Feedback control of a ternary solvent system with increased productivity

Iben Østergaard*, Botond Szilagyi, Zoltan K. Nagy, Heidi Lopez de Diego, Haiyan Qu

*Kontaktforfatter for dette arbejde

Publikation: Konferencebidrag uden forlag/tidsskriftPaperForskning

Resumé

In this work, increased productivity of the model compound indomethacin (IMC) was obtained using the ternary solvent mixture of acetone-methanol-water system compared to the pure sol-vents. IMC is a nonsteroidal anti-inflammatory drug and it has been reported to form five polymorphs and several solvates, which lead to significant challenges in the crystallization process as the product has to be crystallized with the desired solid form and the preferred parti-cle size and shape. However, the metastable α-IMC having needle-like crystal shape and the thermodynamically most stable γ-IMC having plate-like crystal shape are most commonly ob-served.
The crystallization behaviour of IMC is studied by antisolvent crystallization and was carried out with acetone-methanol (66.5-33.5 wt%) as solvent and water as an antisolvent. The benefits of using different feedback strategies with various process analytical technologies (PATs) were investigated to control the crystal size distribution (CSD) and simultaneously obtaining the de-sired polymorph.
The obtained results show how feedback control of a ternary solvent mixture increases produc-tivity and simultaneously ensures a unimodal CSD and desired polymorphism.
OriginalsprogEngelsk
Publikationsdatosep. 2019
StatusUdgivet - sep. 2019
BegivenhedThe International Workshop on Industrial Crystallization - Vistec, Rayong, Thailand
Varighed: 25. aug. 201927. nov. 2019
Konferencens nummer: 26

Konference

KonferenceThe International Workshop on Industrial Crystallization
Nummer26
LokationVistec
LandThailand
ByRayong
Periode25/08/201927/11/2019

Fingeraftryk

Indomethacin
Feedback control
Productivity
Crystallization
Polymorphism
Crystals
Acetone
Methanol
Water
Vents
Polymethyl Methacrylate
Needles
Anti-Inflammatory Agents
Feedback
Pharmaceutical Preparations

Citer dette

Østergaard, I., Szilagyi, B., Nagy, Z. K., Lopez de Diego, H., & Qu, H. (2019). Feedback control of a ternary solvent system with increased productivity. Paper præsenteret på The International Workshop on Industrial Crystallization, Rayong, Thailand.
Østergaard, Iben ; Szilagyi, Botond ; Nagy, Zoltan K. ; Lopez de Diego, Heidi ; Qu, Haiyan. / Feedback control of a ternary solvent system with increased productivity. Paper præsenteret på The International Workshop on Industrial Crystallization, Rayong, Thailand.
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Østergaard, I, Szilagyi, B, Nagy, ZK, Lopez de Diego, H & Qu, H 2019, 'Feedback control of a ternary solvent system with increased productivity', Paper fremlagt ved The International Workshop on Industrial Crystallization, Rayong, Thailand, 25/08/2019 - 27/11/2019.

Feedback control of a ternary solvent system with increased productivity. / Østergaard, Iben; Szilagyi, Botond; Nagy, Zoltan K.; Lopez de Diego, Heidi; Qu, Haiyan.

2019. Paper præsenteret på The International Workshop on Industrial Crystallization, Rayong, Thailand.

Publikation: Konferencebidrag uden forlag/tidsskriftPaperForskning

TY - CONF

T1 - Feedback control of a ternary solvent system with increased productivity

AU - Østergaard, Iben

AU - Szilagyi, Botond

AU - Nagy, Zoltan K.

AU - Lopez de Diego, Heidi

AU - Qu, Haiyan

PY - 2019/9

Y1 - 2019/9

N2 - In this work, increased productivity of the model compound indomethacin (IMC) was obtained using the ternary solvent mixture of acetone-methanol-water system compared to the pure sol-vents. IMC is a nonsteroidal anti-inflammatory drug and it has been reported to form five polymorphs and several solvates, which lead to significant challenges in the crystallization process as the product has to be crystallized with the desired solid form and the preferred parti-cle size and shape. However, the metastable α-IMC having needle-like crystal shape and the thermodynamically most stable γ-IMC having plate-like crystal shape are most commonly ob-served.The crystallization behaviour of IMC is studied by antisolvent crystallization and was carried out with acetone-methanol (66.5-33.5 wt%) as solvent and water as an antisolvent. The benefits of using different feedback strategies with various process analytical technologies (PATs) were investigated to control the crystal size distribution (CSD) and simultaneously obtaining the de-sired polymorph.The obtained results show how feedback control of a ternary solvent mixture increases produc-tivity and simultaneously ensures a unimodal CSD and desired polymorphism.

AB - In this work, increased productivity of the model compound indomethacin (IMC) was obtained using the ternary solvent mixture of acetone-methanol-water system compared to the pure sol-vents. IMC is a nonsteroidal anti-inflammatory drug and it has been reported to form five polymorphs and several solvates, which lead to significant challenges in the crystallization process as the product has to be crystallized with the desired solid form and the preferred parti-cle size and shape. However, the metastable α-IMC having needle-like crystal shape and the thermodynamically most stable γ-IMC having plate-like crystal shape are most commonly ob-served.The crystallization behaviour of IMC is studied by antisolvent crystallization and was carried out with acetone-methanol (66.5-33.5 wt%) as solvent and water as an antisolvent. The benefits of using different feedback strategies with various process analytical technologies (PATs) were investigated to control the crystal size distribution (CSD) and simultaneously obtaining the de-sired polymorph.The obtained results show how feedback control of a ternary solvent mixture increases produc-tivity and simultaneously ensures a unimodal CSD and desired polymorphism.

M3 - Paper

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Østergaard I, Szilagyi B, Nagy ZK, Lopez de Diego H, Qu H. Feedback control of a ternary solvent system with increased productivity. 2019. Paper præsenteret på The International Workshop on Industrial Crystallization, Rayong, Thailand.