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dc.contributor.author
Salazar Rojas, Duvernis Maria
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dc.contributor.author
Kaufman, Teodoro Saul
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dc.contributor.author
Maggio, Ruben Mariano
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dc.date.available
2021-12-13T18:48:16Z
dc.date.issued
2021-04
dc.identifier.citation
Salazar Rojas, Duvernis Maria; Kaufman, Teodoro Saul; Maggio, Ruben Mariano; A comprehensive approach toward concomitant triclabendazole polymorphism in pharmaceutical products; Elsevier; Journal of Drug Delivery Science and Technology; 62; 4-2021; 1-10
dc.identifier.issn
1773-2247
dc.identifier.uri
http://hdl.handle.net/11336/148652
dc.description.abstract
Triclabendazole (TCB) is a highly effective and low-cost anti-parasitic active pharmaceutical ingredient (API) used in the treatment of fascioliasis, a neglected tropical disease caused by Fasciola hepatica. It belongs to Class II/IV in the Biopharmaceutics Classification System, where API dissolution results in the limiting step for its absorption. TCB exhibits tautomeric and conformational polymorphism, where Form I contains different conformations of tautomer A, and Form II is a 1:1 conglomerate of tautomers A and B, each in a single conformation. Since both forms may precipitate concomitantly during the preparation of the API, the control of polymorphic quality is critical for this anti-parasitic agent. A comprehensive approach was developed to address the determination of the polymorphic quality of drug-products when pure solid forms are not available, such as the case of concomitant crystallization of TCB I and II. First, both solid forms of the drug were isolated and characterized (digital optical microscopy, differential scanning calorimetry, hot stage microscopy, mid-infrared, near-infrared and solid-state 13C nuclear magnetic resonance). Next, lab-scale crystallization of Forms I and II was optimized, following a smart approach (green solvent and robust procedures), in order to obtain standards for calibration. A strategy based on NIR spectroscopy coupled to PLS was developed and validated to assess the polymorphic composition of drug-products. The new method was successfully applied to formulated products. The intrinsic dissolution rate of the pure forms demonstrated that Form II dissolves up to 60% faster than Form I, reinforcing the need for polymorphic control to assure the lot-to-lot equivalence. Thus, NIR-PLS emerges as a unique tool able to control the risk of polymorphic changes and their impact on bioavailability in formulated products.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
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dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CONCOMITANT POLYMORPHISM
dc.subject
CONCOMITANT POLYMORPHS
dc.subject
DISSOLUTION
dc.subject
DSC AND SSNMR
dc.subject
NIR-PLS
dc.subject
SOLID-STATE CHARACTERIZATION
dc.subject
TRICLABENDAZOLE
dc.subject
VIBRATIONAL SPECTROSCOPY
dc.subject.classification
Química Analítica
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dc.subject.classification
Ciencias Químicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
A comprehensive approach toward concomitant triclabendazole polymorphism in pharmaceutical products
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-12-03T21:36:33Z
dc.journal.volume
62
dc.journal.pagination
1-10
dc.journal.pais
Países Bajos
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dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Salazar Rojas, Duvernis Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
dc.description.fil
Fil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
dc.description.fil
Fil: Maggio, Ruben Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
dc.journal.title
Journal of Drug Delivery Science and Technology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1773224721000666
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.jddst.2021.102386
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