Make and break - Facile synthesis of cocrystals and comprehensive dissolution studies

Batzdorf, Lisa; Zientek, Nicolai; Rump, Doreen; Fischer, Friedrich; Maiwald, Michael; Emmerling, Franziska

doi:10.1016/j.molstruc.2016.11.063

Cited by 14 publications

(9 citation statements)

References 27 publications

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“…This has historically involved use in mineral processing, but is becoming increasingly common in the fine chemicals and pharmaceutical industries [1]. Mechanochemical methods have been used in the synthesis and preparation of a broad range of molecules and materials [2][3][4][5]. Many examples are now available where mechanical treatment has been shown to be a method providing access to novel molecular materials or has been used to enhance the selectivity and the rates of product formation [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…These issues prompted the rapid development of techniques to probe mechanochemical reactions in situ and in real time. To date, this has been performed using X-ray powder diffraction at synchrotron sources, laboratory-based Raman spectroscopy, or a simultaneous combination of the two [3,[15][16][17][18][19]. In situ, real-time monitoring has proven a great advantage to identifying processes and control parameters in mechanochemistry.…”

Section: Introductionmentioning

confidence: 99%

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The effect of ball mass on the mechanochemical transformation of a single-component organic system: anhydrous caffeine

2018

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ABSTARCTMechanochemical methodologies, particularly ball milling, have become commonplace in many laboratories. In the present work, we examine the effects of milling ball mass on the polymorphic conversion of anhydrous caffeine. By investigating a single-phase system, the rate-limiting step of particle-particle contact formation is eliminated. It is found that larger milling balls lead to considerably faster conversion rates. Modelling of the transformation rate suggests that a single, time-independent rate constant is insufficient to describe the transformation. Instead, a convolution of at least two rate-determining processes is required to correctly describe the transformation. This suggests that the early stages of the transformation are governed only by the number of particle-ball collisions. As the reaction proceeds, these collisions less frequently involve reactant, and the rate becomes limited by mass transport, or mixing, even in originally single-phase systems, which become multi-phase as the product is formed. Larger milling balls are less hindered by poorly mixed material. This likely results from a combination of higher impact energies and higher surface areas associated with the larger milling balls. Such insight is important for the selective and targeted design of mechanochemical processes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of ball mass on the mechanochemical transformation of a single-component organic system: anhydrous caffeine

2018

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“…Cocrystals are multicomponent solids that contain two or more neutral molecules, solid at room temperature [ 19 ], in stoichiometric ratio within the same crystal lattice [ 20 ]. They are composed of an API and a cocrystallizing agent (coformer), typically a small organic compound [ 21 ], generally regarded as safe, which may be another drug or a non-toxic molecule [ 20 ]. Cocrystals of poorly aqueous soluble APIs and highly soluble coformers have been shown to impart a solubility advantage that is orders of magnitude higher than the parent drug [ 22 ], as well as a dissolution advantage and increased bioavailability [ 23 ].…”

Section: Pharmaceutical Cocrystalsmentioning

confidence: 99%

Obtaining Cocrystals by Reaction Crystallization Method: Pharmaceutical Applications

et al. 2021

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Cocrystals have gained attention in the pharmaceutical industry due to their ability to improve solubility, stability, in vitro dissolution rate, and bioavailability of poorly soluble drugs. Conceptually, cocrystals are multicomponent solids that contain two or more neutral molecules in stoichiometric amounts within the same crystal lattice. There are several techniques for obtaining cocrystals described in the literature; however, the focus of this article is the Reaction Crystallization Method (RCM). This method is based on the generation of a supersaturated solution with respect to the cocrystal, while this same solution is saturated or unsaturated with respect to the components of the cocrystal individually. The advantages of the RCM compared with other cocrystallization techniques include the ability to form cocrystals without crystallization of individual components, applicability to the development of in situ techniques for the screening of high quality cocrystals, possibility of large-scale production, and lower cost in both time and materials. An increasing number of scientific studies have demonstrated the use of RCM to synthesize cocrystals, mainly for drugs belonging to class II of the Biopharmaceutics Classification System. The promising results obtained by RCM have demonstrated the applicability of the method for obtaining pharmaceutical cocrystals that improve the biopharmaceutical characteristics of drugs.

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“…3,4 In recent years, mechanochemistry has increasingly been applied as a benign synthetic route in a wide range of fields. [5][6][7][8][9][10][11] (e.g., organometallic complexes, [12][13][14] organo-catalysts, 15 cocrystals [16][17][18] , metal-organic frameworks, [19][20][21] alloys, 22 composites, 23 etc. )…”

Section: Introductionmentioning

confidence: 99%

Multi-gram Mechanosynthesis of Salophen-Complex: A Comparative Analysis

Garcı́a¹,

Ong²,

Singh³

et al. 2020

Preprint

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Mechanochemistry is a powerful alternative to traditional solvent-based synthesis as it is environmentally benign, allows for higher yields in shorter reaction times, while minimizing the use of solvents. Although mechanochemical routes are becoming increasingly mainstream in synthetic laboratories, up-scales examples for main group complexes are still rare. Here, motivated by the practical implementation of mechanosynthesis, we demonstrated the synthesis of salen and salophen complexes. The herein reported synthesis displays low E-factor and process mass intensity compared to conventional solution methods. In addition, analyses evaluating environmental parameters, energy consumption and production costs have been performed, showing the multiple advantages mechanochemistry has over convetional solution-based synthesis<br>

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Make and break - Facile synthesis of cocrystals and comprehensive dissolution studies

Cited by 14 publications

References 27 publications

The effect of ball mass on the mechanochemical transformation of a single-component organic system: anhydrous caffeine

The effect of ball mass on the mechanochemical transformation of a single-component organic system: anhydrous caffeine

Obtaining Cocrystals by Reaction Crystallization Method: Pharmaceutical Applications

Multi-gram Mechanosynthesis of Salophen-Complex: A Comparative Analysis

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