Crystal engineering: co-crystals of cinnamic acid derivatives with a pyridyl derivative co-crystallizer

Lorenzo, Daniel A.; Forrest, Sebastian J. K.; Sparkes, Hazel A.

doi:10.1107/s2052520615019678

Cited by 8 publications

(3 citation statements)

References 30 publications

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“…TCA (9) has been used as a cocrystal former with several amides (Nisar et al, 2018) and is considered a GRAS agent. The presence of C O and O-H groups act as promoting synthons for hydrogen bonding during cocrystallization (Lorenzo et al, 2016;Eedara et al, 2019). TCA was also found to be noncytotoxic against the BJ cell line in our present study.…”

Section: Selection Of Coformersupporting

confidence: 75%

New cocrystals of heterocyclic drugs: structural, antileishmanial, larvicidal and urease inhibition studies

Murtaza

Khan

Farooq

et al. 2023

Acta Crystallogr C Struct Chem

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Many heterocycles have been developed as drugs due to their capacity to interact productively with biological systems. The present study aimed to synthesize cocrystals of the heterocyclic antitubercular agent pyrazinamide (PYZ, 1, BCS III) and the commercially available anticonvulsant drug carbamazepine (CBZ, 2, BCS class II) to study the effect of cocrystallization on the stability and biological activities of these drugs. Two new cocrystals, namely, pyrazinamide–homophthalic acid (1/1) (PYZ:HMA, 3) and carbamazepine–5-chlorosalicylic acid (1/1) (CBZ:5-SA, 4), were synthesized. The single-crystal X-ray diffraction-based structure of carbamazepine–trans-cinnamic acid (1/1) (CBZ:TCA, 5) was also studied for the first time, along with the known cocrystal carbamazepine–nicotinamide (1/1) (CBZ:NA, 6). From a combination drug perspective, these are interesting pharmaceutical cocrystals to overcome the known side effects of PYZ (1) therapy, and the poor biopharmaceutical properties of CBZ (2). The purity and homogeneity of all the synthesized cocrystals were confirmed by single-crystal X-ray diffraction, powder X-ray diffraction and FT–IR analysis, followed by thermal stability studies based on differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Detailed intermolecular interactions and the role of hydrogen bonding towards crystal stability were evaluated quantitatively via Hirshfeld surface analysis. The solubility of CBZ at pH 6.8 and 7.4 in 0.1 N HCl and H2O were compared with the values of cocrystal CBZ:5-SA (4). The solubility of CBZ:5-SA was found to be significantly improved at pH 6.8 and 7.4 in H2O. All the synthesized cocrystals 3–6 exhibited a potent urease inhibition (IC50 values range from 17.32 ± 0.89 to 12.3 ± 0.8 µM), several times more potent than standard acetohydroxamic acid (IC50 = 20.34 ± 0.43 µM). PYZ:HMA (3) also exhibited potent larvicidal activity against Aedes aegypti. Among the synthesized cocrystals, PYZ:HMA (3) and CBZ:TCA (5) were found to possess antileishmanial activity against the miltefosine-induced resistant strain of Leishmania major, with IC50 values of 111.98 ± 0.99 and 111.90 ± 1.44 µM, respectively, in comparison with miltefosine (IC50 = 169.55 ± 0.20 µM).

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Section: Selection Of Coformersupporting

confidence: 75%

New cocrystals of heterocyclic drugs: structural, antileishmanial, larvicidal and urease inhibition studies

Murtaza

Khan

Farooq

et al. 2023

Acta Crystallogr C Struct Chem

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“…It is thus not surprising that poor biopharmaceutical properties are the main reason that <1% of active compounds eventually make it into marketplace. [32][33][34] …”

