Antisolvent Crystallization of Indomethacin from a Ternary Solvent System with High Productivity, Better Polymorphism, and Particle Size Control

Chandrakant Ramkrishna Malwade*, Haiyan Qu

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Antisolvent crystallization of indomethacin (IMC), a nonsteroidal anti-inflammatory drug, from a ternary solvent system (acetone–methanol–water) has been investigated in this work. The acetone–methanol (66.5–33.5 wt %) binary mixture was selected as a solvent on the basis of the solubility of IMC reported earlier. Water was selected as an antisolvent on the basis of the solubility of IMC measured in acetone–methanol–water mixtures at 25 °C. Unseeded and seeded antisolvent crystallization was carried out for two initial concentrations of IMC (C0,1 and C0,2) with the stepwise addition of antisolvent. The acetone solvate of IMC was crystallized during the unseeded experiments, while the desired γ-IMC was obtained with a bimodal particle size distribution (PSD) during the experiments seeded with γ-IMC. A significant increase in the productivity was observed because of increased crystal yield and faster crystallization kinetics as compared to those of the crystallization processes reported earlier for the production of γ-IMC. Finally, the feasibility of IMC particle size tuning through the solvent–antisolvent (dissolution–growth) addition cycles was demonstrated successfully.
OriginalsprogEngelsk
TidsskriftOrganic Process Research & Development
Vol/bind23
Udgave nummer5
Sider (fra-til)968-976
ISSN1083-6160
DOI
StatusUdgivet - 17. maj 2019

Fingeraftryk

polymorphism
Crystallization
Polymorphism
productivity
Indomethacin
Productivity
Particle size
crystallization
solubility
particle size distribution
acetone
binary mixtures
drugs
tuning
Solubility
cycles
kinetics
Crystallization kinetics
water
Acetone

Citer dette

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title = "Antisolvent Crystallization of Indomethacin from a Ternary Solvent System with High Productivity, Better Polymorphism, and Particle Size Control",
abstract = "Antisolvent crystallization of indomethacin (IMC), a nonsteroidal anti-inflammatory drug, from a ternary solvent system (acetone–methanol–water) has been investigated in this work. The acetone–methanol (66.5–33.5 wt {\%}) binary mixture was selected as a solvent on the basis of the solubility of IMC reported earlier. Water was selected as an antisolvent on the basis of the solubility of IMC measured in acetone–methanol–water mixtures at 25 °C. Unseeded and seeded antisolvent crystallization was carried out for two initial concentrations of IMC (C0,1 and C0,2) with the stepwise addition of antisolvent. The acetone solvate of IMC was crystallized during the unseeded experiments, while the desired γ-IMC was obtained with a bimodal particle size distribution (PSD) during the experiments seeded with γ-IMC. A significant increase in the productivity was observed because of increased crystal yield and faster crystallization kinetics as compared to those of the crystallization processes reported earlier for the production of γ-IMC. Finally, the feasibility of IMC particle size tuning through the solvent–antisolvent (dissolution–growth) addition cycles was demonstrated successfully.",
keywords = "antisolvent crystallization, indomethacin, particle size distribution, polymorphism, solubility",
author = "Malwade, {Chandrakant Ramkrishna} and Haiyan Qu",
year = "2019",
month = "5",
day = "17",
doi = "10.1021/acs.oprd.9b00052",
language = "English",
volume = "23",
pages = "968--976",
journal = "Organic Process Research and Development",
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publisher = "American Chemical Society",
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}

Antisolvent Crystallization of Indomethacin from a Ternary Solvent System with High Productivity, Better Polymorphism, and Particle Size Control. / Malwade, Chandrakant Ramkrishna; Qu, Haiyan.

I: Organic Process Research & Development, Bind 23, Nr. 5, 17.05.2019, s. 968-976.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Antisolvent Crystallization of Indomethacin from a Ternary Solvent System with High Productivity, Better Polymorphism, and Particle Size Control

AU - Malwade, Chandrakant Ramkrishna

AU - Qu, Haiyan

PY - 2019/5/17

Y1 - 2019/5/17

N2 - Antisolvent crystallization of indomethacin (IMC), a nonsteroidal anti-inflammatory drug, from a ternary solvent system (acetone–methanol–water) has been investigated in this work. The acetone–methanol (66.5–33.5 wt %) binary mixture was selected as a solvent on the basis of the solubility of IMC reported earlier. Water was selected as an antisolvent on the basis of the solubility of IMC measured in acetone–methanol–water mixtures at 25 °C. Unseeded and seeded antisolvent crystallization was carried out for two initial concentrations of IMC (C0,1 and C0,2) with the stepwise addition of antisolvent. The acetone solvate of IMC was crystallized during the unseeded experiments, while the desired γ-IMC was obtained with a bimodal particle size distribution (PSD) during the experiments seeded with γ-IMC. A significant increase in the productivity was observed because of increased crystal yield and faster crystallization kinetics as compared to those of the crystallization processes reported earlier for the production of γ-IMC. Finally, the feasibility of IMC particle size tuning through the solvent–antisolvent (dissolution–growth) addition cycles was demonstrated successfully.

AB - Antisolvent crystallization of indomethacin (IMC), a nonsteroidal anti-inflammatory drug, from a ternary solvent system (acetone–methanol–water) has been investigated in this work. The acetone–methanol (66.5–33.5 wt %) binary mixture was selected as a solvent on the basis of the solubility of IMC reported earlier. Water was selected as an antisolvent on the basis of the solubility of IMC measured in acetone–methanol–water mixtures at 25 °C. Unseeded and seeded antisolvent crystallization was carried out for two initial concentrations of IMC (C0,1 and C0,2) with the stepwise addition of antisolvent. The acetone solvate of IMC was crystallized during the unseeded experiments, while the desired γ-IMC was obtained with a bimodal particle size distribution (PSD) during the experiments seeded with γ-IMC. A significant increase in the productivity was observed because of increased crystal yield and faster crystallization kinetics as compared to those of the crystallization processes reported earlier for the production of γ-IMC. Finally, the feasibility of IMC particle size tuning through the solvent–antisolvent (dissolution–growth) addition cycles was demonstrated successfully.

KW - antisolvent crystallization

KW - indomethacin

KW - particle size distribution

KW - polymorphism

KW - solubility

U2 - 10.1021/acs.oprd.9b00052

DO - 10.1021/acs.oprd.9b00052

M3 - Journal article

VL - 23

SP - 968

EP - 976

JO - Organic Process Research and Development

JF - Organic Process Research and Development

SN - 1083-6160

IS - 5

ER -