Pharmaceutical Cocrystals: A Perspective on Development and Scale-up of Solution Cocrystallization

Crystal Growth & Design, Journal Year: 2023, Volume and Issue: 23(11), P. 7558 - 7581

Published: July 31, 2023

Pharmaceutical cocrystals represent an emergent class of successful materials designed based on crystal engineering principles, in which the limitations extant drugs are addressed. Though number newly reported is increasing exponentially, scale-up cocrystallization process has not received enough attention. Solution techniques offer scalable processes that can utilize conventional crystallization machinery and analytical technologies. The presence multiple components competing kinetics starting as well cocrystal make harder to study control. This perspective emphasizes importance multicomponent phase diagrams for identifying operating regions solution discusses effects various parameters kinetics. It also covers intermolecular interactions involved development, methods, quality control pharmaceuticals. Furthermore, role Design Experiment Quality by scaling up efficiently highlighted. A systematic decision tree been proposed production promising using solution-based techniques, effectively address current challenges large-scale help bring these potential market near future.

Language: Английский

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Recent Advances in Co-Former Screening and Formation Prediction of Multicomponent Solid Forms of Low Molecular Weight Drugs

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(9), P. 2174 - 2174

Published: Aug. 22, 2023

Multicomponent solid forms of low molecular weight drugs, such as co-crystals, salts, and co-amorphous systems, are a result the combination an active pharmaceutical ingredient (API) with pharmaceutically acceptable co-former. These can enhance physicochemical pharmacokinetic properties APIs, making them increasingly interesting important in recent decades. Nevertheless, predicting formation API multicomponent early stages formulation development be challenging, it often requires significant time resources. To address this, empirical computational methods have been developed to help screen for potential co-formers more efficiently accurately, thus reducing number laboratory experiments needed. This review provides comprehensive overview current screening prediction forms, covering both crystalline states (co-crystals salts) amorphous (co-amorphous). Furthermore, discusses advances emerging trends methods, particular focus on artificial intelligence.

Language: Английский

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Deep Eutectic Solvents as Agents for Improving the Solubility of Edaravone: Experimental and Theoretical Considerations

Molecules, Journal Year: 2024, Volume and Issue: 29(6), P. 1261 - 1261

Published: March 12, 2024

In this study, both practical and theoretical aspects of the solubility edaravone (EDA) in Deep Eutectic Solvents (DESs) were considered. The some media, including water, can be limited, which creates need for new efficient environmentally safe solvents. EDA was measured spectrophotometrically complex intermolecular interactions within systems studied with COSMO-RS framework. Of four DES systems, three outperformed most classical organic solvent, namely dichloromethane, comprising choline chloride triethylene glycol, acting as hydrogen bond donor (HBD), a 1:2 molar proportion yielding highest EDA. Interestingly, addition specific amount water further increased solubility. Theoretical analysis revealed that pure or solutions high content, stacking is responsible self-aggregation lower On other hand, presence HBDs leads to formation clusters EDA, reducing self-aggregation. However, stoichiometric three-molecular EDA–HBD–water formed, explains why also act co-solvent. probability type complexes related affinity components, exceeds all possible complexes.

Language: Английский

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Water-mediated phase transformations of posaconazole: An intricate jungle of crystal forms

European Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: 195, P. 106722 - 106722

Published: Feb. 7, 2024

Posaconazole is a broad-spectrum antifungal agent exhibiting rich polymorphism. Up to now, total of fourteen different crystal forms have been reported, sometimes with an ambiguous nomenclature, but less known about their properties and stability relationships. Investigating the solid-state drug compound essential identify most stable form under working conditions prevent risk undesired solid-phase transformations processing storage. In this paper, we study posaconazole polymorphism by providing description its polymorphs, hydrates, solvates. Powder X-ray diffraction (PXRD), dynamic vapor sorption (DVS), spectroscopic thermal techniques were employed characterize forms. addition, in aqueous suspensions studied means Raman microscopy. Surprisingly, found that Form S, contained marketed oral suspension, not water. S readily converts more hydrate, i.e. A, after storage water for two weeks. commercial formulation conversion between prevented presence polysorbate 80. Such insights into stabilizing excipient effects beyond particle dispersion are critical formulators.

Language: Английский

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Prioritizing Computational Cocrystal Prediction Methods for Experimental Researchers: A Review to Find Efficient, Cost-Effective, and User-Friendly Approaches

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12045 - 12045

Published: Nov. 9, 2024

Pharmaceutical cocrystals offer a versatile approach to enhancing the properties of drug compounds, making them an important tool in formulation and development by improving therapeutic performance patient experience pharmaceutical products. The prediction involves using computational theoretical methods identify potential cocrystal formers understand interactions between active ingredient coformers. This process aims predict whether two or more molecules can form stable structure before performing experimental synthesis, thus saving time resources. In this review, commonly used are first overviewed then evaluated based on three criteria: efficiency, cost-effectiveness, user-friendliness. Based these considerations, we suggest researchers without strong experiences which tools should be tested as step workflow rational design cocrystals. However, optimal choice depends specific needs resources, combining from different categories powerful approach.

