Preparation of Pyrazinamide Eutectics versus Cocrystals Based on Supramolecular Synthon Variations

Rajbongshi, Trishna; Sarmah, Kashyap Kumar; Sarkar, Ankita; Ganduri, Ramesh; Cherukuvada, Suryanarayan; Thakur, Tejender S.; Thakuria, Ranjit

doi:10.1021/acs.cgd.8b00878

Cited by 26 publications

(23 citation statements)

References 51 publications

(75 reference statements)

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“…Several polymorphs of cocrystals of PZA with succinic acid (Cherukuvada and Nangia, 2012;Luo and Sun, 2013), malonic acid (Kulla et al, 2017) and theophylline (Eddleston et al, 2015) have been found and investigated. Different binary mixtures leading to either cocrystals or eutectic systems have been described by Rajbongshi et al (Rajbongshi et al, 2018). A ternary cocrystal has been designed by using a "drug-bridge-drug" strategy involving PZA combined with another first-line antitubercular drug isoniazid using fumaric acid as the bridge (Liu et al, 2018).…”

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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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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“…If the adhesive interactions dominating the resulting compound are characterized as a cocrystal, and yet if both interactions, adhesive and cohesive, are balanced and a match of size/shape between the components occurs, a solid solution is formed [39]. Furthermore, Rajbongshi et al also studied the formation of eutectics through crystallization processes with pyrazinamide and different aromatic carboxylic acids characterized by a "V" shape phase diagram [40].…”

Section: Thedes For Tuberculosis Treatmentmentioning

confidence: 99%

Therapeutic Deep Eutectic Systems towards the Treatment of Tuberculosis and Colorectal Cancer: Opportunities and Challenges

2021

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What if a new technology based on therapeutic deep eutectic systems would disrupt the current treatment of major economic and socially burden diseases? The classical definition of eutectic systems is that they are the combination of two or more compounds that interact via hydrogen bonds, from which results a melting temperature depression in comparison with that of its individual components. Therapeutic deep eutectic systems are defined as eutectic systems in which at least one of the individual components is an active pharmaceutical ingredient, or a eutectic system in which the active pharmaceutical ingredient is dissolved. Current literature reports on tuberculosis have been mostly based on the most common anti-tuberculosis drugs prescribed. Using eutectic systems based on naturally occurring molecules known for their anti-microbial activity may also present a promising therapeutic strategy able to cope with the prevalence of Mycobacterium tuberculosis and prevent the appearance of multidrug resistance strains. With regards to colorectal cancer, literature has been unravelling combinations of terpenes with anti-inflammatory drugs that are selectively cytotoxic towards colorectal cancer cells and do not compromise the viability of normal intestinal cells. This technology could contribute to preventing tumor growth and metastasis while providing a patient compliance therapeutics, which will be crucial to the success of overcoming the challenges presented by cancers.

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“…In order to understand the formation of eutectics as opposed to cocrystals for selected combinations, we have performed supramolecular synthon energy calculations similar to our previous work. [5] Specifically, we extracted clusters of molecules from the published structures of ETZ-FRA and ETZ-SA cocrystals (Figure 8) and computed the intermolecular interaction energy using DFT. Subsequently, hypothetical clusters corresponding to ETZ-CA and ETZ-BA adducts were generated by replacing the hydroxyl group with hydrogen atoms in FRA and SA molecules, respectively.…”

Section: Supramolecular Synthon Energy Calculationsmentioning

confidence: 99%

Mechanosynthesis of Eutectics of Anti‐Inflammatory Drug Ethenzamide – A Comparison with Analogous Cocrystals

Rajbongshi

Sarmah²,

Ganduri

et al. 2021

Chemistry Methods

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Mechanochemical milling of ethenzamide (ETZ), a nonsteroidal anti-inflammatory drug, with substituted aromatic carboxylic acids as well as anti-tuberculosis drug pyrazinamide (PZA) resulted in the formation of eutectics. Although a large number of cocrystals as well as polymorphic cocrystals are reported for ETZ, for the first time we have synthesized six eutectics including an instance of a drug-drug eutectic system. Supramolecular synthon energy calculations validate the formation of eutectic mixtures over cocrystals with coformers considered in our study.

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Preparation of Pyrazinamide Eutectics versus Cocrystals Based on Supramolecular Synthon Variations

Cited by 26 publications

References 51 publications

The phase relationship between the pyrazinamide polymorphs α and γ

The phase relationship between the pyrazinamide polymorphs α and γ

Therapeutic Deep Eutectic Systems towards the Treatment of Tuberculosis and Colorectal Cancer: Opportunities and Challenges

Mechanosynthesis of Eutectics of Anti‐Inflammatory Drug Ethenzamide – A Comparison with Analogous Cocrystals

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