Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications

Acta Pharmaceutica Sinica B, Год журнала: 2021, Номер 11(8), С. 2537 - 2564

Опубликована: Март 23, 2021

Pharmaceutical cocrystals are multicomponent systems in which at least one component is an active pharmaceutical ingredient and the others pharmaceutically acceptable ingredients. Cocrystallization of a drug substance with coformer promising emerging approach to improve performance pharmaceuticals, such as solubility, dissolution profile, pharmacokinetics stability. This review article presents comprehensive overview cocrystals, including preparation methods, physicochemical properties, applications. Furthermore, some examples highlighted illustrate effect crystal structures on various aspects ingredients, physical stability, chemical mechanical optical bioavailability, sustained release therapeutic effect. will provide guidance for more efficient design manufacture desired properties

Язык: Английский

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Mechanochemistry: A Green Approach in the Preparation of Pharmaceutical Cocrystals

Pharmaceutics, Год журнала: 2021, Номер 13(6), С. 790 - 790

Опубликована: Май 25, 2021

Mechanochemistry is considered an alternative attractive greener approach to prepare diverse molecular compounds and has become important synthetic tool in different fields (e.g., physics, chemistry, material science) since ecofriendly procedure that can be carried out under solvent free conditions or the presence of minimal quantities (catalytic amounts). Being able substitute, many cases, classical solution reactions often requiring significant amounts solvents. These sustainable methods have had enormous impact on a great variety chemistry fields, including catalysis, organic synthesis, metal complexes formation, preparation multicomponent pharmaceutical solid forms, etc. In this sense, we are interested highlighting advantages mechanochemical obtaining cocrystals. Hence, review, describe discuss relevance procedures formation forms focusing Additionally, at end paper, collect chronological survey most representative scientific papers reporting synthesis

Язык: Английский

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Crystal engineering: from promise to delivery

Chemical Communications, Год журнала: 2023, Номер 59(95), С. 14052 - 14062

Опубликована: Янв. 1, 2023

Twenty years ago, I wrote a Chem. Commun. feature article entitled “ Crystal Engineering: where from? Where to? ”: an update is in order.

Язык: Английский

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Cocrystals of Propylthiouracil and Nutraceuticals toward Sustained-Release: Design, Structure Analysis, and Solid-State Characterization

Crystal Growth & Design, Год журнала: 2021, Номер 21(2), С. 1202 - 1217

Опубликована: Янв. 11, 2021

Propylthiouracil (PTU) is a clinically preferred drug to treat hyperthyroidism effectively. The sustained release of PTU necessary because the shortcomings rapid and hepatotoxicity. In this study, cocrystals with nutritional coformers were screened, four new cinnamic acid (CA), gentistic (GA), ellagic (EA), kaempferol (KA) discovered. characterized by single-crystal powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, electron microscopy. Hirshfeld surface analysis reduced density gradient reveal that weak van der Waals interactions play an essential role in crystal packing. stability test indicates all show excellent under accelerated storage conditions (40 °C 75% RH) over 12 weeks. Moreover, PTU-CA, PTU-EA, PTU-KA exhibit decreased solubility decelerated intrinsic dissolution rate (IDR). Among them, cocrystal shows best performance. Specifically, decrease up 77.32% pH 1.2 buffer 85.15% 6.8 buffer, lowest IDR 12.0% 20.8% buffers. According calculation result, sustained-release effect could be attributed enhanced lattice energies hydrophobic interaction. This work may useful design system via cocrystallization APIs have significant

Язык: Английский

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Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs

Pharmaceutics, Год журнала: 2022, Номер 14(10), С. 2003 - 2003

Опубликована: Сен. 21, 2022

Almost half of orally administered active pharmaceutical ingredients (APIs) have low solubility, which affects their bioavailability. In the last two decades, several alternatives been proposed to modify crystalline structure APIs improve solubility; these strategies consist inducing supramolecular structural changes in ingredients, such as amorphization and preparation co-crystals or polymorphs. Since many are thermosensitive, non-thermal emerging alternative techniques, mechanical activation by milling, become increasingly common a method for drug formulations. This review summarizes recent research preparing formulations (co-amorphous, co-crystals, polymorphs) through ball milling enhance physicochemical properties ingredients. report includes detailed experimental conditions (instrumentation, temperature, time, solvent, etc.), well bioavailability, structural, thermal stability data. The results description characterization techniques determine modifications resulting from transforming pure API into co-crystal, polymorph, co-amorphous system presented. Additionally, methodologies intermolecular interactions induced discussed explain obtained after process.

