Polymorphism of Carbamazepine Pharmaceutical Cocrystal: Structural Analysis and Solubility Performance

Surov, Artem O.; Drozd, Ksenia V.; Ramazanova, Anna G.; Churakov, Andrei V.; Vologzhanina, Anna V.; Kulikova, Elizaveta S.; Perlovich, German L.

doi:10.3390/pharmaceutics15061747

Cited by 8 publications

(4 citation statements)

References 83 publications

(117 reference statements)

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“…Beyond the fact that cocrystals are solid forms different from the solid reactants they originate, literature also lately reported several examples of polymorphic cocrystals − and solvate cocrystals. − These are mostly produced by conventional methods. Though the potentiality of scCO 2 -based techniques to control polymorphism has been addressed for homocrystals, − only few articles reported polymorphism of cocrystals, , one for the production of a solvate, and none has ever reported the obtention of a cocrystal solvate.…”

Section: Introductionmentioning

confidence: 99%

Unraveling a Unique Metastable Phase of a Proxyphylline Cocrystal Exclusively Produced by Compressed Carbon Dioxide

Ercicek,

Marchivie,

Nimod

et al. 2024

Crystal Growth & Design

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In this work, racemic proxyphylline ((±)-PXL, a chiral drug) was cocrystallized for the first time with 4-hydroxybenzoic acid (4-HBA) from three solvents (acetone, ethyl acetate, and isobutanol) and using CO2 as an antisolvent. The obtained solid forms were compared to those produced by liquid-assisted grinding (LAG). It is shown that though both methods produce a racemic compound (±)-PXL1:4-HBA1 cocrystal, LAG promotes the crystallization of an orthorhombic Pna21 form (Phase I), whereas CO2-assisted crystallization gives rise to an original monoclinic C2/c form with partial inclusion of CO2 and water molecules (Phase II). The structure of Phase II originates from this inclusion since this phase is never obtained in the absence of CO2. Concomitant cocrystallization of Phase I and Phase II occurs during CO2-assisted crystallization in proportions that vary with solvents and temperature. Our study shows that Phase II transforms progressively into Phase I upon storage or heating.

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Section: Introductionmentioning

confidence: 99%

Unraveling a Unique Metastable Phase of a Proxyphylline Cocrystal Exclusively Produced by Compressed Carbon Dioxide

Ercicek,

Marchivie,

Nimod

et al. 2024

Crystal Growth & Design

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“…CBZ is an anticonvulsant drug that has been widely used in clinics for more than 50 years to treat epilepsy, trigeminal neuralgia, and bipolar disorder . CBZ is a commonly used API for cocrystallization with highly soluble coformers − due to its low water solubility and irregular gastrointestinal absorption . To date, over 60 crystal structures of the CBZ multicomponent crystals, including cocrystals, salts, and their hydrates/solvates/polymorphs, have been deposited in the Cambridge Structural Database (CSD), and the number continues to expand annually. ,− Despite the variety of crystal structures, no ternary cocrystals of CBZ have been obtained.…”

Section: Introductionmentioning

confidence: 99%

“…CBZ is a commonly used API for cocrystallization with highly soluble coformers − due to its low water solubility and irregular gastrointestinal absorption . To date, over 60 crystal structures of the CBZ multicomponent crystals, including cocrystals, salts, and their hydrates/solvates/polymorphs, have been deposited in the Cambridge Structural Database (CSD), and the number continues to expand annually. ,− Despite the variety of crystal structures, no ternary cocrystals of CBZ have been obtained. Meanwhile, such an attempt has already been made, resulting in a new polymorph of the CBZ binary cocrystal with 4-hydroxybenzoic acid …”

