Mechanistic Understanding of Competitive Destabilization of Carbamazepine Cocrystals under Solvent Free Conditions

Alsirawan, Mhd. Bashir; Lai, Xiaojun; Prohens, Rafel; Vangala, Venu R.; Shelley, Petroc; Bannan, Thomas J.; Topping, David; Paradkar, Anant

doi:10.1021/acs.cgd.0c00735

Cited by 9 publications

(18 citation statements)

References 17 publications

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“…In order to understand experimental observations, energy calculations were conducted and correlated with that of experimental results. As previously reported, the destabilization reaction involves reaching an equilibrium phase either as vapor or eutectic phase as in the case of previously reported CZ/NT destabilization . This is followed by the formation of the thermodynamic preferred cocrystal (eq ).…”

supporting

confidence: 56%

“…Additionally, the produced vapor pressure is at a supersaturation state with respect to the CA/ OX cocrystal, leading to its nucleation and crystal growth. Compared to previously reported CZ/NT and CZ/SA systems, 9…”

Section: T H Imentioning

confidence: 82%

“…As previously reported, the destabilization reaction involves reaching an equilibrium phase either as vapor or eutectic phase as in the case of previously reported CZ/NT destabilization. 9 This is followed by the formation of the thermodynamic preferred cocrystal (eq 1).…”

Section: T H Imentioning

confidence: 99%

“…The competitive destabilization pathway of two carbamazepine cocrystals at solvent -free conditions was found to vary depending on the sublimation/melting behavior of the components as well as on the processing conditions. 9 Carbamazepine/nicotinamide 1:1 cocrystal (CZ/NT) can destabilize in the presence of saccharin (SA) at relatively high temperatures via a eutectic phase resulting in the formation of a carbamazepine/saccharin 1:1 cocrystal (CZ/ SA). On the other hand, the presence of NT with CZ/SA during neat grinding or at lower temperatures causes the destabilization of CZ/SA via vapor phase and results in the formation of CZ/NT.…”

mentioning

confidence: 99%

“…Schematic representation of eutectic or vapor phase mediated competitive destabilization of CA (left) and CZ (right) cocrystals.…”

mentioning

confidence: 99%

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Solid-State Competitive Destabilization of Caffeine Malonic Acid Cocrystal: Mechanistic and Kinetic Investigations

Alsirawan

Lai

Prohens

et al. 2020

Crystal Growth & Design

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The main objective of this research is to investigate both the mechanism and the kinetics of solvent-free destabilization of the model caffeine/malonic acid cocrystal (CA/MO 2:1) in the presence of oxalic acid (OX) as a structural competitor to malonic acid (MO). Competitive destabilization of CA/MO and subsequent formation of caffeine/oxalic acid (CA/OX) take place at temperatures significantly below their melting points. The destabilization mechanism was found to be mediated by sublimation of both CA/MO and OX. During CA/MO destabilization, free CA could not be detected, and direct transformation to the CA/OX cocrystal was observed. The destabilization kinetics follow Prout–Tompkins nucleation and the crystal growth model with an activation energy of 133.91 kJ/mol, and subsequent CA/OX growth kinetics follow Ginstling–Brounshtien and three-dimensional diffusion models with an activation energy range of 130.45–132.57 kJ/mol.

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supporting

confidence: 56%

Section: T H Imentioning

confidence: 82%

Section: T H Imentioning

confidence: 99%

mentioning

confidence: 99%

“…Schematic representation of eutectic or vapor phase mediated competitive destabilization of CA (left) and CZ (right) cocrystals.…”

mentioning

confidence: 99%

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Solid-State Competitive Destabilization of Caffeine Malonic Acid Cocrystal: Mechanistic and Kinetic Investigations

Alsirawan

Lai

Prohens

et al. 2020

Crystal Growth & Design

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A New Look at the Mechanism of Cocrystal Formation and Coformers Exchange in Processes Forced by Mechanical and/or Thermal Stimuli –ex situandin situStudies of Low‐Melting Eutectic Mixtures

Dudek,

Trzeciak,

Tajber

et al. 2024

Chemistry A European J

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Three different devices: ball‐mill, hot stage melting, and magic angle spinning (MAS) NMR rotor were used for the preparation of ethenzamide (ET) cocrystals with glutaric acid (GLU), ethylmalonic acid (EMA) and maleic acid (MAL) as coformers. The common features of the solvent‐free methods of cocrystal formation (grinding, melting) are presented on the basis of arguments obtained by solid state NMR spectroscopy. Thermal analysis proved that the eutectic phase arises over a wide range of molar ratios of components for each binary system. Experimental and theoretical methods allowed to provide details about the pathway of the reaction mechanism. It was found that the formation of ET cocrystals is a complex process that requires five steps. Variable temperature 1D and 2D MAS NMR experiments allowed to track physico‐chemical processes taking place in a molten state. Moreover, it was found that in a multicomponent mixture consisting of ET, EMA, GLU, and MAL, ET in the molten phase behaves as a specific selector choosing only one partner to form binary cocrystals according to energy preferences. The stabilization energies (Estab) and molecular electrostatic potential (MEP) maps computed for the cocrystals and their individual components rationalize the selection rules and explain the relationships between individual species.

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Mechanochemical Transformations of Pharmaceutical Cocrystals: Polymorphs and Coformer Exchange

Trzeciak,

Dudek,

Potrzebowski

2024

Chemistry A European J

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Transformations of solid samples under solvent‐free or minimal solvent conditions set the future trend and define a modern strategy for the production of new materials. Of the various technologies tested in recent years, the mechanochemical approach seems to be the most promising. The aim of this review article is to present the current state of art in solid state research on binary systems, which have found numerous applications in the pharmaceutical and materials science industries. This article is divided into three sections. In the first part, we describe the new equipment improvements. A brief description of techniques dedicated to ex‐situ and in‐situ studies of progress and the mechanism of solid matter transformation is presented. In the second section, we discuss the problem of cocrystal polymorphism highlighting the issue related with correlation between mechanochemical parameters (time, temperature, energy, molar ratio, liquid assistant, surface energy, crystal size, crystal shape) and preference for the formation of requested polymorph. The last part is devoted to the description of the processes of coformer exchange in binary systems forced by mechanical and/or thermal stimuli. The influence of the thermodynamic factor on the selection of the best‐suited partner for the formation of a two‐component structure is presented.

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Mechanistic Understanding of Competitive Destabilization of Carbamazepine Cocrystals under Solvent Free Conditions

Cited by 9 publications

References 17 publications

Solid-State Competitive Destabilization of Caffeine Malonic Acid Cocrystal: Mechanistic and Kinetic Investigations

Solid-State Competitive Destabilization of Caffeine Malonic Acid Cocrystal: Mechanistic and Kinetic Investigations

A New Look at the Mechanism of Cocrystal Formation and Coformers Exchange in Processes Forced by Mechanical and/or Thermal Stimuli –ex situandin situStudies of Low‐Melting Eutectic Mixtures

Mechanochemical Transformations of Pharmaceutical Cocrystals: Polymorphs and Coformer Exchange

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