2019
DOI: 10.1021/acs.oprd.9b00052
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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. Acetonemethanol (66.5-33.5 wt%) binary mixture was selected as a solvent based on the solubility of IMC reported earlier. Water was selected as an antisolvent based on the solubility of IMC measured in acetone-methanol-water mixtures at 25 °C. Unseeded and seeded antisolvent crystallization was carried out for two initial concentrat… Show more

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Cited by 13 publications
(40 citation statements)
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“…An increase is also observed in the yield when increasing the initial concentration. In previous work 29 The open-loop trajectory was magnified by ta factor of ten and the crystallization process was implemented on 5 L scale, to investigate the scalability of the direct design approach. Comparing the FBRM profiles and the product PSDs shown in Figure 11, a good agreement is observed between the two scale-up experiments and the original SSC experiment performed in the small scale.…”
Section: Supersaturation Controlmentioning
confidence: 99%
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“…An increase is also observed in the yield when increasing the initial concentration. In previous work 29 The open-loop trajectory was magnified by ta factor of ten and the crystallization process was implemented on 5 L scale, to investigate the scalability of the direct design approach. Comparing the FBRM profiles and the product PSDs shown in Figure 11, a good agreement is observed between the two scale-up experiments and the original SSC experiment performed in the small scale.…”
Section: Supersaturation Controlmentioning
confidence: 99%
“…During the presence of needle-shaped 6 crystals, the X-ray powder diffractograms (XRD) were measured off-line confirming only the presence of α-IMC. The XRD of the three forms are easily distinguished (Figure 1b In our previous work 28,29 antisolvent crystallization was performed in a 50 mL scale. An increased productivity was gained by using a ternary solvent system, where acetone-methanol (66.5-33.5 wt%) was used as solvent and water as an antisolvent.…”
mentioning
confidence: 91%
“…The antisolvent (AS) and solvent (S) addition rates were set to be and 2 mL/min, respectively, unless anything else is stated. Seeding with the desired γ-IMC was found essential in previous work 20,25,42 and was subsequently also used in this work. The seed crystals were added to the saturated solutions, and the FBRM count/s was left to settle with no temperature or antisolvent wt% change.…”
Section: Direct Nucleation Controlmentioning
confidence: 99%
“…Previously, the effect of increasing the seed surface area by altering the seed size was investigated by SSC and a twofold increase in supersaturation consumption with smaller seed size was also observed, which is in agreement with the finding of this work using DNC. 20,25,42 Using a larger seed size of 125-180 μm, compared to the smaller seeds with the size 45-63 μm, with antisolvent feed rate of 0.5 mL/min with same process parameters as a).…”
Section: Effect Of Seed Sizementioning
confidence: 99%
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