Solid-state and particle size control of pharmaceutical cocrystals using atomization-based techniques

O'Sullivan, Aaron J; Long, Barry; Verma, Vivek; Ryan, Kevin M.; Padrela, Luís

doi:10.1016/j.ijpharm.2022.121798

Cited by 25 publications

(15 citation statements)

References 202 publications

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“…Mayzent ® cocrystal is thermodynamically stable and is manufactured by Novartis, Basel, Switzerland. Mayzent ® was approved by U.S. FDA in 2019 and available in tablet form [121][122][123].…”

Section: Mayzent ®mentioning

confidence: 99%

Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems

et al. 2023

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Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability present a significant challenge during their processing into final dosage forms. Cocrystallization of such APIs with suitable coformers is an efficient approach to mitigate the solubility and stability concerns. A considerable number of cocrystal-based products are currently being marketed and show an upward trend. However, to improve the API properties by cocrystallization, coformer selection plays a paramount role. Selection of suitable coformers not only improves the drug’s physicochemical properties but also improves the therapeutic effectiveness and reduces side effects. Numerous coformers have been used till date to prepare pharmaceutically acceptable cocrystals. The carboxylic acid-based coformers, such as fumaric acid, oxalic acid, succinic acid, and citric acid, are the most commonly used coformers in the currently marketed cocrystal-based products. Carboxylic acid-based coformers are capable of forming the hydrogen bond and contain smaller carbon chain with the APIs. This review summarizes the role of coformers in improving the physicochemical and pharmaceutical properties of APIs, and deeply explains the utility of afore-mentioned coformers in API cocrystal formation. The review concludes with a brief discussion on the patentability and regulatory issues related to pharmaceutical cocrystals.

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Section: Mayzent ®mentioning

confidence: 99%

Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems

et al. 2023

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“…Drug cocrystallization is widely approved as a promising and efficient cutting-edge technique for medicine creation and perfection. , Unlike traditional drug improvement methods, it attains the optimization and innovation of medicines solely by relying on embellishing the crystal lattices rather than altering the covalent structures and pharmacological actions of medications. − As a result, this technique has garnered growing attention from both academic and industrial sectors, along with relevant drug regulatory agencies. , Many cocrystal medicines have currently been approved for marketing and/or in various stages of clinical research and development . Against this background, although there have been some efforts to self-assemble AYL with various binary fatty acids based on the cocrystallization technology, which mainly focuses on the research of dissolubility enhancement, − relatively few investigations involving permeability behaviors have been reported .…”

Section: Introductionmentioning

confidence: 99%

“…19,20 Many cocrystal medicines have currently been approved for marketing and/or in various stages of clinical research and development. 21 Against this background, although there have been some efforts to self-assemble AYL with various binary fatty acids based on the cocrystallization technology, which mainly focuses on the research of dissolubility enhancement, 22−24 relatively few investigations involving permeability behaviors have been reported. 25 Furthermore, the impacts of different cocrystal coformers (CCFs) on the antiviral effectiveness of AYL have almost been disregarded in all existing cocrystal systems.…”

Section: ■ Introductionmentioning

confidence: 99%

Directed Self-Assembly with Gallic Acid Provides First Phenolic Acid Cocrystals for the Antiviral Drug Acyclovir toward Increasing Pharmaceutical Features and Synergy: A Theoretical and Experimental Integration Research

