Virtual Screening, Structural Analysis, and Formation Thermodynamics of Carbamazepine Cocrystals

Pharmaceutics, Год журнала: 2023, Номер 15(3), С. 836 - 836

Опубликована: Март 3, 2023

In this study, the existing set of carbamazepine (CBZ) cocrystals was extended through successful combination drug with positional isomers acetamidobenzoic acid. The structural and energetic features CBZ 3- 4-acetamidobenzoic acids were elucidated via single-crystal X-ray diffraction followed by QTAIMC analysis. ability three fundamentally different virtual screening methods to predict correct cocrystallization outcome for assessed based on new experimental results obtained in study data available literature. It found that hydrogen bond propensity model performed worst distinguishing positive negative experiments 87 coformers, attaining an accuracy value lower than random guessing. method utilizes molecular electrostatic potential maps machine learning approach named CCGNet exhibited comparable terms prediction metrics, albeit latter resulted superior specificity overall while requiring no time-consuming DFT computations. addition, formation thermodynamic parameters newly evaluated using temperature dependences Gibbs energy. reactions between selected coformers be enthalpy-driven, entropy being statistically from zero. observed difference dissolution behavior aqueous media thought caused variations their stability.

Язык: Английский

---

Polymorphism of Carbamazepine Pharmaceutical Cocrystal: Structural Analysis and Solubility Performance

Pharmaceutics, Год журнала: 2023, Номер 15(6), С. 1747 - 1747

Опубликована: Июнь 15, 2023

Polymorphism is a common phenomenon among single- and multicomponent molecular crystals that has significant impact on the contemporary drug development process. A new polymorphic form of carbamazepine (CBZ) cocrystal with methylparaben (MePRB) in 1:1 molar ratio as well drug's channel-like containing highly disordered coformer molecules have been obtained characterized this work using various analytical methods, including thermal analysis, Raman spectroscopy, single-crystal high-resolution synchrotron powder X-ray diffraction. Structural analysis solid forms revealed close resemblance between novel II previously reported I [CBZ + MePRB] (1:1) terms hydrogen bond networks overall packing arrangements. The was found to belong distinct family isostructural CBZ cocrystals coformers similar size shape. Form appeared be related by monotropic relationship, being proven thermodynamically more stable phase. dissolution performance both polymorphs aqueous media significantly enhanced when compared parent CBZ. However, considering superior thermodynamic stability consistent profile, discovered seems promising reliable for further pharmaceutical development.

Язык: Английский

---

A Perspective on the Permeability of Cocrystals/Organic Salts of Oral Drugs

Molecular Pharmaceutics, Год журнала: 2024, Номер 21(10), С. 4860 - 4911

Опубликована: Сен. 16, 2024

According to the BCS classification system, differentiation of drugs is based on two essential parameters solubility and permeability, meaning latter as pivotal former in creating marketable pharmaceutical products. Nevertheless, indispensable role permeability cocrystal profiles has not been sufficiently cherished, which can be most probably attributed principal reasons. First, responsibility may more user-friendly

Язык: Английский

---

An outlook on permeability escalation through cocrystallization for developing pharmaceuticals with improved biopharmaceutical properties

Journal of Drug Delivery Science and Technology, Год журнала: 2022, Номер 76, С. 103757 - 103757

Опубликована: Сен. 5, 2022

Язык: Английский

---

Exploring uracil derivatives: synthesis, crystal structure insights, and antibacterial activity

CrystEngComm, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Four uracil derivatives were synthesized and analyzed to reveal how molecular modifications influence crystal packing, stability, antibacterial properties.

Язык: Английский

---

Theoretical Examination and Exploration of Intermolecular Interactions and Chemical Reactivity of Nitrofurantoin‐4‐Hydroxy Benzamide Co‐Crystal

ChemistrySelect, Год журнала: 2025, Номер 10(19)

Опубликована: Май 1, 2025

Abstract This study explores the molecular, electronic, and chemical modifications of nitrofurantoin (NF) upon co‐crystallization with 4‐hydroxybenzamide (4HBAM), resulting in formation a NF–4HBAM (1:2) co‐crystal. Molecular geometries were optimized using Density Functional Theory (DFT) at B3LYP/6–31G(d,p) level via Gaussian09 to evaluate impact on NF's physicochemical properties. The co‐crystal exhibited enhanced reactivity, characterized by increased polarizability, reduced kinetic stability, greater softness compared individual components, indicating stronger intermolecular interactions more compact molecular arrangement. Electrostatic Potential (MEP) surface mapping revealed distinct electrophilic nucleophilic reactive sites. Natural Bond Orbital (NBO) analysis confirmed significant conjugative hyperconjugative interactions, second‐order stabilization energies supporting presence strong hydrogen bonding. also demonstrated promising non‐linear optical (NLO) behavior, evidenced high dipole moment (μ = 12.3556), polarizability (α –30.1834 × 10⁻ 2 ⁴ e.s.u), first‐order hyperpolarizability (β₀ 1.589 3 ⁰ suggesting potential optoelectronic applications. Additionally, Fermi energy NF‐4HBAM is 2.8364 eV, observed through density states (DOS) analysis, which highlights electronic performance. These findings underscore role tuning pharmaceutical functional

