Automated extrusion-based dispensing: Personalized dosing and quality control of clopidogrel tablets for pediatric care.

Autor: Shokraneh F; Pharmaceutical Sciences Laboratory, Science and Engineering, Åbo Akademi University, BioCity, Tykistökatu 6A, Turku FI-20520, Finland; CurifyLabs Oy, Salmisaarenaukio 1, Helsinki FI-00180, Finland. Electronic address: farnaz.shokraneh@abo.fi., Filppula AM; Pharmaceutical Sciences Laboratory, Science and Engineering, Åbo Akademi University, BioCity, Tykistökatu 6A, Turku FI-20520, Finland., Tornio A; Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, Turku FI-20520, Finland; Unit of Clinical Pharmacology, Turku University Hospital, Kiinamyllynkatu 10, Turku 20520, Finland., Aruväli J; Department of Geology, University of Tartu, Institute of Ecology and Earth Sciences, Ravila 14a, Tartu 50411, Estonia., Paaver U; Faculty of Medicine, Tartu University, Institute of Pharmacy, Nooruse 1, Tartu EE-50411, Estonia., Topelius NS; Pharmaceutical Sciences Laboratory, Science and Engineering, Åbo Akademi University, BioCity, Tykistökatu 6A, Turku FI-20520, Finland; CurifyLabs Oy, Salmisaarenaukio 1, Helsinki FI-00180, Finland.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2024 Nov 19; Vol. 204, pp. 106967. Date of Electronic Publication: 2024 Nov 19.
DOI: 10.1016/j.ejps.2024.106967
Abstrakt: The exploration of three-dimensional (3D) printing inspired technologies in pharmaceutical compounding reveals a promising frontier in personalized medicine manufacture. This study focuses on the development of clopidogrel bisulphate tablets, with doses ranging from 2 mg to 20 mg per tablet, suitable for pediatric use. The study explored a semi-solid extrusion-based deposition technology already being used in compounding pharmacies across several European locations. The investigation explored various properties of two formulations of 1 % and 2 % clopidogrel gel tablets, with a specific focus on mass variation, drug content uniformity, in vitro drug release profiles, disintegration time, and stability. The mean weights of the smallest printed 200 mg tablets with 1 % and 2 % clopidogrel concentrations were 199.1 ± 4.6 mg and 201.0 ± 3.2 mg, respectively. For the largest printed 500 mg tablets with 1 % and 2 % concentrations, the mean weights were 499.3 ± 7.7 mg and 501.7 ± 6.5 mg, respectively. The mean clopidogrel content uniformity for 1 % clopidogrel 200 mg and 500 mg tablets were 102.0 ± 1.8 %and 96.6 ± 2.6 %, respectively, and for 2 % clopidogrel 200 mg and 500 mg were 102.6 ± 3.9 % and 101.2 ± 1.6 %, respectively, well within the acceptable acceptance value (AV) range of 3 to 12. Both 1 % and 2 % formulations of clopidogrel tablets exhibited rapid drug release, meeting the USP pharmacopeial target of 85 % release in 15 min. All tablet sizes formulated at 1 % and 2 % concentrations met specified disintegration specifications. The stability assessment over three months revealed consistent pH values and assay results within target specifications for both clopidogrel formulations (93.5 % for 1 % formulation and 93.6 % for 2 % formulation). At three months, X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) results demonstrated stability in clopidogrel tablets. In conclusion, a comprehensive evaluation of our developed clopidogrel tablets demonstrate their suitability for clinical use in an extemporaneous setting using the presented semi-solid extrusion-based automation technology.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. CurifyLabs provided the materials, equipment, and PharmaPrinter for this study. Additionally, F.S. and N.S.T. are employed by CurifyLabs, and their roles influenced the research outcomes and manuscript preparation as follows: • Role in Planning Tests: CurifyLabs contributed to the planning and design of the experiments, ensuring that the methodologies employed were robust and aligned with industry standards. • Interpretation of Data: CurifyLabs provided expertise in the interpretation of data, offering insights into the results based on their extensive experience in pharmaceutical development. We acknowledge that the work utilizes commercialized technology, and the founders of this technology were involved in financing and conducting the research, as well as interpreting the results. We believe this collaboration enhances the rigor and relevance of the findings.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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