Section: Problems Encountered During the Development Of Apimentioning

confidence: 99%

Untitled

Payghan¹

2017

AJP

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The objective of this study was to investigate whether the miscibility of a drug and coformer, as predicted by Hansen solubility parameters (HSPs), can indicate cocrystal formulation. It was also our aim to evaluate various HSPs-based approaches in miscibility predication. It is concerned with some new aspects of solvent properties, and these properties can help predict solvent behavior during the manufacturing processes and will be useful in predicting behavior in many other fields of endeavor. The work on the solubility parameter, in particular, deals with fundamental attractions among materials and should have broad application. To say that hydrogen bonding had no significant effect on solvent retention without defining hydrogen bonding was not satisfactory. To better define hydrogen bonding and polar bonding, a study based on the solubility parameter was initiated. This eventually led to the concept of a three-dimensional (3D) solubility parameter (E). The 3D solubility parameter is has been assumed that ∆E is given by the simple sum of the energies arising from dispersion forces, ∆E d , polar forces, ∆E P , and hydrogen bonding forces, ∆E h. Group contribution method for the estimation of Hansen solubility parameters of pure organic compounds is presented by characteristic groups ensure the prediction of HSP for a broad series of organic compounds, including those having complex multiring, heterocyclic, and aromatic structures. The predictions are exclusively based on the molecular structure of compounds, and no experimental data are needed. Solubility parameters for solutes are obtained by group contribution method. Using Fedor's substituent constants, Hoy's molar attraction constants and Van Kreevalen constants were calculated and are currently used methods. The resultant Δ values of active pharmaceutical ingredient and coformers are compared, and their solid-state miscibility is expressed. Possibility of cocrystal formulation by Krevlens is Δδ < 5MP and Greenhalgh Δδ < 7MP can be predicted.

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“…[ [43][44][45] The angle of repose should be in between 25 and 300 for good flow properties of crystals. The bulk density of a crystal depends primarily on particle size distribution, particle shape and the tendency of particle to adhere together.…”

Section: Spray Dryingmentioning

confidence: 99%

Untitled

Payghan¹

2017

AJP

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Aim: Hansen solubility parameters (HSPs) have been used to predict the miscibility of a drug with excipients/ carriers in solid dispersions. This study investigated whether the miscibility of a drug and its coformer components, as predicted by theoretical miscibility tools, this eventually led to the concept of a three dimensional solubility parameter (E). This is to determine whether the process parameters of the laboratory-scale spray dryer affects the solubility behavior and physical stability of the solid dispersion. Group-contribution method for the estimation of HSPs of pure organic compounds is presented by characteristic groups ensures the prediction of HSP for a broad series of organic compounds including those having complex multi-ring, heterocyclic, and aromatic structures. The predictions are exclusively based on the molecular structure of compounds, and no experimental data are needed. , theoretical screening and comparison of orlistat by 3D parameter, formulation of spray dried cocrystals, optimization of spray drying process parameters. Result and Discussion: The selected coformer was based on HSP by which three methods are used such as Fedor's methods, van Krevelen's methods, and hoys methods. Based on their given value the selection of coformer was done by Krevelen's ∆δ≤5MP and Greenhalgh ∆δ≤7MP. Proposed structure of orlistat was developed using ChemSketch software. The thorough understanding of the structure of API and coformer is required to locate correctly the hydrogen bonding. Coformer selection was done based on hydrogen bonding in structure. The surface morphology studies revealed that the solid dispersion was closely compacted into small spherical form. Conclusion: Considerable improvement in the dissolution rate of orlistat from optimized formulation was due to an increased solubility that is attributed to the supersaturation from the fine cocrystals is faster due to the large specific surface area of small particles and prevention of phase transformation to pure orlistat.

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Crystal engineering: co-crystals of cinnamic acid derivatives with a pyridyl derivative co-crystallizer

Cited by 8 publications

References 30 publications

New cocrystals of heterocyclic drugs: structural, antileishmanial, larvicidal and urease inhibition studies

New cocrystals of heterocyclic drugs: structural, antileishmanial, larvicidal and urease inhibition studies

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