The interplay between hydrogen bonds and stacking/T-type interactions in molecular cocrystals DOI Creative Commons
Aurora J. Cruz‐Cabeza, Peter R. Spackman, Amy V. Hall

и другие.

Communications Chemistry, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 2, 2024

Abstract Supramolecular synthon and hydrogen bond pairing approaches have influenced the understanding of cocrystal formation for decades, but are bonds really dominant interaction in cocrystals? To investigate this, an extensive analysis 1:1 two-component cocrystals Cambridge Structural Database was undertaken, revealing that stacking T-type interactions just as, if not more important than molecular cocrystals. A total 84% most common coformers dataset aromatic. When analysing dimers, only 20% consist solely strong bonds, with over 50% contacts involving interactions. Combining strength frequency, both stacking/T-type contribute equally to stabilisation lattices. Therefore, we state crystal engineering design concepts future should revolve around supramolecular via instead consider optimising bonding

Язык: Английский

Continuous Antisolvent Crystallization of Carbamazepine Dihydrate: Experiments and Modeling DOI Creative Commons

Vaishnavi G. Honavar,

Raj Wagh, Atul H. Bari

и другие.

Industrial & Engineering Chemistry Research, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Continuous antisolvent crystallization of carbamazepine dihydrate was carried out in three crystallizers, namely, stirred tank, oscillatory baffle crystallizer, and fluidic oscillator (with a helical coil). A generalized population balance model is developed using tanks-in-series framework. Options for providing multiple input locations internal recycling have been implemented. The kinetics were estimated by fitting the experimentally measured particle-size distributions concentration profiles. able to describe continuous experiments reasonably well all crystallizers considered this work. feed supersaturation found influence yield process 10% increase on increasing from 1.5 4.5. residence time both distribution overall (increasing 12 24 min, increased particle size 55 μm). Under same operating conditions, baffled crystallizer surpassed that tank approximately 10%. presented results will provide sound basis further work optimization carbamazepine.

Язык: Английский

Процитировано

2

One Size Fits All? Development of the CPOSS209 Data Set of Experimental and Hypothetical Polymorphs for Testing Computational Modeling Methods DOI Creative Commons
Louise S. Price, Matteo Paloni, Matteo Salvalaglio

и другие.

Crystal Growth & Design, Год журнала: 2025, Номер 25(9), С. 3186 - 3209

Опубликована: Апрель 28, 2025

Organic crystal structure prediction (CSP) studies have led to the rapid development of methods for predicting relative energies known and computer-generated structures. There is a compromise between level theoretical treatment, its reliability across different types organic systems, how accuracy depends on size shape unit cell, number structures that can be modeled at an affordable computational cost. We used our database studies, often performed as complement experimental screening, produce sets comprising 6 15 structures, covering polymorphs, observed packings closely related molecules, CSP-generated energetically competitive but distinct 20 molecules. These been chosen illustrate some issues need consideration in any lattice energy method, seeking generally applicable moderate-sized including small drug included crystallization reported polymorphs. In all examples, original CSP electronic calculations molecule give conformational anisotropic atom-atom model electrostatic intermolecular energy, combined with empirical "exp-6" repulsion dispersion energy. The are compared those obtained by reoptimizing periodic, plane-wave, dispersion-corrected density functional theory, specifically PBE TS correction, single point where many body (MBD) correction applied, example widely "workhorse" method. use this data set preliminary test modeling illustrated two Machine Learned Foundation Models, MACE-MP-0 MACE-OFF23. challenges putative polymorphs range their energies, possible agreement illustrated. Very similar molecules differ significantly observed, only partially reflecting polymorph screening experiments produced approaches based purely thermodynamic paradigm.

Язык: Английский

Процитировано

0

Novel Drug–Drug Cocrystalline Forms of Carbamazepine with Sulfacetamide: Preparation, Characterization, and In Vitro/In Vivo Performance Evaluation DOI Creative Commons
Denis E. Boycov, Ksenia V. Drozd, Alex N. Manin

и другие.

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

Процитировано

0

Pharmaceutical Cocrystals for Drug Delivery DOI
Ashwini Nangia

Burger's Medicinal Chemistry and Drug Discovery, Год журнала: 2025, Номер unknown, С. 1 - 62

Опубликована: Май 26, 2025

Abstract Pharmaceutical cocrystals offer the ability to tune solubility, permeability, tableting, and bioavailability of a solid, oral drug formulation without changing chemical structure molecule. Crystal engineering pharmaceutical salts via supramolecular heterosynthons with acceptable generally recognized as safe (GRAS) coformers provides platform technology for improving efficacy optimal delivery. With almost 90% drugs in Biopharmaceutics Classification System (BCS) class II IV suffering from low‐solubility and/or low‐permeability challenges, have provided an opportune intervention populating pipeline over past decade. From prototype cocrystal itraconazole‐succinic acid first salt‐cocrystal complex Entresto containing valsartan‐sacubitril, this review covers origins subject early 2000s peak growth curve model systems between 2005 2015, successful lab‐to‐market translation witnessed The combined application machine learning neural network tools is bringing speed accuracy research exercise designing drug–coformer therapeutic properties. This article snapshot summary latest trends leading discovery, development, continuous manufacturing.

Язык: Английский

Процитировано

0

The interplay between hydrogen bonds and stacking/T-type interactions in molecular cocrystals DOI Creative Commons
Aurora J. Cruz‐Cabeza, Peter R. Spackman, Amy V. Hall

и другие.

Communications Chemistry, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 2, 2024

Abstract Supramolecular synthon and hydrogen bond pairing approaches have influenced the understanding of cocrystal formation for decades, but are bonds really dominant interaction in cocrystals? To investigate this, an extensive analysis 1:1 two-component cocrystals Cambridge Structural Database was undertaken, revealing that stacking T-type interactions just as, if not more important than molecular cocrystals. A total 84% most common coformers dataset aromatic. When analysing dimers, only 20% consist solely strong bonds, with over 50% contacts involving interactions. Combining strength frequency, both stacking/T-type contribute equally to stabilisation lattices. Therefore, we state crystal engineering design concepts future should revolve around supramolecular via instead consider optimising bonding

Язык: Английский

Процитировано

1