Physicochemical Characterization and Structural Evaluation of a Specific 2:1 Cocrystal of Naproxen–Nicotinamide

Ando, Soichiro; Kikuchi, Junko; Fujimura, Yuko; Ida, Yasuo; Higashi, Kenjirou; Moribe, Kunikazu; Yamamoto, Keiji

doi:10.1002/jps.23158

Cited by 58 publications

(62 citation statements)

References 25 publications

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“…In this method, the species are first dissolved in an organic solvent and the addition of CO 2 to the solution induces a decrease of the solute's solubility and provokes hereafter the species precipitation. In case of S-naproxen / nicotinamide system, the produced cocrystals exhibited the same stoichiometry and the same bonding pattern than cocrystals formed by more conventional methods 12,13 . When the naproxen:nicotinamide ratio of processed solutions was deviated from the 2:1 stoichiometric ratio, e.g 3:1 and 1:1, the same cocrystal phase was recovered and, thanks to the CO 2 procedure, even these solutions yielded powders of 98 ± 2% cocrystal content.…”

Section: Introductionmentioning

confidence: 78%

“…As a result, cocrystals of naproxen with picolinamide, isonicotinamide and nicotinamide were successfully synthesized and characterized. Nicotinamide being FDA-approved as GRAS (Generally Regarded as Safe), Ando et al further focused on the naproxen:nicotinamide system and characterized the cocrystal structure by solid-state nuclear magnetic resonance and single-crystal X-ray diffraction 13 . An essential feature of naproxen is its chirality.…”

Section: Introductionmentioning

confidence: 99%

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Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO₂ Antisolvent Crystallization

Neurohr

Marchivie

Lecomte

et al. 2015

Crystal Growth & Design

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Cocrystallization of naproxen racemic mixture and nicotinamide was investigated in this work, using compressed CO 2 as antisolvent. A novel racemic cocrystal structure containing both enantiomers of naproxen linked to nicotinamide has been produced thanks to CO 2 antisolvent batch crystallization process. The structure of the molecular complex and the analysis of its intermolecular interactions were investigated by Single Crystal X-ray Diffraction (SCXRD) and Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR). The antisolvent feed rate was found to have a direct influence on the cocrystallization outcome. The racemic cocrystal was obtained at slow and moderate CO 2 feed rate, while very fast introduction of CO 2 resulted in the formation of a mixture of chiral cocrystals (conglomerate). Cross-seedings, thermal analysis and Temperature Resolved X-Ray Powder Diffraction (TR-XRPD) were used to probe the relationship between the different phases. In addition, all powders produced with CO 2 technology were obtained as cocrystal-pure, without significant excess of naproxen or nicotinamide homocrystals. ABSTRACTCocrystallization of naproxen racemic mixture and nicotinamide was investigated in this work, using compressed CO 2 as antisolvent. A novel racemic cocrystal structure containing both enantiomers of naproxen linked to nicotinamide has been produced thanks to CO 2 antisolvent batch crystallization process. The structure of the molecular complex and the analysis of its intermolecular interactions were investigated by Single Crystal X-ray Diffraction (SCXRD) andAttenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR). The antisolvent feed rate was found to have a direct influence on the cocrystallization outcome. The racemic cocrystal was obtained at slow and moderate CO 2 feed rate, while very fast introduction of CO 2 resulted in the formation of a mixture of chiral cocrystals (conglomerate). Cross-seedings, thermal analysis and Temperature Resolved X-Ray Powder Diffraction (TR-XRPD) were used to probe the relationship between the different phases. In addition, all powders produced with CO 2 technology were obtained as cocrystal-pure, without significant excess of naproxen or nicotinamide homocrystals.

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Section: Introductionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO₂ Antisolvent Crystallization

Neurohr

Marchivie

Lecomte

et al. 2015

Crystal Growth & Design

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show abstract

“…33,35) Solid-state NMR associated with new data processing methods, such as cross-polarization magic angle spinning, offers a more practical characterization approach. 36) Methods such as FT-IR vibrational analysis of carboxyl groups, 33) Raman spectroscopy, and X-ray photoelectron spectroscopy combined with solid-state density functional theory (DFT) have also been applied to the characterization. 37) FDA guidance clearly separates regulatory pathways for salts and cocrystals.…”

Section: )mentioning

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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“…4) evidences the formation of the cocrystal by the presence of characteristic peaks at 5.4°, 12.3°, 17.3°that are distinct from the specific peaks of pure naproxen and pure nicotinamide. The strong anisotropy of the produced plate-like particles is responsible for the difference of the peaks intensity compared to that in published patterns [44,41] because of preferred orientations effects. The ATR-FTIR analyses (Fig.…”

Section: Solutionmentioning

confidence: 85%

“…Castro et al [43] reported that naproxen formed cocrystals with the water-soluble nicotinamide at the molar ratio of 2:1 by the Kofler contact method and the liquid-assisted ballmilling process. Later, Ando et al [44] prepared the cocrystal by solvent drop grinding, clarified the crystal structure and characterized the physicochemical properties. The NPX 2 :NCTA cocrystals showed improved dissolution properties compared to single NPX or NPX-NCTA physical mixture, and was less hygroscopic than the sodium salt of NPX.…”

Section: Introductionmentioning

confidence: 99%

Challenge of the supercritical antisolvent technique SAS to prepare cocrystal-pure powders of naproxen-nicotinamide

Neurohr

Erriguible

Laugier

et al. 2016

Chemical Engineering Journal

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Physicochemical Characterization and Structural Evaluation of a Specific 2:1 Cocrystal of Naproxen–Nicotinamide

Cited by 58 publications

References 25 publications

Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO₂ Antisolvent Crystallization

Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO₂ Antisolvent Crystallization

Characterization and Quality Control of Pharmaceutical Cocrystals

Challenge of the supercritical antisolvent technique SAS to prepare cocrystal-pure powders of naproxen-nicotinamide

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Physicochemical Characterization and Structural Evaluation of a Specific 2:1 Cocrystal of Naproxen–Nicotinamide

Cited by 58 publications

References 25 publications

Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO2 Antisolvent Crystallization

Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO2 Antisolvent Crystallization

Characterization and Quality Control of Pharmaceutical Cocrystals

Challenge of the supercritical antisolvent technique SAS to prepare cocrystal-pure powders of naproxen-nicotinamide

Contact Info

Product

Resources

About

Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO₂ Antisolvent Crystallization

Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO₂ Antisolvent Crystallization