Section: Introductionmentioning

confidence: 99%

Rational Design of the Carbamazepine Ternary Cocrystals

Boycov,

Drozd,

Manin

et al. 2024

Crystal Growth & Design

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The first ternary cocrystals of carbamazepine (CBZ) were successfully identified through a large-scale screening. A design strategy involved the use of an aliphatic dicarboxylic acid to link CBZ and a third component into a hydrogen-bonded trimeric unit. Out of the 10 dicarboxylic acids tested, only malonic acid produced a positive response in the attempt to obtain the CBZ ternary cocrystals with benzamide and picolinamide. The crystal structures of the novel ternary cocrystals obtained by vapor diffusion crystallization were determined by single-crystal X-ray diffraction. Structural analysis revealed that the ternary cocrystals are isostructural and exhibit the packing of trimers into ladder-like chains. The relationship between the CBZ binary and ternary cocrystals was confirmed by comparing the crystal structures. The cocrystal solubility method was applied to estimate the thermodynamic parameters of the ternary cocrystal formation. The negative values of the Gibbs free energy, enthalpy, and entropy indicate that the reaction of ternary cocrystal formation is a thermodynamically favored process and driven by enthalpy. Despite the isostructural nature, the physicochemical properties of the ternary cocrystals, including melting point and thermodynamic solubility, are strongly influenced by the variable coformer.

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“…The number of medications based on active pharmaceutical ingredients (API) in the form of salts and complexes has increased in recent decades, both in the total number and in the number of cations used [ 1 , 2 , 3 ]. This growth is related to ability of cations to tune physical chemical properties of an API, such as solubility or tabletability [ 4 , 5 , 6 , 7 , 8 ], and increased selectivity of their supramolecular binding with biological macromolecules and/or bioactivity [ 9 , 10 ], as well as to the existence of metallopharmaceuticals [ 11 , 12 , 13 , 14 ], metallodrugs, and bioMOFs with controlled release of API [ 15 , 16 , 17 , 18 , 19 , 20 ]. The Orange Book of Approved Drug Products with Therapeutic Equivalence Evaluations [ 21 ] contains information about salts of sodium, potassium, calcium, magnesium, iron, platinum, silver, and zinc.…”

Section: Introductionmentioning

confidence: 99%

Abiraterone Acetate Complexes with Biometals: Synthesis, Characterization in Solid and Solution, and the Nature of Chemical Bonding

Buikin,

Vologzhanina,

Novikov

et al. 2023

Pharmaceutics

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Abiraterone acetate (AbirAc) is the most used steroidal therapeutic agent for treatment of prostate cancer. The mainly hydrophobic molecular surface of AbirAc results in its poor solubility and plays an important role for retention of abiraterone in the cavity of the receptor formed by peptide chains and heme fragments. In order to evaluate the hydrolytic stability of AbirAc, to modify its solubility by formation of new solid forms and to model bonding of this medication with the heme, a series of d-metal complexes with AbirAc was obtained. AbirAc remains stable in water, acetonitrile, tetrahydrofuran, and ethanol, and readily interacts with dications as a terminal ligand to create discrete complexes, including [FePC(AbirAc)2] and [ZnTPP(AbirAc)] (H2PC = phthalocyanine and H2TPP = 5,10,15,20-tetraphenylporphyrine) models for ligand–receptor bonding. In reactions with silver(I) nitrate, AbirAc acts as a bridge ligand. Energies of chemical bonding between AbirAc and these cations vary from 97 to 235 kJ mol−1 and exceed those between metal atoms and water molecules. This can be indicative of the ability of abiraterone to replace solvent molecules in the coordination sphere of biometals in living cells, although the model [ZnTPP] complex remains stable in CDCl3, CD2Cl2, and 1,1,2,2-tetrachloroethane-d2 solvents and decomposes in polar dimethylsulfoxide-d6 and methanol-d4 solvents, as follows from the 1H DOSY spectra. Dynamics of its behavior in 1,1,2,2-tetrachloroethane-d2 were studied by ROESY and NMR spectra.

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Polymorphism of Carbamazepine Pharmaceutical Cocrystal: Structural Analysis and Solubility Performance

Cited by 8 publications

References 83 publications

Unraveling a Unique Metastable Phase of a Proxyphylline Cocrystal Exclusively Produced by Compressed Carbon Dioxide

Unraveling a Unique Metastable Phase of a Proxyphylline Cocrystal Exclusively Produced by Compressed Carbon Dioxide

Rational Design of the Carbamazepine Ternary Cocrystals

Abiraterone Acetate Complexes with Biometals: Synthesis, Characterization in Solid and Solution, and the Nature of Chemical Bonding

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