Novel Isoniazid cocrystals with aromatic carboxylic acids: Crystal engineering, spectroscopy and thermochemical investigations

Diniz, Luan F.; Souza, Matheus S.; Carvalho, Paulo S.; Silva, Cecília C. P. da; D’Vries, Richard F.; Ellena, Javier

doi:10.1016/j.molstruc.2017.09.115

Cited by 45 publications

(28 citation statements)

References 43 publications

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“…This intense O–H bond signal was derived from the CA absorption peak shift at 3493 and 3275 cm −1 . In addition, the C=O bond of the carboxylic acid in the DAP cocrystal was identified at 1716 and 1691 cm −1 , showing a red shift of the CA absorption peak at 1742 and 1693 cm −1 [ 15 ]. The thermal and water resistance properties were characterized by DSC, TGA, and dynamic vapor sorption.…”

Section: Resultsmentioning

confidence: 99%

Improved Manufacturability and In Vivo Comparative Pharmacokinetics of Dapagliflozin Cocrystals in Beagle Dogs and Human Volunteers

et al. 2021

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Dapagliflozin (DAP), which improves glycemic control in patients with type 2 diabetes mellitus, has poor physical properties against heat and moisture, thus hindering its manufacturing potential. The superior physicochemical properties of a recently developed cocrystal of DAP and citric acid (DAP cocrystal) in comparison with those of DAP and Forxiga®, a patented solvate form with propandiol monohydrate, were identified via structural analysis and moisture sorption isotherm. For the first time, the formulation, manufacturability, and in vivo bioavailability of DAP cocrystals were successfully investigated to develop oral dosage forms that substitute Forxiga®. The intrinsic dissolution rate of DAP cocrystal was controlled by varying particle size distribution. Unlike the direct compression (DC), roller compaction (RC) was more preferable to obtain good flowability of dry granules for a continuous manufacturing system. The cocrystal structure was maintained throughout the stability assessment period. In Vitro dissolution pattern differences of the optimized DAP cocrystal tablet with RC and the reference tablet, Forxiga® 10 mg, were pharmaceutically equivalent within 5% in four different media. Furthermore, comparative pharmacokinetic analysis confirmed that a 10 mg DAP cocrystal tablet with RC was bioequivalent to a 10 mg Forxiga® tablet, as assessed in beagle dogs and human volunteers.

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Section: Resultsmentioning

confidence: 99%

Improved Manufacturability and In Vivo Comparative Pharmacokinetics of Dapagliflozin Cocrystals in Beagle Dogs and Human Volunteers

et al. 2021

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“…The latter, in particular, are more and more commonly pursued as an alternative to salts in the quest for performance enhancement of APIs, because cocrystallization offers greater opportunities than salification: (i) it is viable for molecules that do not display any ionizable moiety; (ii) the possible coformers (i.e., molecules selected to cocrystallize with the API) are more numerous than the possible counterions; (iii) cocrystallization can significantly improve the solubility of the APIs without altering their permeability. As of today, many pharmaceutical cocrystals have been successfully prepared and reported in the literature [ 7 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

et al. 2020

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We report on the preparation, characterization, and bioavailability properties of three new crystal forms of ethionamide, an antitubercular agent used in the treatment of drug-resistant tuberculosis. The new adducts were obtained by combining the active pharmaceutical ingredient with three dicarboxylic acids, namely glutaric, malonic and tartaric acid, in equimolar ratios. Crystal structures were obtained for all three adducts and were compared with two previously reported multicomponent systems of ethionamide with maleic and fumaric acid. The ethionamide-glutaric acid and the ethionamide-malonic acid adducts were thoroughly characterized by means of solid-state NMR (13C and 15N Cross-Polarization Magic Angle Spinning or CPMAS) to confirm the position of the carboxylic proton, and they were found to be a cocrystal and a salt, respectively; they were compared with two previously reported multicomponent systems of ethionamide with maleic and fumaric acid. Ethionamide-tartaric acid was found to be a rare example of kryptoracemic cocrystal. In vitro bioavailability enhancements up to a factor 3 compared to pure ethionamide were assessed for all obtained adducts.

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“…Machado and coworkers mentioned that besides mutations that occur in inhA gene and cause resistance to the isoniazid drug, another genes could suffer from mutations and contribute to isoniazid resistance, like ndh , kasA and oxyR-ahpC from the intergenic region [ 22 , 25 ]. In spite of the low stability and fast degradation when administered with other anti-tuberculosis drugs, [ 26 , 27 , 28 ] isoniazid continues to be an essential drug recommended by WHO to integrate different drug regimens to treat tuberculosis infections [ 23 ]. Some studies made with this drug showed an improvement of the isoniazid solubility by simple dissolution of API in different imidazolium-based ionic liquids, observing that the solubility of the isoniazid decreases with the increase of the alkyl chain in the ionic liquid cation [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Organic Salts Based on Isoniazid Drug: Synthesis, Bioavailability and Cytotoxicity Studies

2020

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Tuberculosis is one of the ten causes of morbidity and mortality worldwide caused by Mycobacterium tuberculosis complex. Some of the anti-tuberculosis drugs used in clinic studies, despite being effective for the treatment of tuberculosis, present serious adverse effects as well as poor bioavailability, stability, and drug-resistance problems. Thus, it is important to develop approaches that could provide shorter drug regimens, preventing drug resistance, toxicity of the antibiotics, and improve their bioavailability. Herein, we reported the use of organic salts based on the isoniazid drug, which can act as an organic cation combined with suitable organic anions such as alkylsulfonate-based (mesylate, R or S-Camphorsulfonate), carboxylate-based (glycolate, vanylate) and sacharinate. The synthesis, characterization, and cytotoxicity studies comparing with the original isoniazid drug have been performed. The possibility to explore dicationic salts seems promising in order to improve original bioavailability, and promote the elimination of polymorphic forms as well as higher stability, which are relevant characteristics that the pharmaceutical industry pursues.

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Novel Isoniazid cocrystals with aromatic carboxylic acids: Crystal engineering, spectroscopy and thermochemical investigations

Cited by 45 publications

References 43 publications

Improved Manufacturability and In Vivo Comparative Pharmacokinetics of Dapagliflozin Cocrystals in Beagle Dogs and Human Volunteers

Improved Manufacturability and In Vivo Comparative Pharmacokinetics of Dapagliflozin Cocrystals in Beagle Dogs and Human Volunteers

Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

Organic Salts Based on Isoniazid Drug: Synthesis, Bioavailability and Cytotoxicity Studies

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