publisherName=ELS&contentID=S1350417719306820&orderBeanReset=true, 16. 3. 2021)

• Publication date in RUL: 18.06.2019

Record is a part of a journal

• Title: Ultrasonics Sonochemistry
• Shortened title: Ultrason. sonochem.
• Publisher: Butterworth-Heinemann, Elsevier Science
• ISSN: 1350-4177
• COBISS.SI-ID: 707668

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
• Licensing start date: 18.06.2019

Secondary language

• Language: Slovenian
• Keywords: kristalizacija, ultrazvok, aktivna farmacevtska sestavina, inhibitor ticagrelor, fizikalne lastnosti

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Lek Pharmaceuticals d.d.