Zhang

et al. 2023

Crystal Growth & Design

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To achieve new breakthroughs in the development of synergistic antiviral medication cocrystals of acyclovir (AYL) with phenolic acids, a cocrystallization-driven strategy for optimizing the physicochemical properties and increasing the antiviral efficacy is proposed. This method emphasizes the structural features and medicinal value together with the dominant properties of gallic acid (GLA) to promote both solubility and permeability of AYL by cocrystallizing GLA into AYL's lattice; meanwhile, the antiviral ability of ALY can be greatly increased by activating the antiviral potential of GLA and utilizing the synergistic antiviral activity of both in cocrystal formation. Guided by this idea, the first AYL-phenolic acid cocrystal, AYL-GLA-2H 2 O, is orientationally constructed and fully characterized. The accurate cocrystal structure revealed by single-crystal X-ray diffraction indicates that the entry of GLA into the AYL lattice has disrupted the homodimer of AYL itself, leading to the formation of a hydrophobic heterodimer between AYL and GLA molecules, coupled with an aqueous tetramer, thus endowing the cocrystal with both hydrophilic and hydrophobic characteristics. Such structural feature induces a concurrent enhancement in dissolubility and permeability of the cocrystal compared with the parent medicine. These observations can be strongly supported by density functional theory-based theoretical investigations involving molecular electrostatic potential, Hirshfeld surface, frontier molecular orbital, and Gibbs solvation free energy. Interestingly, the perfected AYL's properties along with the stimulated antiviral activity of GLA enable the two ingredients in the cocrystal to display synergistic antiviral activity against the herpes simplex virus with a cooperativity index of less than 1, contributing to enhancing the antiviral ability. Thus, this contribution not only highlights the effectiveness of combining theory with experiment to solve AYL's issues via the cocrystallization-driven method but fills in the gaps from previous studies on AYL-phenolic acid cocrystals with synergistic antiviral effects.

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“…Electrospraying (ES) and spray drying (SD) are emerging techniques for cocrystal and polymorph screening. − SD is a particle processing technique that is already well established in the pharmaceutical industry and allows for modification of particle properties, for example, to aid with suitable dispersibility for pulmonary drug delivery . Both methods involve dispersing a liquid into fine droplets that dry within the processing time, and the main factor promoting nucleation and crystal growth is the rapid concentration increase.…”

Section: Introductionmentioning

confidence: 99%

Metronidazole Cocrystal Polymorphs with Gallic and Gentisic Acid Accessed through Slurry, Atomization Techniques, and Thermal Methods

Dyba,

Wiącek,

Nowak

et al. 2023

Crystal Growth & Design

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In this study, key features of metronidazole (MNZ) cocrystal polymorphs with gallic acid (GAL) and gentisic acid (GNT) were elucidated. Solvent-mediated phase transformation experiments in 30 solvents with varying properties were employed to control the polymorphic behavior of the MNZ cocrystal with GAL. Solvents with relative polarity (RP) values above 0.35 led to cocrystal I°, the thermodynamically stable form. Conversely, solvents with RP values below 0.35 produced cocrystal II, which was found to be only 0.3 kJ mol–1 less stable in enthalpy. The feasibility of electrospraying, including solvent properties and process conditions required, and spray drying techniques to control cocrystal polymorphism was also investigated, and these techniques were found to facilitate exclusive formation of the metastable MNZ-GAL cocrystal II. Additionally, the screening approach resulted in a new, high-temperature polymorph I of the MNZ-GNT cocrystal system, which is enantiotropically related to the already known form II°. The intermolecular energy calculations, as well as the 2D similarity between the MNZ-GAL polymorphs and the 3D similarity between MNZ-GNT polymorphs, rationalized the observed transition behaviors. Furthermore, the evaluation of virtual cocrystal screening techniques identified molecular electrostatic potential calculations as a supportive tool for coformer selection.

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Solid-state and particle size control of pharmaceutical cocrystals using atomization-based techniques

Cited by 25 publications

References 202 publications

Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems

Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems

Directed Self-Assembly with Gallic Acid Provides First Phenolic Acid Cocrystals for the Antiviral Drug Acyclovir toward Increasing Pharmaceutical Features and Synergy: A Theoretical and Experimental Integration Research

Metronidazole Cocrystal Polymorphs with Gallic and Gentisic Acid Accessed through Slurry, Atomization Techniques, and Thermal Methods

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