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Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal

The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), wh...

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Autores principales: Machado Cruz, Ricardo, Boleslavská, Tereza, Beránek, Josef, Tieger, Eszter, Twamley, Brendan, Santos-Martinez, Maria Jose, Dammer, Ondřej, Tajber, Lidia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464664/
https://www.ncbi.nlm.nih.gov/pubmed/32781726
http://dx.doi.org/10.3390/pharmaceutics12080741
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author Machado Cruz, Ricardo
Boleslavská, Tereza
Beránek, Josef
Tieger, Eszter
Twamley, Brendan
Santos-Martinez, Maria Jose
Dammer, Ondřej
Tajber, Lidia
author_facet Machado Cruz, Ricardo
Boleslavská, Tereza
Beránek, Josef
Tieger, Eszter
Twamley, Brendan
Santos-Martinez, Maria Jose
Dammer, Ondřej
Tajber, Lidia
author_sort Machado Cruz, Ricardo
collection PubMed
description The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and dissolution were performed. Evidence of the cocrystal formation was obtained from liquid-assisted grinding, but not neat grinding. An efficient method of the ITR–TER cocrystal formation was ball milling. The stoichiometry of the ITR–TER phase was 2:1 and the structure was stabilized by H-bonds. When comparing ITR–TER with other cocrystals, the intrinsic dissolution rates and powder dissolution profiles correlated with the aqueous solubility of the coformers. The rank order of the dissolution rates of the active pharmaceutical ingredient (API) from the cocrystals was ITR–oxalic acid > ITR–succinic acid > ITR–TER. Additionally, the ITR–TER cocrystal was stable in aqueous conditions and did not transform to the parent drug. In summary, this work presents another cocrystal of ITR that might be of use in pharmaceutical formulations.
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spelling pubmed-74646642020-09-04 Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal Machado Cruz, Ricardo Boleslavská, Tereza Beránek, Josef Tieger, Eszter Twamley, Brendan Santos-Martinez, Maria Jose Dammer, Ondřej Tajber, Lidia Pharmaceutics Article The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and dissolution were performed. Evidence of the cocrystal formation was obtained from liquid-assisted grinding, but not neat grinding. An efficient method of the ITR–TER cocrystal formation was ball milling. The stoichiometry of the ITR–TER phase was 2:1 and the structure was stabilized by H-bonds. When comparing ITR–TER with other cocrystals, the intrinsic dissolution rates and powder dissolution profiles correlated with the aqueous solubility of the coformers. The rank order of the dissolution rates of the active pharmaceutical ingredient (API) from the cocrystals was ITR–oxalic acid > ITR–succinic acid > ITR–TER. Additionally, the ITR–TER cocrystal was stable in aqueous conditions and did not transform to the parent drug. In summary, this work presents another cocrystal of ITR that might be of use in pharmaceutical formulations. MDPI 2020-08-06 /pmc/articles/PMC7464664/ /pubmed/32781726 http://dx.doi.org/10.3390/pharmaceutics12080741 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Machado Cruz, Ricardo
Boleslavská, Tereza
Beránek, Josef
Tieger, Eszter
Twamley, Brendan
Santos-Martinez, Maria Jose
Dammer, Ondřej
Tajber, Lidia
Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
title Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
title_full Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
title_fullStr Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
title_full_unstemmed Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
title_short Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal
title_sort identification and pharmaceutical characterization of a new itraconazole terephthalic acid cocrystal
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464664/
https://www.ncbi.nlm.nih.gov/pubmed/32781726
http://dx.doi.org/10.3390/pharmaceutics12080741
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