Examinando por Autor "Vega, Daniel Roberto"

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    Characterization of the hydrochloride salt hemihydrate as a new salt of the antifungal agent tioconazole
    (Elsevier, 2023-03-14) Moroni, Aldana Beatriz; Pérez Mayoral, Elena; Lionello, Diego Fernando; Vega, Daniel Roberto; Kaufman, Teodoro Saúl; Calvo, Natalia Lorena
    Tioconazole 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.
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    Preparation and characterization of new salts of tioconazole. Comparison of their dissolution performance
    (Elsevier, 2024-01-23) Moroni, Aldana Beatriz; Pérez Mayoral, Elena; Lionello, Diego Fernando; Vega, Daniel Roberto; Kaufman, Teodoro Saúl; Calvo, Natalia Lorena
    Tioconazole is an effective antifungal agent with very low solubility in aqueous media, which limits its bioavailability and efficacy. Aiming to overcome the drug limitations by improving the solubility of this active pharmaceutical ingredient, solution precipitation techniques were employed to prepare four new crystalline salts, namely the mesylate, tosylate, maleate (1:1), and fumarate (1:1) hemihydrate. The thermal stabilities, dissolution properties, and structural characteristics of the solids were determined, and the study was extended to compare their properties with the already-known oxalate salt. The structural characterization of the new phases was carried out using a multi-method approach, which included thermal (differential scanning calorimetry and thermogravimetry), diffractometric (powder X-ray diffraction), and spectroscopic (near-infrared and mid-infrared) methodologies. The determination of the melting point of the salts confirmed the findings made by thermal methods. Functional characteristics of the salts, involving their intrinsic dissolution rates were also determined. It was found that the salts exhibited improved thermal stability and that the nature of the counterion modulated their dissolution characteristics. The salts displayed better intrinsic dissolution rates than the free base, to the point of being “highly soluble” according to the Biopharmaceutical Classification System. At pH 4.3, the sulfonic acid derivatives exhibited better dissolution rates than their carboxylic acid-derived counterparts, greatly improved regarding bare tioconazole. The results suggest that the salts have great potential to be used as replacements for the free base; in principle, careful salt selection may help to fulfill each solubility need for the different scenarios where the drug may be used.
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    Solid-state properties of Nifurtimox. Preparation, analytical characterization, and stability of an amorphous phase
    (Elsevier, 2023-01-13) Moroni, Aldana Beatriz; Pérez Mayoral, Elena; Lionello, Diego Fernando; Vega, Daniel Roberto; Kaufman, Teodoro Saúl; Calvo, Natalia Lorena
    Nifurtimox (NFX) is a nitrofuran derivative used to treat Chagas disease, a neglected disease caused by the protozoan Trypanosoma cruzi. The drug is very sparingly soluble in aqueous media and no other solid phases of NFX have been reported to date. The preparation of the amorphous mode of NFX is reported, as well as its characterization by hot stage microscopy, thermal (differential scanning calorimetry and thermogravimetric analysis), spectroscopic (solid state nuclear magnetic resonance, mid-infrared, and near-infrared), diffractometric and functional (powder dissolution rate) means. The stability of the new phase was investigated. This was characterized using thermal, spectroscopic, and diffractometric methods, finding out its spontaneous reversion to the crystalline state, as sign of instability. In addition, the amorphous material proved to be sensitive to temperature, pressure, and mechanical stress, all of which accelerated phase conversion. However, it was able to remain stable in a model polymeric amorphous solid dispersion with PEG 4000 for more than one month. An approach for monitoring the conversion of the amorphous phase to its crystalline counterpart under thermal stress by chemometric analysis of mid-infrared spectra at different temperatures is also disclosed.