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Tytuł:
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Development of a digital twin of a tablet that mimics a real solid dosage form: Differences in the dissolution profile in conventional mini-USP II and a biorelevant colon model.
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Autorzy:
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Schütt M; School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Stamatopoulos K; School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Biopharmaceutics, Pharmaceutical Development, PDS, MST, RD Platform Technology & Science, GSK, David Jack Centre, Park Road, Ware, Hertfordshire SG12 0DP, United Kingdom.
Batchelor HK; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
Simmons MJH; School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Alexiadis A; School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. Electronic address: .
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Źródło:
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European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2022 Dec 01; Vol. 179, pp. 106310. Date of Electronic Publication: 2022 Oct 18.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Amsterdam : Elsevier Science B.V
Original Publication: Amsterdam ; New York : Elsevier, c1993-
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MeSH Terms:
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Hydrodynamics*
Colon*
Humans ; Solubility ; Tablets ; Drug Liberation
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Grant Information:
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MC_PC_18040 United Kingdom MRC_ Medical Research Council
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Contributed Indexing:
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Keywords: Colon, mini-USP II; Digital twin; Dissolution profile; Mathematical modelling; Smoothed Particle Hydrodynamics (SPH)
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Substance Nomenclature:
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0 (Tablets)
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Entry Date(s):
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Date Created: 20221020 Date Completed: 20221107 Latest Revision: 20230322
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Update Code:
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20240105
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DOI:
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10.1016/j.ejps.2022.106310
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PMID:
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36265815
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The performance of colon-targeted solid dosage forms is commonly assessed using standardised pharmacopeial dissolution apparatuses like the USP II or the miniaturised replica, the mini-USP II. However, these fail to replicate the hydrodynamics and shear stresses in the colonic environment, which is crucial for the tablet's drug release process. In this work, computer simulations are used to create a digital twin of a dissolution apparatus and to develop a method to create a digital twin of a tablet that behaves realistically. These models are used to investigate the drug release profiles and shear rates acting on a tablet at different paddle speeds in the mini-USP II and biorelevant colon models to understand how the mini-USP II can be operated to achieve more realistic (i.e., in vivo) hydrodynamic conditions. The behaviour of the tablet and the motility patterns used in the simulations are derived from experimental and in vivo data, respectively, to obtain profound insights into the tablet's disintegration/drug release processes. We recommend an "on-off" operating mode in the mini-USP II to generate shear rate peaks, which would better reflect the in vivo conditions of the human colon instead of constant paddle speed.
Competing Interests: Declaration of Competing Interest The authors have declared that no competing interests exist.
(Copyright © 2022. Published by Elsevier B.V.)