Crystal Engineering of the Composition of Pharmaceutical Phases:  Multiple-Component Crystalline Solids Involving Carbamazepine

Fleischman, S.; Kuduva, Srinivasan S.; McMahon, Jennifer A.; Moulton, Brian; Walsh, Rosa D. Bailey; Rodrı́guez-Hornedo, Naı́r; Zaworotko, Michael J.

doi:10.1021/cg034035x

Cited by 510 publications

(454 citation statements)

References 60 publications

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“…Acetone gels of 2 containing 50 mg of CBZ after two weeks formed a large single crystal characterised as the triclicinic acetone solvate. [39][40] Parallel experiments in pure acetone did not produce any crystals. In this case, the gel induces crystallisation at lower saturation than the level required for a pure solvent crystallisation.…”

Section: Crystallization Of Cbz From Other Gelsmentioning

confidence: 96%

Anion-switchable supramolecular gels for controlling pharmaceutical crystal growth

et al. 2010

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The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. Gel media have been utilized for over a century for the growth of inorganic, organic and protein crystals. [1][2][3][4][5] The improved physical characteristics of the resulting crystals (better optical quality, larger size and fewer defects) are usually ascribed to the suppression of convection currents, sedimentation and nucleation afforded by the viscous gel environment. [6][7] In many instances the gel is thought to act as an inert matrix within which crystal growth occurs, however in some cases, the gel structure has been shown to influence the polymorphism, enantiomorphism and habit of crystals. 2 Occasionally gel fibres may become incorporated into the crystal, giving rise to composite materials. 8Conventional gels are formed using polymeric or clay-like materials such as gelatine, solubility were investigated to demonstrate their potential to act as crystallisation media for molecular organic compounds. Compounds 2, and 4 have been reported previously. [23][24] Novel compounds 1 and 3 were prepared by standard methods as detailed in the supplementary information. Gelators 1 -3 were chosen because they reliably form gels in a number of solvents ranging from aqueous systems to toluene. The fibrous nature of the gels is evidenced by SEM images of the dried xerogels ( Figure 1a,b). Compound 4 is a metallogelator which forms blue coloured gels with substoichiometric amounts of CuCl 2 in methanol:water. 23 Between them, these gelators can gel a range of solvents, at different temperatures (T gel ), and with a different critical gelator concentration (CGC). This class of compound has the potential to form the basis of a library of gelators which will allow the selection of gel properties and specific functionalities to match the compound and crystallisation conditions of interest. The synthetic versatility of these gelators could also in principle allow the incorporation of tailored heteronucleating functionality. While we focus upon bis(urea) compounds, the concepts outlined herein equally apply to any LMWG.Crystallisation experiments were undertaken using a range of organic compounds of both drug and non-drug species in parallel in both gel and solution media. We undertook an initial screen using candidate compounds 2-hydroxy benzyl alcohol (HBA, 5), Aspirin (ASP, 6), carbamazepine (CBZ, 7), 1-(3-methylsulfanyl-phenyl)-3-pyridin-2-yl-urea (SPU, 8) and 1,3-bis(m-nitrophenyl)urea (NPU, 9). We then carried out a detailed study on CBZwith all gelators, and a follow up study on gelator ...

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Section: Crystallization Of Cbz From Other Gelsmentioning

confidence: 96%

Anion-switchable supramolecular gels for controlling pharmaceutical crystal growth

et al. 2010

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“…However, there is significant different between patterns produced using non-stoichiometric and stoichiometric methods. Solvent evaporation method yields more sharp and prominent peaks due to crystalline nature of the co-crystal produced no agitation and stirring effect involve during the crystallization process [18]. Table I shows the summary of the overall analysis results including the co-crystals formed from acetonitrile, ethyl acetate, formic acid, ethanol and propanol.…”

Section: A Powder X-ray Diffraction (Pxrd)mentioning

confidence: 99%

“…Moreover, CBZ has four different anhydrous polymorph forms and dehydrate forms, and CBZ form III is known as the mainly stable anhydrous form at ambient conditions [17]. Previous study has reported that co-crystals have been successfully formed using slow evaporation, reaction co-crystallisation, solid state grinding and slurry [18]- [23].…”

Section: Introductionmentioning

confidence: 99%

Carbamazepine-Fumaric Acid and Carbamazepine-Succinic Acid Co-crystal Screening Using Solution Based Method