Язык: Английский

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Levofloxacin Cocrystal/Salt with Phthalimide and Caffeic Acid as Promising Solid-State Approach to Improve Antimicrobial Efficiency

Antibiotics, Год журнала: 2022, Номер 11(6), С. 797 - 797

Опубликована: Июнь 13, 2022

To overcome the issue of multidrug resistant (MDR) microbes, exploration ways to improve antimicrobial efficiency existing antibiotics is one promising approaches. In search synthons with higher efficiency, in current investigations, cocrystal and amorphous salt levofloxacin hemihydrate (LEV) were developed phthalimide (PTH) caffeic acid (CFA). New materials characterized help FT-IR, Raman spectroscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) thermogravimetric analysis (TGA). Shifting, attenuation, appearance/disappearance broadening bands observed FT-IR spectra as evidence required product. The PXRD pattern for LEV-PTH indicated while halo diffractogram LEV-CFA revealed nature. DSC/TG confirmed hydrated nature cocrystal/salt. dissolution rate activity against selected strains, K.pneumonia, E. coli S. typhi parent drug new material compared. zone inhibition (ZI) 5 µg was 30.4 + 0.36 (K. pneumonia), 26.33 0.35 (E. coli) 30.03 0.25 mm (S. typhi) (5 µg) same strains inhibited 33.96 ± 0.25, 31.66 27.93 0.40 mm, respectively. These novel formulations enhance well antibacterial are expected be potent MDR bacterial strains.

Язык: Английский

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Biodegradable nanocomposite poly(lactic acid) foams containing carvacrol-based cocrystal prepared by supercritical CO2 processing for controlled release in active food packaging

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 254, С. 127793 - 127793

Опубликована: Ноя. 4, 2023

Язык: Английский

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Levofloxacin and Ciprofloxacin Co-Crystals with Flavonoids: Solid-State Investigation for a Multitarget Strategy against Helicobacter pylori

Pharmaceutics, Год журнала: 2024, Номер 16(2), С. 203 - 203

Опубликована: Янв. 30, 2024

In this paper, we address the problem of antimicrobial resistance in case Helicobacter pylori with a crystal engineering approach. Two antibiotics fluoroquinolone class, namely, levofloxacin (LEV) and ciprofloxacin (CIP), have been co-crystallized flavonoids quercetin (QUE), myricetin (MYR), hesperetin (HES), resulting formation four co-crystals, LEV∙QUE, LEV∙MYR, LEV2∙HES, CIP∙QUE. The co-crystals were obtained from solution, slurry, or mechanochemical mixing reactants. LEV∙QUE LEV∙MYR initially as ethanol solvates LEV∙QUE∙xEtOH LEV∙MYR∙xEtOH, respectively, which upon thermal treatment yielded unsolvated forms. All characterized by powder X-ray diffraction gravimetric analysis. antibacterial performance CIP∙QUE comparison that physical mixtures separate components was tested via evaluation minimal inhibitory concentration (MIC) bactericidal (MBC). results indicate association co-formers, whether forming mixture active pharmaceutical ingredients (API), enhances activity fluoroquinolones, allowing them to significantly reduce amount API otherwise required display same against H. pylori.

Язык: Английский

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Variable stoichiometry cocrystals: occurrence and significance

CrystEngComm, Год журнала: 2021, Номер 23(26), С. 4583 - 4606

Опубликована: Янв. 1, 2021

Stoichiometric variation in organic cocrystals, their synthesis, structure elucidation and properties are discussed. Accountable reasons for the occurrence of such cocrystals emphasised.

Язык: Английский

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Thermodynamic Stability Is a Poor Indicator of Cocrystallization in Models of Organic Molecules

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(4), С. 2805 - 2815

Опубликована: Янв. 19, 2024

Cocrystallizing a given molecule with another can be useful for adjusting the physical properties of molecules in solid state. However, most combinations do not readily cocrystallize but form either one-component crystals or amorphous solids. Computational methods crystal structure prediction can, principle, identify thermodynamically stable cocrystal and thus predict if will not. pronounced polymorphism tendency many organic to disordered solids suggest that kinetic factors play an important role cocrystallization. The question remains: binary system has cocrystal, it indeed cocrystallize? To address this question, we simulate crystallization more than 2600 distinct pairs chiral model similar size 2D calculate accurate energy landscapes all them. Our analysis shows thermodynamic criteria alone are unreliable While vast majority cocrystals our simulations favorable, coformer systems have cocrystallize. We furthermore show cocrystallization rates increase 3-fold when coformers used well-ordered single-component crystals. results decisive cases.

Язык: Английский

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