Application of thermal analysis to the study of anti-tuberculosis drug compatibility. Part 1

Lavor, Edilene P.; Freire, Fátima Duarte; Aragão, Cícero Flávio Soares; Raffin, Fernanda Nervo; Moura, Túlio Flávio Accioly de Lima e

doi:10.1007/s10973-011-1770-8

Cited by 22 publications

(6 citation statements)

References 22 publications

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“…As we can observe in Figure 2, the thermogram of the initial compounds present peaks of endothermic events, in some of them we observe two peaks which could indicate different transition stages between the crystalline and amorphous phases [6,8,15,16,17]. THEDES with ethambutol in liquid phase does not present peaks at endothermic stage.…”

Section: Resultsmentioning

confidence: 84%

Properties of Therapeutic Deep Eutectic Solvents of l-Arginine and Ethambutol for Tuberculosis Treatment

2018

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The treatment for tuberculosis infection usually involves a prolonged regimen of multiple antibacterial drugs, which might lead to various secondary effects. For preventing drug resistance and side-effects of anti-tuberculosis drugs, new methods for improving the bioavailability of APIs were investigated. The strategy proposed consists of the preparation of therapeutic deep eutectic solvents (THEDES), that incorporate l-arginine and ethambutol. The eutectic mixtures were prepared by mixing the components at a certain molar ratio, until a clear liquid solution was formed. The prepared mixtures were characterized by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and nuclear magnetic resonance spectroscopy (1H and 13C-NMR). The solubility and permeability of the drugs when they are in the THEDES form was evaluated at 37 °C, in phosphate buffered saline (PBS). Solubility studies showed an increase of the solubility of ethambutol when incorporated in the eutectic system. The cytotoxicity was evaluated using a model cell line (Caco-2), comparing the cytotoxicity of the API incorporated in the eutectic system. We observed that the cell viability in the THEDES was affected by the presence of citric acid, and higher cytotoxicity values were observed. Nonetheless, these findings do not compromise the possibility to use these systems as new delivery systems for ethambutol and arginine.

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Section: Resultsmentioning

confidence: 84%

Properties of Therapeutic Deep Eutectic Solvents of l-Arginine and Ethambutol for Tuberculosis Treatment

2018

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“…According to Cides et al,41 the absence of melting point in DSC scans may indicate the component has remained in its amorphous form. INH-linked copper(II) complexes had a melting temperature of 170°C–173°C,42 however, it was not observed in the scans, which suggested that INH was inserted into the copper(II) complexes.…”

Section: Resultsmentioning

confidence: 94%

Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against <em>Mycobacterium tuberculosis</em>

Sato

Oshiro

Machado

et al. 2017

DDDT

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Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Cessation of treatment before the recommended conclusion may lead to the emergence of multidrug-resistant strains. The aim of this study was to develop nanostructured lipid carriers (NLCs) for use in the treatment of M. tuberculosis. The NLCs comprised the following lipid phase: 2.07% polyoxyethylene 40 stearate, 2.05% caprylic/capric triglyceride, and 0.88% polyoxyl 40 hydrogenated castor oil; the following aqueous phase: 3.50% poloxamer 407 (F1–F6), and 0.50% cetyltrimethylammonium bromide (F7–F12); and incorporated the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2), and [Cu(NCO)2(INH)2]·4H2O (3) to form compounds F11.1, F11.2, and F11.3, respectively. The mean diameter of F11, F11.1, F11.2, and F11.3 ranged from 111.27±21.86 to 134.25±22.72 nm, 90.27±12.97 to 116.46±9.17 nm, 112.4±10.22 to 149.3±15.82 nm, and 78.65±6.00 to 122.00±8.70 nm, respectively. The polydispersity index values for the NLCs ranged from 0.13±0.01 to 0.30±0.09. The NLCs showed significant changes in zeta potential, except for F11.2, with F11, F11.1, F11.2, and F11.3 ranging from 18.87±4.04 to 23.25±1.13 mV, 17.03±1.77 to 21.42±1.87 mV, 20.51±1.88 to 22.60±3.44 mV, and 17.80±1.96 to 25.25±7.78 mV, respectively. Atomic force microscopy confirmed the formation of nanoscale spherical particle dispersions by the NLCs. Differential scanning calorimetry determined the melting points of the constituents of the NLCs. The in vitro activity of copper(II) complex-loaded NLCs against M. tuberculosis H37Rv showed an improvement in the anti-TB activity of 55.4, 27.1, and 41.1 times the activity for complexes 1, 2, and 3, respectively. An in vivo acute toxicity study of complex-loaded NLCs demonstrated their reduced toxicity. The results suggest that NLCs may be a powerful tool to optimize the activity of copper(II) complexes against M. tuberculosis.

