Crystallization of cephradine polymorphs and hydrates from mixed solvents of methanol and water

Publikation: Konferencebidrag uden forlag/tidsskriftPaperForskning

Resumé

Cephradine is a first-generation cephalosporin antibiotic and can be used to treat different infectious diseases. It has been reported that cephradine can form at least 4 anhydrous polymorphs, one mono-hydrate and one dihydrate [1]–[3], which leads to significant challenges in the crystallization pro-cess as the product has to be crystallized with the desired solid form and the preferred particle size and shape.
In this work, the relative stability of the anhydrate/monohydrate cephradine (CPA/CPH) as a func-tion of temperature and water activity in the surrounding medium was investigated by measuring the solubility of CPA/CPH in different methanol and water mixtures at varying temperatures from 15 to 55 °C. The solid recovered from the solubility measurement was analyzed by Raman spectros-copy and X-ray Powder Diffraction (XRPD), to identify if a solvent-mediated solid form transfor-mation had occurred. It was observed that the CPH transformed to an anhydrous form at methanol mole fractions greater than 0.65-0.80 depending on the temperature, and that this anhydrous form is a different polymorph than the anhydrous cephradine purchased from Sigma-Aldrich. Subsequently, crystallization behavior of cephradine polymorphs and hydrates are studied in batch cooling crystal-lizations from water and methanol mixtures. Effects of different operating parameters, such as cool-ing rate, different solvent composition and seeding, on the formation of the solid form and the par-ticulate properties have been studied.
The obtained results can be used to predict the relative stability of the anhydrate/monohydrate cephradine (CPA/CPH) at different temperatures and water activity in the surrounding medium. Furthermore, the obtained knowledge regarding the crystallization behavior of the different solid forms of cephradine can be used in the design and development of crystallization processes to yield the desired solid phase of cephradine.
OriginalsprogEngelsk
Publikationsdato31. maj 2018
StatusUdgivet - 31. maj 2018
BegivenhedBIWIC 2018: 25th International Workshop on Industrial Crystallization - University of Rouen, Rouen, Frankrig
Varighed: 5. sep. 20187. sep. 2018

Konference

KonferenceBIWIC 2018
LokationUniversity of Rouen
LandFrankrig
ByRouen
Periode05/09/201807/09/2018

Fingeraftryk

Cephradine
Crystallization
Hydrates
Polymorphism
Methanol
Water
Solubility
Temperature
Cephalosporins
X ray powder diffraction
Particle size
Cooling
Crystals

Citer dette

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title = "Crystallization of cephradine polymorphs and hydrates from mixed solvents of methanol and water",
abstract = "Cephradine is a first-generation cephalosporin antibiotic and can be used to treat different infectious diseases. It has been reported that cephradine can form at least 4 anhydrous polymorphs, one mono-hydrate and one dihydrate [1]–[3], which leads to significant challenges in the crystallization pro-cess as the product has to be crystallized with the desired solid form and the preferred particle size and shape.In this work, the relative stability of the anhydrate/monohydrate cephradine (CPA/CPH) as a func-tion of temperature and water activity in the surrounding medium was investigated by measuring the solubility of CPA/CPH in different methanol and water mixtures at varying temperatures from 15 to 55 °C. The solid recovered from the solubility measurement was analyzed by Raman spectros-copy and X-ray Powder Diffraction (XRPD), to identify if a solvent-mediated solid form transfor-mation had occurred. It was observed that the CPH transformed to an anhydrous form at methanol mole fractions greater than 0.65-0.80 depending on the temperature, and that this anhydrous form is a different polymorph than the anhydrous cephradine purchased from Sigma-Aldrich. Subsequently, crystallization behavior of cephradine polymorphs and hydrates are studied in batch cooling crystal-lizations from water and methanol mixtures. Effects of different operating parameters, such as cool-ing rate, different solvent composition and seeding, on the formation of the solid form and the par-ticulate properties have been studied.The obtained results can be used to predict the relative stability of the anhydrate/monohydrate cephradine (CPA/CPH) at different temperatures and water activity in the surrounding medium. Furthermore, the obtained knowledge regarding the crystallization behavior of the different solid forms of cephradine can be used in the design and development of crystallization processes to yield the desired solid phase of cephradine.",
author = "Iben {\O}stergaard and Haiyan Qu",
year = "2018",
month = "5",
day = "31",
language = "English",
note = "BIWIC 2018 : 25th International Workshop on Industrial Crystallization ; Conference date: 05-09-2018 Through 07-09-2018",

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Østergaard, I & Qu, H 2018, 'Crystallization of cephradine polymorphs and hydrates from mixed solvents of methanol and water' Paper fremlagt ved BIWIC 2018, Rouen, Frankrig, 05/09/2018 - 07/09/2018, .

