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

Apshingekar, Prafulla P.; Aher, Suyog; Kelly, Adrian L.; Brown, Edward A.; Paradkar, Anant

doi:10.1016/j.xphs.2016.09.009

Cited by 33 publications

(26 citation statements)

References 16 publications

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“…The slurry technique is highly efficient for cocrystal screening with the advantage over other traditional methods that cocrystal formation is not limited to noncongruent solubility of cocrystal components and has a flexible range in terms of physical stability of the phase diagram and solvent selection approaches based on thermodynamically driven solution-mediated phase transformation. [20][21][22][23][24] Compared to cocrystal physicochemical characterizations, permeation studies of cocrystal have been limited even though membrane permeability is one of the most important characteristics determining drug performance during absorption or bioavailability. The cocrystals were to be non-toxic at concentrations up to 1 mM in in vitro cytotoxicity studies using Calu-3 cells and had better drug permeability than the drug alone by changing the efflux effect.…”

Section: Introductionmentioning

confidence: 99%

Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer

Suzuki

Muangnoi

Thaweesest

et al. 2019

Biological & Pharmaceutical Bulletin

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Oxyresveratrol (ORV) is a naturally extracted compound with many pharmacological activities. However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency Raman spectroscopy and thermal analysis. The solubility, dissolution and permeation studies across Caco-2 cell monolayers were conducted to evaluate the ORV samples. A screening study revealed that an ORV and citric acid (CTA) cocrystal formed by ethyl acetate-assisted grinding had characteristic PXRD peaks (14.0 and 16.5°) compared to those of ORV dihydrate used as a starting material. Low-frequency Raman measurements, with peaks at 100 cm 1 , distinguished potential cocrystals among three processing methods while conventional Raman could not. An endothermic melt (142.2°C) confirmed the formation of the novel crystalline complex. The solubility of the cocrystal in the dissolution media of pH 1.2 and 6.8 was approximately 1000 µg/mL, a 1.3-fold increase compared to ORV alone. In vitro cytotoxicity studies showed that the cocrystal and physical blend were not toxic at concentrations of 25 and 12.5 µM ORV, respectively. The ORV-CTA cocrystal enhanced the cellular transport of ORV across Caco-2 monolayers. Therefore, cocrystallization could be used to improve aqueous solubility and permeability, leading to better oral bioavailability of ORV.

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Section: Introductionmentioning

confidence: 99%

Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer

Suzuki

Muangnoi

Thaweesest

et al. 2019

Biological & Pharmaceutical Bulletin

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“…A slurry is a dispersion of solid particles in a liquid phase that comprises one or more solvents in which the chemical substance is not completely soluble. This process is based on generating supersaturation with respect to the cocrystal by subjecting a slurry of reactants to ultrasound pulses for accelerating the process [ 41 , 42 ].…”

Section: Techniques For Obtaining Cocrystalsmentioning

confidence: 99%

Obtaining Cocrystals by Reaction Crystallization Method: Pharmaceutical Applications

et al. 2021

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Cocrystals have gained attention in the pharmaceutical industry due to their ability to improve solubility, stability, in vitro dissolution rate, and bioavailability of poorly soluble drugs. Conceptually, cocrystals are multicomponent solids that contain two or more neutral molecules in stoichiometric amounts within the same crystal lattice. There are several techniques for obtaining cocrystals described in the literature; however, the focus of this article is the Reaction Crystallization Method (RCM). This method is based on the generation of a supersaturated solution with respect to the cocrystal, while this same solution is saturated or unsaturated with respect to the components of the cocrystal individually. The advantages of the RCM compared with other cocrystallization techniques include the ability to form cocrystals without crystallization of individual components, applicability to the development of in situ techniques for the screening of high quality cocrystals, possibility of large-scale production, and lower cost in both time and materials. An increasing number of scientific studies have demonstrated the use of RCM to synthesize cocrystals, mainly for drugs belonging to class II of the Biopharmaceutics Classification System. The promising results obtained by RCM have demonstrated the applicability of the method for obtaining pharmaceutical cocrystals that improve the biopharmaceutical characteristics of drugs.

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“…Noriyuki et al studied synthesis of corystals of stanolone and mestanolone using slurry crystallization 41 . Prafulla et al synthesized caffeine/maleic acid co-crystal by ultrasoundassisted slurry co-crystallization techniques 42 . Erizal et al prepared cocrystals of trimethoprim and sulfamethoxazole by slurry technique.…”

Section: Addition Of Solvent To Form Slurrymentioning

confidence: 99%

Co-Crystals: A Review

Chaudhari¹,

Nikam

Khatri³

et al. 2018

J. Drug Delivery Ther.

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In development of new product major constraints are poor aqueous solubility and low oral bioavailability. Crystallization is one the approach has been used for enhancement of solubility of poorly aqueous soluble drugs also helps to improve physicochemical properties such as melting point, tabletability, solubility, stability, bioavailability and permeability with preserving the pharmacological properties of the active pharmaceutical ingredient. Different methods have been used for the synthesis of cocrystal such as grinding, slurry, antisolvent, hot melt extrusion, sonocrystallization, supercritical fluid, spray drying etc. The article highlights the co-crystallization, its methods and significance.

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

Cited by 33 publications

References 16 publications

Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer

Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer

Obtaining Cocrystals by Reaction Crystallization Method: Pharmaceutical Applications

Co-Crystals: A Review

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