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“…The specific volume of different polymorphs of PZA in the literature is shown in Table 2. Lavor et al, 2012) 420.4(5) 13.3(2) 5 ) 420.65 11.35 5 (Baaklini et al, 2015 d®g 408(5) 17(2) 10 (Castro et al, 2009) 404.35 13.5 5 (Cherukuvada et al, 2010) d®a 395(1) ∆H > 0 b 10 (Castro et al, 2009) b®g 368.15 ∆H > 0 b 10 (Castro et al, 2009) 372.55 6.3 5 (Cherukuvada et al, 2010) PZA®vap 829(18) c (Ribeiro da Silva et al, 2005) a®vap 915(13) d (Blokhina et al, 2015a) a®vap 715(44) e (Negoro, 1959;Negoro, 1960) a Values from the literature reported in °C or in J mol -1 are adjusted by adding 273.15 K or are divided by 123.11 g mol -1 , respectively; an average value is used in this table when multiple values have been reported in the same paper; values are rounded to the number of reported digits in the respective reference. b Enthalpy values have not been mentioned in the reference (Castro et al, 2009), but DSC curves in the figures indicate endothermic transitions with increasing temperature.…”

Section: Literature Data On the Phase Behavior Of Pyrazinamidementioning

confidence: 99%

The phase relationship between the pyrazinamide polymorphs α and γ

Gbabode

Tamarit

et al. 2020

International Journal of Pharmaceutics

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Pyrazinamide is an active pharmaceutical compound for the treatment of tuberculosis. It possesses at least four crystalline polymorphs. Polymorphism may cause solubility problems as the case of ritonavir has clearly demonstrated; however, polymorphs also provide opportunities to improve pharmaceutical formulations, in particular if the stable form is not very soluble. The four polymorphs of pyrazinamide constitute a rich system to investigate the usefulness of metastable forms and their stabilization. However, despite the existence of a number of papers on the polymorphism of pyrazinamide, well-defined equilibrium conditions between the polymorphs appear to be lacking. This paper focusses on the phase behavior of the so-called a and g polymorphs of pyrazinamide, its liquid phase and vapor phase. The melting points and enthalpies of both solid phases have been determined. The equilibrium temperature between a and g was experimentally found at 392(1) K. Moreover, vapor pressures and solubilities of both phases have been determined, clearly indicating that form a is the more stable form at room temperature. High-pressure thermal analysis and the topological pressure-temperature phase diagram demonstrate that the g form is stabilized by pressure and becomes stable at room temperature under a pressure of 260 MPa. File list (2) download file view on ChemRxiv pyrazinamidePhaseBehavior-alpha-gamma-OA.pdf (1.93 MiB) download file view on ChemRxiv Supplementary Materials-OA.pdf (344.86 KiB)

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Application of thermal analysis to the study of anti-tuberculosis drug compatibility. Part 1

Cited by 22 publications

References 22 publications

Properties of Therapeutic Deep Eutectic Solvents of l-Arginine and Ethambutol for Tuberculosis Treatment

Properties of Therapeutic Deep Eutectic Solvents of l-Arginine and Ethambutol for Tuberculosis Treatment

Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against <em>Mycobacterium tuberculosis</em>

The phase relationship between the pyrazinamide polymorphs α and γ

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