Sustained-Release Dual-Drug Ternary Salt Cocrystal of Piperazine Ferulate with Pyrazinamide: Synthesis, Structure, and Hirshfeld Surface Analysis

Yu, Xue-Zhao; Wang, Ling-Yang; Liu, Fang; Wu, Zhi‐Yong; Yan, Cui‐Wei

doi:10.1021/acs.cgd.9b01710

Cited by 30 publications

(18 citation statements)

References 55 publications

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“…Solvation effect on the dissolution process was studied via the HS analysis, , which provides the proportions of polar (hydrophilic) and nonpolar (hydrophobic) interactions in PTU and its cocrystals (Table ). The proportions of both hydrophilic and hydrophobic interactions in all cocrystal are improved, compared to that in PTU crystal.…”

Section: Results and Discussionmentioning

confidence: 99%

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

Xiao

Zhou

Hao

et al. 2021

Crystal Growth & Design

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

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Section: Results and Discussionmentioning

confidence: 99%

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

Xiao

Zhou

Hao

et al. 2021

Crystal Growth & Design

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“…A distinct advantage of the XPS technique is that a single-crystal-quality material is not required and the speed of measurement is relatively fast for rapid analysis in multiple samples, as is the case with API salt–cocrystal solid form screens . Carboxylic acids and pyridines are the most ubiquitous functional groups in APIs. − We are aware of the recent paper by Greczynski and Hultman and have checked that there are no calibration errors in our XPS assignment values. Multiple redeterminations of raw data and calibration values gave a difference of no more than 0.06–0.08 eV between repeated measurements on the same sample.…”

Section: Introductionmentioning

confidence: 96%

Can We Identify the Salt–Cocrystal Continuum State Using XPS?

Tothadi

Shaikh

Gupta

et al. 2021

Crystal Growth & Design

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X-ray photoelectron spectroscopy (XPS) is used to understand the nature of acid–base crystalline solids, to know whether the product is a salt (proton transfer, O–···H–N+) or a cocrystal (neutral adduct, O–H···N). The present study was carried out to explore if intermediate states of proton transfer from COOH to nitrogen (the proton resides between hydrogen bonded to O and N, O···H···N, quasi state) can be differentiated from a salt (complete proton transfer, N+–H··· O–) and cocrystal (no proton transfer, O–H···N) using N 1s XPS spectroscopy. The intermediate states of proton transfer arise when the pK a difference between the acid and the conjugate base is between −1 and 4, −1 < ΔpK a < 4, a situation common with COOH and pyridine functional groups present in drug molecules and pharmaceutically acceptable coformers. Complexes of pyridine N bases with aromatic COOH molecules in nine salts/cocrystals were cocrystallized, and their N 1s core binding energies in XPS spectra were measured. The proton state was analyzed by single-crystal X-ray diffraction for confirmation. Three new complexes were crystallized and analyzed by XPS spectra (without knowledge of their X-ray structures), to assess the predictive ability of XPS spectra in differentiating salt–cocrystal intermediate states against the extremities. The XPS results were subsequently confirmed by single-crystal X-ray data. Complexes of 3,5-dinitrobenzoic acid and isonicotinamide in 1:1 and 1:2 ratios exist as a salt and a salt–cocrystal continuum, respectively, as shown by the N 1s core binding energies. The proton states of the crystalline solids by XPS are in good agreement with the corresponding crystal structures. Other complexes, such as those of 3,5-dinitrobenzoic acid with 1,2-bis(4-pyridyl)ethylene, exhibit a salt–cocrystal continuum, maleic acids with 1,2-bis(4-pyridyl)ethylene and acridine are salts, 2-hydroxybenzoic acid and acridine is a salt, and the complex of 3,5-dinitrobenzoic acid and 3-hydroxypyridine is a salt and salt–cocrystal continuum, while fumaric acids with 1,2-bis(4-pyridyl)ethylene and acridine are cocrystals. Furthermore, three new acid–base complexes of 3,5-dinitrobenzoic acid with phenazine, 4-hydroxypyridine, and 4-cyanopyridine were studied initially by XPS and then confirmed by X-ray diffraction. In summary, since the N 1s binding energies cluster in a narrow range as cocrystals (398.7–398.9 eV) and salts (400.1–401.1 eV), it is clearly possible to differentiate between cocrystals and salts, but the salt–cocrystal continuum values in XPS spectra are clustered in an intermediate range of cocrystals and salts but overlap with those of cocrystal or salt binding energies.

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“…Various formulation strategies have been used to achieve sustained release profiles, such as polymeric matrices 162 , membrane-controlled 163 and osmotic pump drug delivery systems 164 . In the recent years, cocrystallization has been demonstrated as an alternative approach to sustain the drug release 165 , 166 , 167 , 168 , 169 , 170 . For example, the half-life of nicorandil (NCD) was prolonged by cocrystallizing with poorly soluble organic acids, such as 1-hydroxy-2-naphthoic acid (1-HNA) and salicylic acid (SA) 101 .…”

Section: Physicochemical Properties and Applications Of Cocrystalsmentioning

confidence: 99%

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

Guo

Sun

Chen

et al. 2021

Acta Pharmaceutica Sinica B

183

106

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

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Sustained-Release Dual-Drug Ternary Salt Cocrystal of Piperazine Ferulate with Pyrazinamide: Synthesis, Structure, and Hirshfeld Surface Analysis

Cited by 30 publications

References 55 publications

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

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

Can We Identify the Salt–Cocrystal Continuum State Using XPS?

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

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