Rahman¹,

Rahim²,

Chou³

et al. 2017

IJCEA

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Abstract-Co-crystal plays a critical role in the pharmaceutical industry and becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ) and co-crystal former (CCF) of fumaric acid (FUM) and succinic acid (SA) using non-stoichiometric method (addition of CBZ to CCF saturated solution) and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF) in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FT-IR). The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method for CBZ-FUM system and in all methods for CBZ-SA system. The findings from this analysis revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvents systems. DSC analysis had shown that the melting point of CBZ-FUM and CBZ-SA co-crystals were in the range similar to the previous study. The characterization using FT-IR indicated that the functional groups which include amides and carboxylic acids were presented in the co-crystal produced. Further study on the co-crystal solubility and dissolution rate is needed in order to access the efficacy of the co-crystal since the screening methods have been successfully confirmed the formation of the co-crystal.

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“…[1][2][3][4][5][6][7][8][9][10] The number of potential co-crystal formers (CCFs) can reach up to several hundred; therefore, an efficient strategy for CCF screening in drug discovery and development is required. High throughput screening (HTS) technologies have been employed for CCF screening.…”

mentioning

confidence: 99%

Stability Order of Caffeine Co-crystals Determined by Co-crystal Former Exchange Reaction and Its Application for the Validation of in Silico Models

2015

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The purpose of the present study was to determine the thermodynamic stability orders of co-crystals by co-crystal former (CCF) exchange reactions. Caffeine (CA) was employed as a model drug. The CCF exchange reaction was performed by liquid-assisted grinding using ethanol. When oxalic acid (OX) was added to CA-citric acid co-crystal (CA-CI), CA-CI converted to CA-OX, suggesting that CA-OX is more stable than CA-CI. The stability orders of other co-crystals were determined in the same manner. The stability order of CA co-crystals was determined as CA-OX≈CA-p-hydroxybenzoic acid (HY)>CA-CI>CA-malonic acid>CA-maleic acid. The stability order correlated with the difference in hydrogen bond energy estimated in silico, except for CA-HY. The π-π stacking in CA-HY was suggested as a reason for this discrepancy. The CCF exchange reaction was demonstrated as a useful method to determine the stability order of co-crystals, which can be used for the validation of in silico parameters to predict co-crystal formation.Key words co-crystal; co-crystal former; exchange reaction; caffeine; hydrogen bond energy Co-crystals have recently received much attention as a means of improving physicochemical properties of active pharmaceutical ingredients.1-10) The number of potential co-crystal formers (CCFs) can reach up to several hundred; therefore, an efficient strategy for CCF screening in drug discovery and development is required. High throughput screening (HTS) technologies have been employed for CCF screening.10-15) However, CCF selection by HTS remains a time-and resource-consuming task. Therefore, an effective pre-screening method for CCF selection would be valuable for drug discovery and development. In the case of salt selection, the difference in pK a values between a drug and a counterion (ΔpK a ) has been used as a criterion for the selection of potential counter-ion candidates.16) Similarly, some in silico physicochemical parameters for CCF selection were proposed by several research groups. [17][18][19][20] For example, the difference in hydrogen bond energy between a co-crystal and each of the sole components (ΔE) was proposed by Musumeci et al., based on the hypothesis that the formation of a co-crystal becomes more probable as ΔE becomes larger.21-23) However, ΔE has not been rigorously validated due to the lack of information about the stability order of co-crystals. The stability order of co-crystals can be determined by CCF exchange reactions. In the literature, there were a few studies on the CCF exchange reactions (a sulfonamide derivative 24) and carbamazepine 25) ). However, in these studies, only a few CCFs were employed so that the data is insufficient for validating in silico models.The purpose of the present study was to determine the stability orders of co-crystals by CCF exchange reaction. Caffeine (CA) was employed as a model drug. The stability order of five CA co-crystals was determined using the CCF exchange reaction. The stability order was then compared with the ΔE estimated in silico.

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Crystal Engineering of the Composition of Pharmaceutical Phases: Multiple-Component Crystalline Solids Involving Carbamazepine

Cited by 510 publications

References 60 publications

Anion-switchable supramolecular gels for controlling pharmaceutical crystal growth

Anion-switchable supramolecular gels for controlling pharmaceutical crystal growth

Carbamazepine-Fumaric Acid and Carbamazepine-Succinic Acid Co-crystal Screening Using Solution Based Method

Stability Order of Caffeine Co-crystals Determined by Co-crystal Former Exchange Reaction and Its Application for the Validation of in Silico Models

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