Characterization of the hydrochloride salt hemihydrate as a new salt of the antifungal agent tioconazole

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dc.citation.titleInternational Journal of Pharmaceutics
dc.citation.volume637
dc.creatorMoroni, Aldana Beatriz
dc.creatorPérez Mayoral, Elena
dc.creatorLionello, Diego Fernando
dc.creatorVega, Daniel Roberto
dc.creatorKaufman, Teodoro Saúl
dc.creatorCalvo, Natalia Lorena
dc.date.accessioned2024-09-27T14:29:46Z
dc.date.available2024-09-27T14:29:46Z
dc.date.issued2023-03-14
dc.description.abstractTioconazole is an effective antifungal agent, which has a very low solubility in aqueous media, that limits its bioavailability and efficacy. In an effort to overcome the drug limitations by improving its solubility, the hydrochloride salt was prepared in methanolic 1 M HCl and obtained as the hemihydrate, as demonstrated by elemental analysis. Single crystals were grown by slow evaporation from an aqueous 1 M HCl solution and their structure was determined using single-crystal X-ray diffraction at 302 K. The structures resulting from dehydration and further rehydration were also assessed, at 333 and 283 K, respectively. The morphology of the crystal, which exhibited birefringence under polarized light, was verified by hot stage microscopy. The solid was characterized by additional means, including thermal analysis (melting point, differential scanning calorimetry and thermogravimetry), spectroscopic methods (mid infrared, near infrared, 1H, 13C and 15N nuclear magnetic resonance in solution, as well as 13C and 15N solid state with spinning at the magic angle) and X-ray diffraction techniques. Functional evaluation tests, including the intrinsic dissolution rate and the dissolution of powders were also performed. In the intrinsic dissolution rate test, the salt proved to dissolve over 2000 times faster than tioconazole. The results suggest that the new salt has physicochemical and performance properties which may support its use as a replacement of the free base in certain applications, especially where improved dissolution rate, solubility or bioavailability of the drug would be desired.
dc.description.filFil: Moroni, Aldana Beatriz. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET). Área de Análisis de Medicamentos; Argentina.
dc.description.filFil: Pérez Mayoral, Elena. Universidad Nacional de Educación a Distancia. Departamento de Química Inorgánica y Química Técnica; España.
dc.description.filFil: Lionello, Diego Fernando. Universidad Nacional General San Martín. Instituto de Tecnología Sabato (CNEA); Argentina.
dc.description.filFil: Lionello, Diego Fernando. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes. Departamento de Física de la Materia Condensada (CONICET/UNSaM); Argentina.
dc.description.filFil: Vega, Daniel Roberto. Universidad Nacional General San Martín. Escuela de Ciencia y Tecnologia (CNEA); Argentina.
dc.description.filFil: Vega, Daniel Roberto. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes. Departamento de Física de la Materia Condensada (CONICET/UNSaM); Argentina.
dc.description.filFil: Kaufman, Teodoro Saúl. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET). Área de Análisis de Medicamentos; Argentina.
dc.description.filFil: Calvo, Natalia Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET). Área de Análisis de Medicamentos; Argentina.
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET): PUE IQUIR 2016, PIP 2021-0765
dc.description.sponsorshipAgencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Agencia I+D+i): PICT 2019-1155
dc.description.sponsorshipAgencia Santafesina de Ciencia Tecnología e Innovación (ASaCTeI): IO2019-302, BMG-N-2021-134
dc.description.sponsorshipFundación Carolina
dc.description.versionpeerreviewed
dc.format.extent1-9
dc.identifier.citationMoroni, A. B., Pérez Mayoral, E., Lionello, D. F., Vega, D. R., Kaufman, T. S. and Calvo, N. L. (2023). Characterization of the hydrochloride salt hemihydrate as a new salt of the antifungal agent tioconazole. International Journal of Pharmaceutics, 637. https://doi.org/10.1016/j.ijpharm.2023.122869
dc.identifier.e-issn1873-3476
dc.identifier.issn0378-5173
dc.identifier.urihttps://hdl.handle.net/2133/27869
dc.language.isoen
dc.publisherElsevier
dc.relation.publisherversionhttps://doi.org/10.1016/j.ijpharm.2023.122869
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S0378517323002892?via%3Dihub
dc.rightsembargoedAccess
dc.rights.holderMoroni, Aldana Beatriz
dc.rights.holderPérez Mayoral, Elena
dc.rights.holderLionello, Diego Fernando
dc.rights.holderVega, Daniel Roberto
dc.rights.holderKaufman, Teodoro Saúl
dc.rights.holderCalvo, Natalia Lorena
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.holderElsevier
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectIntrinsic dissolution
dc.subjectSalt formation
dc.subjectSolid-state characterization
dc.subjectTioconazole hydrochloride hemihydrate
dc.subjectThermal methods
dc.subjectVibrational and NMR spectroscopies
dc.subjectX-ray diffractometry and crystal structure
dc.titleCharacterization of the hydrochloride salt hemihydrate as a new salt of the antifungal agent tioconazole
dc.typearticulo
dc.type.versionacceptedVersion

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