Language: Английский

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High-Throughput Encapsulated Nanodroplet Screening for Accelerated Co-Crystal Discovery

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A high-throughput nanoscale co-crystallisation approach is presented, that combines automation and small scale to enable the exploration of conditions, resulting in 30 new binary, ternary quaternary co-crystals.

Language: Английский

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Discovery of Cilnidipine Cocrystals with Enhanced Dissolution by the Use of Computational Tools and Semiautomatic High-Throughput Screening

Crystal Growth & Design, Journal Year: 2025, Volume and Issue: 25(10), P. 3374 - 3385

Published: April 29, 2025

Cocrystals are an attractive option for overcoming drug limitations, such as a low dissolution rate and absorption of poorly water-soluble compounds. Nevertheless, the discovery new cocrystals remains trial-and-error approach in which hundreds coformers several experimental methods often tested. To streamline cocrystal screening, computational can be used to select most likely form cocrystal, while high-throughput screening (HTS) approaches rapidly screen them experimentally. In this manuscript, extremely soluble cilnidipine (solubility ≈30 ng/mL, 0.06 μM) was successfully discovered by applying HTS approaches. Only one resulted from with total 52 coformers, whereby molecular complementarity ranked coformer (p-toluenesulfonamide) at third position list. Dissolution studies conducted on blank FaSSIF (fasted-state simulated intestinal fluid) pH 6.5 revealed enhanced maximum achieved supersaturation equal seven times solubility crystalline drug. rates were compared better mechanistic understanding dissolution-supersaturation-precipitation behavior. The case rare occurrence emphasized importance using joint enable successful identification pharmaceutical development.

Language: Английский

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In silico cocrystal screening using COSMO-RS: A rapid and efficient approach for solubility prediction and crystal engineering

Journal of Molecular Liquids, Journal Year: 2025, Volume and Issue: unknown, P. 127841 - 127841

Published: June 1, 2025

Language: Английский

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Intermolecular Interactions as a Measure of Dapsone Solubility in Neat Solvents and Binary Solvent Mixtures

Materials, Journal Year: 2023, Volume and Issue: 16(18), P. 6336 - 6336

Published: Sept. 21, 2023

Dapsone is an effective antibacterial drug used to treat a variety of conditions. However, the aqueous solubility this limited, as its permeability. This study expands available data pool for dapsone by measuring in several pure organic solvents: N-methyl-2-pyrrolidone (CAS: 872-50-4), dimethyl sulfoxide 67-68-5), 4-formylmorpholine 4394-85-8), tetraethylene pentamine 112-57-2), and diethylene glycol bis(3-aminopropyl) ether 4246-51-9). Furthermore, proposes use intermolecular interactions molecular descriptors predict neat solvents binary mixtures using machine learning models. An ensemble regressors was used, including support vector machines, random forests, gradient boosting, neural networks. Affinities solvent molecules were calculated COSMO-RS input model training. Due polymorphic nature dapsone, fusion are not available, which prohibits direct calculations. Therefore, consonance approach tested, allows indirect estimation properties. Unfortunately, resulting accuracy unsatisfactory. In contrast, developed showed high predictive potential. work documents that characterized solute-solvent contacts can be considered valuable modeling wealth encoded information sufficient predictions new systems, those experimental measurements thermodynamic properties unavailable.

Language: Английский

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Novel nimesulide multicomponent solid forms: screening, synthesis, thermoanalytical study and characterization

Journal of Thermal Analysis and Calorimetry, Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Abstract Nimesulide (NMS) is a widely used non-steroidal anti-inflammatory drug, however, presents low aqueous solubility. One way to overcome the solubility issue of drugs altering their solid forms through some approaches like cocrystals, coamorphous, and eutectic mixtures. The purpose this work was prospect new multicomponent NMS. A virtual-experimental cocrystal screening carried out COSMOquick software mechanochemical experiments. Alternatively, dual-drug coamorphous systems were investigated by quench cooling and/or cryomilling processes. All samples characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) infrared spectroscopy (FTIR). results confirmed successful synthesis NMS-piperazine (NMS-PPZ), two mixtures NMS-gentisic acid (NMS-GSA) NMS-isoniazid (NMS-INH), as well novel drug-drug systems. compositions determined binary solid–liquid phase diagram construction Tamman’s triangle plot. Nimesulide-omeprazole (NMS-OMP) system found be stable for at least 120 days in dry conditions. with bicalutamide (NMS-BICA) prepared process more than that obtained cryomilling. Finally, dissolution rate study demonstrated NMS are dissolved relatively faster pure drug.

Language: Английский

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