Crystallization of cephradine polymorphs and hydrates from mixed solvents of methanol and water. / Østergaard, Iben ; Qu, Haiyan.

2018. Afhandling præsenteret på BIWIC 2018, Rouen, Frankrig.

Publikation: Konferencebidrag uden forlag/tidsskriftPaperForskning

TY - CONF

T1 - Crystallization of cephradine polymorphs and hydrates from mixed solvents of methanol and water

AU - Østergaard, Iben

AU - Qu, Haiyan

PY - 2018/5/31

Y1 - 2018/5/31

N2 - Cephradine is a first-generation cephalosporin antibiotic and can be used to treat different infectious diseases. It has been reported that cephradine can form at least 4 anhydrous polymorphs, one mono-hydrate and one dihydrate [1]–[3], which leads to significant challenges in the crystallization pro-cess as the product has to be crystallized with the desired solid form and the preferred particle size and shape.In this work, the relative stability of the anhydrate/monohydrate cephradine (CPA/CPH) as a func-tion of temperature and water activity in the surrounding medium was investigated by measuring the solubility of CPA/CPH in different methanol and water mixtures at varying temperatures from 15 to 55 °C. The solid recovered from the solubility measurement was analyzed by Raman spectros-copy and X-ray Powder Diffraction (XRPD), to identify if a solvent-mediated solid form transfor-mation had occurred. It was observed that the CPH transformed to an anhydrous form at methanol mole fractions greater than 0.65-0.80 depending on the temperature, and that this anhydrous form is a different polymorph than the anhydrous cephradine purchased from Sigma-Aldrich. Subsequently, crystallization behavior of cephradine polymorphs and hydrates are studied in batch cooling crystal-lizations from water and methanol mixtures. Effects of different operating parameters, such as cool-ing rate, different solvent composition and seeding, on the formation of the solid form and the par-ticulate properties have been studied.The obtained results can be used to predict the relative stability of the anhydrate/monohydrate cephradine (CPA/CPH) at different temperatures and water activity in the surrounding medium. Furthermore, the obtained knowledge regarding the crystallization behavior of the different solid forms of cephradine can be used in the design and development of crystallization processes to yield the desired solid phase of cephradine.

AB - Cephradine is a first-generation cephalosporin antibiotic and can be used to treat different infectious diseases. It has been reported that cephradine can form at least 4 anhydrous polymorphs, one mono-hydrate and one dihydrate [1]–[3], which leads to significant challenges in the crystallization pro-cess as the product has to be crystallized with the desired solid form and the preferred particle size and shape.In this work, the relative stability of the anhydrate/monohydrate cephradine (CPA/CPH) as a func-tion of temperature and water activity in the surrounding medium was investigated by measuring the solubility of CPA/CPH in different methanol and water mixtures at varying temperatures from 15 to 55 °C. The solid recovered from the solubility measurement was analyzed by Raman spectros-copy and X-ray Powder Diffraction (XRPD), to identify if a solvent-mediated solid form transfor-mation had occurred. It was observed that the CPH transformed to an anhydrous form at methanol mole fractions greater than 0.65-0.80 depending on the temperature, and that this anhydrous form is a different polymorph than the anhydrous cephradine purchased from Sigma-Aldrich. Subsequently, crystallization behavior of cephradine polymorphs and hydrates are studied in batch cooling crystal-lizations from water and methanol mixtures. Effects of different operating parameters, such as cool-ing rate, different solvent composition and seeding, on the formation of the solid form and the par-ticulate properties have been studied.The obtained results can be used to predict the relative stability of the anhydrate/monohydrate cephradine (CPA/CPH) at different temperatures and water activity in the surrounding medium. Furthermore, the obtained knowledge regarding the crystallization behavior of the different solid forms of cephradine can be used in the design and development of crystallization processes to yield the desired solid phase of cephradine.

M3 - Paper

ER -