Язык: Английский

---

Novel Drug–Drug Cocrystalline Forms of Carbamazepine with Sulfacetamide: Preparation, Characterization, and In Vitro/In Vivo Performance Evaluation

Pharmaceutics, Год журнала: 2025, Номер 17(5), С. 678 - 678

Опубликована: Май 21, 2025

Objectives: Drug–drug cocrystallization represents a promising approach for the development of novel combination drugs with improved physicochemical and biopharmaceutical properties. The aim present research is to prepare drug-drug cocrystalline forms antiepileptic drug carbamazepine (CBZ) sulfacetamide (SCTM). Methods: CBZ cocrystal methanol solvate hydrate were prepared via solvent evaporation technique characterized by single crystal X-ray diffraction, differential scanning calorimetry thermogravimetric analysis. Results: Single-crystal diffraction thermal analysis revealed that multicomponent solids are isostructural, wherein molecule does not play structure-forming role. To optimize synthesis [CBZ+SCTM+H2O] (1:1:0.7), binary ternary phase diagrams constructed in acetonitrile at 25 °C. A thorough investigation behavior aqueous solution showed pH dissolution medium exerted significant effect on stability solubility (1:1:0.7). According diffusion experiments buffer 6.5, an enhanced rate flux CBZ. Pharmacokinetic studies rabbits exhibited comparable bioavailability parent Conclusions: Overall, this work reports preparation hydrate, which can be considered as alternative solid form oral usage, possessing additive pharmacological effect.

Язык: Английский

---

How Molecular Packing Affects the Thermodynamic Parameters of Cocrystal Formation: The Case of Carbamazepine Cocrystals

Crystal Growth & Design, Год журнала: 2023, Номер 24(1), С. 252 - 261

Опубликована: Ноя. 30, 2023

In the present work, thermodynamic aspects related to driving force of cocrystal formation and their stability were studied for a series 1:1 carbamazepine (CBZ) cocrystals. The parameters (Gibbs free energy, enthalpy, entropy) CBZ cocrystals with cinnamic acid, salicylic 2,4-dihydroxybenzoic 2,6-dihydroxybenzoic acid determined from solubilities parent compounds in acetonitrile at 293–313 K. correlation between solubility products intrinsic values coformers was used estimate standard Gibbs energy 4-hydroxybenzoic acid. relation molecular packing features observed. crystal lattice energies calculated by PIXEL. trend enthalpies dispersion terms found. competitive grinding reactions evaluate relative results found be good agreement experimentally formation.

Язык: Английский

---

A Combination of Virtual and Experimental Screening Tools for the Prediction of Nitrofurantoin Multicomponent Crystals with Pyridine Derivatives

Crystals, Год журнала: 2023, Номер 13(7), С. 1022 - 1022

Опубликована: Июнь 28, 2023

Thirty-four binary systems of nitrofurantoin with pyridine derivatives were analyzed by combining virtual (molecular complementarity prediction and hydrogen bond propensity calculations) experimental (liquid-assisted grinding) screening methods. A new modification the calculation method (the integrated method) significantly improved efficiency was proposed. Novel cocrystals 3-aminopyridine 2-(1H-Imidazol-2-yl)pyridine discovered. The crystal structures determined from single-crystal X-ray diffraction data, patterns studied in conjunction Molecular Electrostatic Potential maps components. cocrystal found to exist two polymorphic modifications. origins different stability forms rationalized both terms total lattice enthalpy free energy derived periodic DFT-D3 calculations non-covalent interaction distribution crystal.

Язык: Английский

---

Research Progress on the Molecular Mechanism of Polymorph Nucleation in Solution: A Perspective from Research Mentality and Technique

Crystals, Год журнала: 2023, Номер 13(8), С. 1206 - 1206

Опубликована: Авг. 3, 2023

Based on the importance of polymorphic regulation, molecular mechanism nucleation has been widely concerned. This review begins by introducing development and limitations theory for organic small molecule crystals, followed a summary general research mentality adopted current researchers. Moreover, progress its application to regulation crystal forms are discussed. In addition, scientific tools study is also summarized, including experimental characterization computational simulation, providing reference relevant Finally, according main defects ideas, models directions prospects recommendations put forward.

Язык: Английский

---