Formation of pharmaceutical salts and cocrystals <i>via</i> vapour-assisted tumbling (VAT) – a solvent efficient process

Stirk, Alexander Joseph; Souza, Fabio E. S.; Gerster, Jenny; Mir, Fatemeh M.; Karadeolian, Avedis; Rey, Allan W.

doi:10.1039/d1gc03683a

Cited by 9 publications

(14 citation statements)

References 46 publications

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“…Vapor-assisted tumbling (VAT) is a process modification of mechanochemistry with repurposed industry hardware. Pharmaceutical cocrystals were prepared by tumbling the coformers in a vaporized methanol solvent atmosphere inside an industrial rotary cone dryer (RCD) . Solid forms were crystallized using reusable/recyclable solvents in minimal volume, thus drastically lowering the environmental impact.…”

Section: Design and Methodology Of Pharmaceutical Cocrystalsmentioning

confidence: 99%

“…Gas tight RCDs can handle a wide variety of gaseous environments, including highly corrosive ones. For example, the commercial production of amorphous ziprasidone hydrochloride involves tumbling of the freebase drug in a HCl (g) chamber of RCD. Proton transfer in the solid–gas phase produces the hydrochloride salt in quantitative yield and excellent purity.…”

Section: Design and Methodology Of Pharmaceutical Cocrystalsmentioning

confidence: 99%

“…(f) Simple diagrams of a rotary cone dryer (top); VAT Mk.1 using a repurposed rotary evaporator (middle); and VAT Mk.10b apparatus with the same basic functions (bottom). Reprinted with permission from ref . Copyright 2022 Royal Society of Chemistry.…”

Section: Design and Methodology Of Pharmaceutical Cocrystalsmentioning

confidence: 99%

“…Pharmaceutical cocrystals were prepared by tumbling the coformers in a vaporized methanol solvent atmosphere inside an industrial rotary cone dryer (RCD). 229 Solid forms were crystallized using reusable/ recyclable solvents in minimal volume, thus drastically lowering the environmental impact. The pharmaceutical industry still prefers solvent-based methods despite the drawback of a higher cost and impact on environment, and high residual solvent levels.…”

Section: Preparation Methods Of Cocrystalsmentioning

confidence: 99%

“…230 Gas tight RCDs can handle a wide variety of gaseous environments, including highly corrosive ones. For example, the commercial production of amorphous ziprasidone hydrochloride 229…”

Section: Preparation Methods Of Cocrystalsmentioning

confidence: 99%

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Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

2022

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The subject of crystal engineering started in the 1970s with the study of topochemical reactions in the solid state. A broad chemical definition of crystal engineering was published in 1989, and the supramolecular synthon concept was proposed in 1995 followed by heterosynthons and their potential applications for the design of pharmaceutical cocrystals in 2004. This review traces the development of supramolecular synthons as robust and recurring hydrogen bond patterns for the design and construction of supramolecular architectures, notably, pharmaceutical cocrystals beginning in the early 2000s to the present time. The ability of a cocrystal between an active pharmaceutical ingredient (API) and a pharmaceutically acceptable coformer to systematically tune the physicochemical properties of a drug (i.e., solubility, permeability, hydration, color, compaction, tableting, bioavailability) without changing its molecular structure is the hallmark of the pharmaceutical cocrystals platform, as a bridge between drug discovery and pharmaceutical development. With the design of cocrystals via heterosynthons and prototype case studies to improve drug solubility in place (2000–2015), the period between 2015 to the present time has witnessed the launch of several salt–cocrystal drugs with improved efficacy and high bioavailability. This review on the design, synthesis, and applications of pharmaceutical cocrystals to afford improved drug products and drug substances will interest researchers in crystal engineering, supramolecular chemistry, medicinal chemistry, process development, and pharmaceutical and materials sciences. The scale-up of drug cocrystals and salts using continuous manufacturing technologies provides high-value pharmaceuticals with economic and environmental benefits.

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Section: Design and Methodology Of Pharmaceutical Cocrystalsmentioning

confidence: 99%

Section: Design and Methodology Of Pharmaceutical Cocrystalsmentioning

confidence: 99%

Section: Design and Methodology Of Pharmaceutical Cocrystalsmentioning

confidence: 99%

Section: Preparation Methods Of Cocrystalsmentioning

confidence: 99%

“…230 Gas tight RCDs can handle a wide variety of gaseous environments, including highly corrosive ones. For example, the commercial production of amorphous ziprasidone hydrochloride 229…”

Section: Preparation Methods Of Cocrystalsmentioning

confidence: 99%

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Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

2022

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SpeedMixing: Rapid Tribochemical Synthesis and Discovery of Pharmaceutical Cocrystals without Milling or Grinding Media**

et al. 2022

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We present SpeedMixing, a rapid blending technology, as an approach for fast mechanosynthesis and discovery of model pharmaceutical cocrystals through rapid spinning in the absence of bulk solvents and milling/grinding media. Syntheses of pharmaceutical cocrystals based on the active pharmaceutical ingredients (APIs) carbamazepine, dihydrocarbamazepine, and nicotinamide demonstrate SpeedMixing as a method for rapid, scalable, as well as controllable and selective synthesis of cocrystals, cocrystal polymorphs and stoichiomorphs, including the discovery of an unexpected methanol solvate of the archetypal cocrystal of carbamazepine and saccharin, which has eluded extensive screens over 20 years.

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SpeedMixing: Rapid Tribochemical Synthesis and Discovery of Pharmaceutical Cocrystals without Milling or Grinding Media**

et al. 2022

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show abstract

Formation of pharmaceutical salts and cocrystals via vapour-assisted tumbling (VAT) – a solvent efficient process

Abstract: Crystallisations on both the academic and industrial scale often use large volumes of solvent. In order decrease the environmental impact of such processes, new techniques must be discovered that increase...

Cited by 9 publications

References 46 publications

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

SpeedMixing: Rapid Tribochemical Synthesis and Discovery of Pharmaceutical Cocrystals without Milling or Grinding Media**

SpeedMixing: Rapid Tribochemical Synthesis and Discovery of Pharmaceutical Cocrystals without Milling or Grinding Media**

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