Cocrystal Dissociation in the Presence of Water: A General Approach for Identifying Stable Cocrystal Forms

Eddleston, Mark D.; Madusanka, Nadeesh; Jones, William

doi:10.1002/jps.24003

Cited by 45 publications

(46 citation statements)

References 33 publications

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“…It has been reported that caffeine co-crystals with a series of dicarboxylic acids dissociate upon exposure to humidity, which was supposed to be due to the partial dissolution of acid. 15 This was mainly attributed to solubility differences between caffeine and its co-formers. Similarly in the present study, caffeine/maleic acid 2:1 co-crystal was found to be unstable and dissociated providing caffeine as an additional product.…”

Section: Slurry Concentration Pxrd Resultsmentioning

confidence: 99%

Synthesis of Caffeine/Maleic Acid Co-crystal by Ultrasound-assisted Slurry Co-crystallization

Apshingekar

Aher

Kelly

et al. 2017

Journal of Pharmaceutical Sciences

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ABSTRACT:A green approach has been used for co-crystallization of non-congruent co-crystal pair of caffeinemaleic acid using water. Ultrasound is known to affect crystallization hence the effect of high power ultrasound on the ternary phase diagram has been investigated in detail using a slurry co-crystallization approach. A systematic investigation was performed to understand how the accelerated conditions during ultrasound assisted co-crystallization will affect different regions of the ternary phase diagram.Application of ultrasound showed considerable effect on the ternary phase diagram; principally on caffeine/maleic acid 2:1 (disappeared) and 1:1 co-crystal (narrowed) regions. Also, the stability regions for pure caffeine and maleic acid in water were narrowed in the presence of ultrasound, expanding the solution region. The observed effect of ultrasound on the phase diagram was correlated with solubility of caffeine and maleic acid and stability of co-crystal forms in water.

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Section: Slurry Concentration Pxrd Resultsmentioning

confidence: 99%

Synthesis of Caffeine/Maleic Acid Co-crystal by Ultrasound-assisted Slurry Co-crystallization

Apshingekar

Aher

Kelly

et al. 2017

Journal of Pharmaceutical Sciences

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“…[120][121][122] There have been a variety of theories postulated to explain hydrate formation for organic molecules. Thus, hydrates are more likely to form for: (a) a low hydrogen bond donor/hydrogen bond acceptor ratio; 123 (b) charged compounds; 124 (c) multiple counts of a functional group; 124 (d) high molecular weight compounds; 125 and (e) spatial constraints in hydrogen bonding.…”

Section: 12 21mentioning

confidence: 99%

Cocrystallization of Nutraceuticals

Sinha

Maguire

Lawrence

2015

Crystal Growth & Design

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Cocrystallization has emerged over the past decade as an attractive technique for modification of the physicochemical properties of compounds used as active pharmaceutical ingredients (APIs), complementing more traditional methods such as salt formation. Nutraceuticals, with associated health benefits and / or medicinal properties, are attractive as coformers due to their ready availability, known pharmacological profile and natural origin, in addition to offering a dual therapy approach. Successful studies of favorably altering the physicochemical properties of APIs through cocrystallization with nutraceuticals are highlighted in this review. Many of the key functional groups commonly seen in nutraceuticals (e.g. acids, phenols), underpin robust supramolecular synthons in crystal engineering. This review assesses the structural data available to date across a diverse range of nutraceuticals, both in pure form and in multicomponent materials, identifies the persistent supramolecular features present. This insight will ultimately enable predictive and controlled assembly of functional materials incorporating nutraceuticals together with APIs.

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“…Contact with water during oral administration often removes or alters coformers in cocrystals in the same manner as that under high-humidity storage conditions, leading to low-solubility and practically insoluble solids, such as API crystals, hydrate crystals, and other cocrystals. 57,76) Some cocrystals, such as those comprising CBZ, form metastable intermediates upon exposure to aqueous solutions.…”

Section: Solution-mediated Phase Transformation Andmentioning

confidence: 99%

Characterization and Quality Control of Pharmaceutical Cocrystals

Izutsu¹,

Koide²,

Takata

et al. 2016

Chem. Pharm. Bull.

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Recent active research and new regulatory guidance on pharmaceutical cocrystals have increased the rate of their development as promising approaches to improve handling, storage stability, and bioavailability of poorly soluble active pharmaceutical ingredients (APIs). However, their complex structure and the limited amount of available information related to their performance may require development strategies that differ from those of single-component crystals to ensure their clinical safety and efficacy. This article highlights current methods of characterizing pharmaceutical cocrystals and approaches to controlling their quality. Different cocrystal regulatory approaches between regions are also discussed. The physical characterization of cocrystals should include elucidating the structure of their objective crystal form as well as their possible variations (e.g., polymorphs, hydrates). Some solids may also contain crystals of individual components. Multiple processes to prepare pharmaceutical cocrystals (e.g., crystallization from solutions, grinding) vary in their applicable ingredients, scalability, and characteristics of resulting solids. The choice of the manufacturing method affects the quality control of particular cocrystals and their formulations. In vitro evaluation of the properties that govern clinical performance is attracting increasing attention in the development of pharmaceutical cocrystals. Understanding and mitigating possible factors perturbing the dissolution and/ or dissolved states, including solution-mediated phase transformation (SMPT) and precipitation from supersaturated solutions, are important to ensure the bioavailability of orally administrated lower-solubility APIs. The effect of polymer excipients on the performance of APIs emphasizes the relevance of formulation design for appropriate use.

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Cocrystal Dissociation in the Presence of Water: A General Approach for Identifying Stable Cocrystal Forms

Cited by 45 publications

References 33 publications

Synthesis of Caffeine/Maleic Acid Co-crystal by Ultrasound-assisted Slurry Co-crystallization

Synthesis of Caffeine/Maleic Acid Co-crystal by Ultrasound-assisted Slurry Co-crystallization

Cocrystallization of Nutraceuticals

Characterization and Quality Control of Pharmaceutical Cocrystals

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