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Article

Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal

1
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland
2
Zentiva, k.s., U Kabelovny 130, 102 37 Prague, Czech Republic
3
Department of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague, Czech Republic
4
School of Medicine, Trinity College Dublin, Dublin 2, Ireland
5
School of Chemistry, Trinity College Dublin, Dublin 2, Ireland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(8), 741; https://doi.org/10.3390/pharmaceutics12080741
Received: 17 July 2020 / Revised: 30 July 2020 / Accepted: 31 July 2020 / Published: 6 August 2020
(This article belongs to the Special Issue Cocrystal Applications in Drug Delivery)
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. View Full-Text
Keywords: itraconazole; terephthalic acid; cocrystal; crystal structure; mechanochemistry; solid-state; thermal analysis; wettability; dissolution itraconazole; terephthalic acid; cocrystal; crystal structure; mechanochemistry; solid-state; thermal analysis; wettability; dissolution
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MDPI and ACS Style

Machado Cruz, R.; Boleslavská, T.; Beránek, J.; Tieger, E.; Twamley, B.; Santos-Martinez, M.J.; Dammer, O.; Tajber, L. Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal. Pharmaceutics 2020, 12, 741. https://doi.org/10.3390/pharmaceutics12080741

AMA Style

Machado Cruz R, Boleslavská T, Beránek J, Tieger E, Twamley B, Santos-Martinez MJ, Dammer O, Tajber L. Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal. Pharmaceutics. 2020; 12(8):741. https://doi.org/10.3390/pharmaceutics12080741

Chicago/Turabian Style

Machado Cruz, Ricardo, Tereza Boleslavská, Josef Beránek, Eszter Tieger, Brendan Twamley, Maria J. Santos-Martinez, Ondřej Dammer, and Lidia Tajber. 2020. "Identification and Pharmaceutical Characterization of a New Itraconazole Terephthalic Acid Cocrystal" Pharmaceutics 12, no. 8: 741. https://doi.org/10.3390/pharmaceutics12080741

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