Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble carriers: phase equilibria, solid-state characterisation and in-vivo/pharmacodynamic evaluation

Abdelkader, Hamdy; Abdallah, Ossama Y.; Salem, Hesham; Alani, Adam W.G.; Alany, Raid G.

doi:10.1111/jphp.12277

Cited by 15 publications

(6 citation statements)

References 23 publications

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“…A molar ratio binary phase diagram (Figure S5, Supplementary Materials) was constructed in order to estimate if the miscibility and interaction propensity between ENT and THP anhydrous is high enough to generate a thermodynamically stable cocrystal [66]. Two distinct melting points, close to the characteristic melting points of the starting compounds, were observed in all ratios, and thus the two well-separated solidus-liquidus curves of the phase diagram could not predict the formation of a cocrystal or a eutectic mixture and evidence any solid-state interaction [67]. Thermal analysis displayed intact THP anhydrous crystals that did not dissolve into the molten phase of ENT, until they gradually melted near the melting point of THP.…”

Section: Cocrystal Screening Methodsmentioning

confidence: 99%

Structural and Energetic Aspects of Entacapone-Theophylline-Water Cocrystal

Karagianni

Quodbach

Weingart

et al. 2022

Solids

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Pharmaceutical cocrystals are currently gaining interest among the scientific community, due to their great potential for providing novel crystalline forms with superior properties such as solubility, dissolution rate, bioavailability, and stability. Robust computational tools are valuable tools in the rationalization of cocrystal formation, by providing insight into the intermolecular interactions of multicomponent molecular solids. In this study, various computational techniques based on charge density analysis were implemented to assess structural and energetical perspectives of the interactions responsible for the formation and stability of entacapone-theophylline-water (ETP-THP-water, 1:1:1). Significant non-covalent interactions (NCIs) were identified and evaluated by Hirshfeld surface analysis and density functional theory (DFT) computations, and three-dimensional networks (energy vector diagrams, lattice energy frameworks) were constructed, outlining the crucial stabilizing role of water and the dominance of π-π stacking interactions in the cocrystal. Furthermore, thermal dehydration studies confirmed the strong binding of water molecules in the crystal lattice, as expressed by the high activation energy.

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Section: Cocrystal Screening Methodsmentioning

confidence: 99%

Structural and Energetic Aspects of Entacapone-Theophylline-Water Cocrystal

Karagianni

Quodbach

Weingart

et al. 2022

Solids

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“…Low-molecular-weight excipients, such as urea and sugars, have also been extensively investigated. However, their solubilizing capacity is limited due to both their chemical neutrality and their lack of sufficient binding sites and ionizable groups [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen

et al. 2023

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Since its introduction to the market in the 1970s, ketoprofen has been widely used due to its high efficacy in moderate pain management. However, its poor solubility and ulcer side effects have diminished its popularity. This study prepared forms of ketoprofen modified with three basic excipients: tris, L-lysine, and L-arginine, and investigated their ability to improve water solubility and reduce ulcerogenic potential. The complexation/salt formation of ketoprofen and the basic excipients was prepared using physical mixing and coprecipitation methods. The prepared mixtures were studied for solubility, docking, dissolution, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), in vivo evaluation for efficacy (the writhing test), and safety (ulcerogenic liability). Phase solubility diagrams were constructed, and a linear solubility (AL type) curve was obtained with tris. Docking studies suggested a possible salt formation with L-arginine using Hirshfeld surface analysis. The order of enhancement of solubility and dissolution rates was as follows: L-arginine > L-lysine > tris. In vivo analgesic evaluation indicated a significant enhancement of the onset of action of analgesic activities for the three basic excipients. However, safety and gastric protection indicated that both ketoprofen arginine and ketoprofen lysine salts were more favorable than ketoprofen tris.

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“…Adverse reactions such as nausea, vomiting, diarrhea and elevated serum liver enzymes have been reported for nimesulide [20]. Many attempts to improve the solubility and dissolution rate of nimesulide have been reported in the literature, including: eutectic formation with nicotinamide [21], solid dispersions with PEG and PVP [22,23], complexation with cyclodextrins [24]. [13,14] and is a potential drug for future treatment strategies against the SARS-CoV-2 virus, as it appears to completely eliminate, indirectly, the B0AT1 protein transport function [15].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…DSC is a very precise and accessible technique to determine the formation of cocrystals or eutectics. Many researchers have used this technique to determine the formation of eutectics and cocrystals between nimesulide and various coformers such as: nicotinamide [21], PVP [22], PEG [22,23], urea [23] and pyridine analogues [30]. To the best of our knowledge, only DSC data of pure nimesulide and, respectively, salicylic acid are found in the literature [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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Thermal Behavior of the Nimesulide-Salicylic Acid Eutectic Mixtures Prepared by Mechanosynthesis and Recrystallization

et al. 2021

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Nimesulide, salicylic acid and their binary mixtures were studied by differential scanning calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The study of such systems is a promising and viable approach for solving the problem of poor solubility of materials in general and drug systems in particular. All areas of human activity are inextricably linked to materials, and thus, the study presented in the paper and not reported in the literature is very important and provides useful data for those working in various fields. The eutectic mixtures were obtained by mechanosynthesis and by recrystallization from ethanol over the entire 0–1 range of molar fractions. For both situations at the molar fraction of nimesulide 0.5, the mixture has a eutectic that suggests an increase in solubility at this composition. The interactions that take place between the components were determined with the help of the excess thermodynamic functions (GE, SE, µE), which highlight the deviation from the ideality of the considered binary systems.

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Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble carriers: phase equilibria, solid-state characterisation and in-vivo/pharmacodynamic evaluation

Abstract: The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug.

Cited by 15 publications

References 23 publications

Structural and Energetic Aspects of Entacapone-Theophylline-Water Cocrystal

Structural and Energetic Aspects of Entacapone-Theophylline-Water Cocrystal

Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen

Thermal Behavior of the Nimesulide-Salicylic Acid Eutectic Mixtures Prepared by Mechanosynthesis and Recrystallization

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