Measurements and Correlation of Timolol Maleate Solubility in Biobased Neat and Binary Solvent Mixtures

2-methyltetrahydrofuran; 2-propanol; Binary solvent mixtures; Bio-based solvents; Crystallization process; Isosorbide; Pure solvents; Relative deviations; Solubility data; Timolol maleate; Chemistry (all); Chemical Engineering (all)

Abstract :

[en] A crucial factor in the development of sustainable crystallization processes is the use of biobased solvents, which, in turn, necessitates a comprehensive understanding of the solubility profiles of solid compounds in biobased solvents. The solubility of timolol maleate (TIM), used to treat glaucoma, was measured in commercial biobased solvents at temperatures ranging from 278.15 to 333.15 K using the polythermal method. Its solubility was determined in eight neat biobased solvents (acetone, 1-butanol, Cyrene, dimethyl isosorbide (DMI), ethanol, 2-methyltetrahydrofuran (2-MeTHF), 2-propanol, and water) and three binary solvent mixtures (ethanol + 2-propanol, ethanol + 2-MeTHF, and ethanol + DMI). It was demonstrated that the solubility of TIM increases with temperature in the pure solvents and solvent mixtures. Furthermore, the solubility of TIM decreases in ethanol with increasing 2-propanol, 2-MeTHF, or DMI content, which may act as antisolvents. The experimental solubility data of TIM in the pure solvents and binary solvent mixtures were correlated using the modified Apelblat, Yaws, and λh equations. The correlated solubility data agree well with the experimental results, indicated by the small relative deviation and average relative deviation (ARD %) values. The correlated and experimentally determined solubility data provide crucial information for the design of sustainable crystallization processes for TIM.

Disciplines :

Chemical engineering

Author, co-author :

Zimmermann, Lennart ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States ; Bioseparation Engineering Group, Technical University of Munich, Garching, Germany

Lee, Hung Lin ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States

Koishybay, Aibolat ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States

Vlaar, Cornelis P. ; Department of Pharmaceutical Sciences, University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico

Monbaliu, Jean-Christophe ; Université de Liège - ULiège > Molecular Systems (MolSys)

Romañach, Rodolfo J. ; Department of Chemistry, University of Puerto Rico - Mayagüez, Mayagüez, Puerto Rico

Noor-E-Alam, Md. ; Department of Mechanical and Industrial Engineering, College of Engineering, Center for Health Policy and Healthcare Research, Northeastern University, Boston, United States

Myerson, Allan S. ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States

Stelzer, Torsten ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, United States ; Department of Pharmaceutical Sciences, University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico ; Crystallization Design Institute, Molecular Sciences Research Center, University of Puerto Rico, San Juan, Puerto Rico

Language :

English

Title :

Measurements and Correlation of Timolol Maleate Solubility in Biobased Neat and Binary Solvent Mixtures

Publication date :

13 June 2024

Journal title :

Journal of Chemical and Engineering Data

ISSN :

0021-9568

eISSN :

1520-5134

Publisher :

American Chemical Society (ACS)

Volume :

Issue :

Pages :

2369 - 2379

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://pubs.acs.org/doi/pdf/10.1021/acs.jced.4c00060

Funding text :

This research was supported by the U.S. Food and Drug Administration under the FDA BAA-22-00123 program, Award Number 75F40122C00192.

Available on ORBi :

since 09 July 2025

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