Assessing Drug-Excipient Interactions in the Formulation of Isoniazid Tablets

Wollinger, Wagner; Silva, Raphael A. da; Nóbrega, Armi Wanderley da; Lopes, Rosângela S. C.; Lopes, Claudio C.; Slana, Glaucia Barbosa Candido Alves

doi:10.5935/0103-5053.20150334

Cited by 2 publications

(1 citation statement)

References 9 publications

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“…In the chromatogram illustrated in Figure , 5-MeOT appeared as two split peaks ( R t = 2.28 and 2.93 min), sharing the same UV profile and m / z value [M + H] + = 191; one possible cause of this peak fragmentation is a difference in the elution strength between the diluent and the mobile phase (see Figure S3 and refs and for similar peak splitting).…”

Section: Resultsmentioning

confidence: 86%

Design, Synthesis, and Biological Activity of Hydrogen Peroxide Responsive Arylboronate Melatonin Hybrids

Bedini

Fraternale

Crinelli

et al. 2018

Chem. Res. Toxicol.

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Stimulus-responsive cleavage reactions have found broad use to direct drug release at a particular target disease area. Increased levels of reactive oxygen species (ROS) have been associated with the development and progression of cancer and several other disease states, motivating the development of drug conjugates that can undergo a chemoselective ROS-triggered release. Melatonin (MLT) and the reactive electrophile p-benzoquinone methide (p-QM) have evidenced either cytoprotective or cytotoxic effects in biological systems, depending on the dose, cellular targets, and time of exposure. In this study, we report the synthesis and biological activity of two MLT derivatives linked to ROS-responsive arylboronate triggers (P1 and P2), which can be activated by endogenously generated hydrogen peroxide (H2O2) to release MLT, or 5-methoxytryptamine (5-MeOT), and p-QM-intermediates. Their H2O2-induced activation mechanism was studied by HPLC-DAD-MS. P1, which rapidly releases MLT and p-QM, was able to strongly induce the Nrf2 antioxidant signaling pathway, but was ineffective to provide protection against H2O2-mediated oxidative damage. By contrast, P1 exhibited strong toxic effects in HeLa cancer cells, without causing significant toxicity to normal NCTC-2544 cells. Similar, although more limited, effects were exerted by P2. In both cases, cytotoxicity was accompanied by depletion of cellular glutathione (GSH), probably as a consequence of p-QM release, and increased ROS levels. A role for MLT in toxicity was also observed, suggesting that the P1 released products, MLT and p-QM, contributed additively to promote cell death.

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Section: Resultsmentioning

confidence: 86%

Design, Synthesis, and Biological Activity of Hydrogen Peroxide Responsive Arylboronate Melatonin Hybrids

Bedini

Fraternale

Crinelli

et al. 2018

Chem. Res. Toxicol.

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The use of photogenerated iodine for the determination of isoniazid in solid dosage formulation

Turusova

Насакин

Lyshchikov

2021

Zavod. lab., Diagn. mater.

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A shot cut method for the determination of isoniazid in a solid dosage formulation (DF) has been developed. The method is based on isoniazid titration with a solution of photogenerated iodine obtained as a result of irradiation of an auxiliary solution containing potassium iodide, a mixture of sensitizers (sodium eosinate, fluorescein, auramine taken in a molar ratio of 1:1:1) and phosphate buffer solution (pH 7.5). Since the titrant content in the cell was controlled using the voltammetric method (amperometric titration with two polarized electrodes), the interaction of a physiologically active compound with the latter was accompanied by a decrease in the amount of titrant in the cell and, hence, in the current in amperometric circuit. Stabilization of the current in the circuit of the amperometric setup indicated the completeness of the reaction, and, therefore, provided estimation of the content of a physiologically active compound in the dosage formulation. Further irradiation of the solution and measurement of the generation time required to replenish the loss of titrant in the cell also made it possible to regulate the content of isoniazid in the preparation. The technique was tested on the samples of solid dosed formulations. It was shown that the components of the tablet mass (calcium stearate monohydrate, polysorbate, crospovidone and potato starch) do not affect the results of the determination of physiologically active compound provided that the analyzed form is obtained at room temperature. The determined content of isoniazid in a solid dosage formulation varies in the range of 286.0 – 296.0 mg and falls within the range recommended by the General Pharmacopoeia Monograph 1.4.2.0009.15 (285 – 315 mg), which indicates that the quality of the drug meets the GMP standards. The linear dependence of the analytical signal on the concentration of physiologically active compound is observed in the range of 161 – 1610 mg for the drug «Isoniazid. Tablets, 300 mg». The calculated detection limits and quantitative determination are 13.5 and 41.0 mg (both in terms of change in the current strength and in the time of titrant generation), respectively. The developed photochemical method for the determination of isoniazid in solid dosed formulation is easy to use, meets the requirements set out in the guidelines for validation of bioanalytical methods, and does not require expensive equipment. The method can be recommended for routine control of the DF quality indicators in any analytical laboratory.

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Assessing Drug-Excipient Interactions in the Formulation of Isoniazid Tablets

Cited by 2 publications

References 9 publications

Design, Synthesis, and Biological Activity of Hydrogen Peroxide Responsive Arylboronate Melatonin Hybrids

Design, Synthesis, and Biological Activity of Hydrogen Peroxide Responsive Arylboronate Melatonin Hybrids

The use of photogenerated iodine for the determination of isoniazid in solid dosage formulation

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