Influence of solvent choice and operating conditions on Chlorzoxazone crystal shape and size
DOI:
https://doi.org/10.1590/s2175-97902023e20918Keywords:
Chlorzoxazone, Solubility, Cooling crystallization, Solvent choice, Crystal shape, Size distributionAbstract
Solubility of pharmaceutical drugs in organic solvents is one of the important parameters to understand the equilibrium concentration of solute-solvent, which helps optimize and design crystallization conditions to obtain the desired product crystals. In the present study, Chlorzoxazone (CHZ) is used as a model pharmaceutical compound to investigate the equilibrium solubility, the influence of solvent and the operating conditions on the shape, and the size distribution. The solubility of CHZ is determined in organic solvents like Isopropanol, Ethanol, and 2-Ethoxyethylacetate, Ethylacetate and Ethyllactate using shake flask method from -5ºC to 60ºC. The solubility of CHZ in these solvents shows an increasing trend as the temperature increases in the following order: ethyllactate + water (0.5+0.5) < ethylacetate < isopropanol < ethanol < 2-ethoxyethylacetate < ethyllactate + water (0.75+0.25). The solvents, isopropanol, ethanol, and ethyl lactate, produce needle-shaped crystals, while 2-ethoxyethylacetate and ethyl acetate tend to produce plate shaped crystals. CHZ crystals obtained from 2-ethoxyethylacetate tend to have plate shaped crystals with a lower aspect ratio and are selected for batch cooling crystallization experiments performed at different cooling rates, and agitation. It is found that the agitation at 300 rpm and the cooling rate 0.2ºC/min produce more uniform crystal size distribution.
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Acquah C, Karunanithi AT, Cagnetta M, Achenie LEK, Suib SL. Linear models for prediction of ibuprofen crystal morphology based on hydrogen bonding propensities. Fluid Phase Equilib. 2009;277(1):73-80.
Aragon DM, Rosas JE, Martinez F. Thermodynamic study of the solubility of ibuprofen in acetone and dichloromethane. Braz J Pharm Sci. 2010;46(2):227-35.
Baka E, Comer JEA, Takács-Novák K. Study of equilibrium solubility measurement by saturation shake-flask method using hydrochlorothiazide as model compound. J Pharm Biomed Anal. 2008;46(2):335-41.
Brittain HG. Polymorphism in pharmaceutical solids. CRC Press. 2016.
Chen J, Sarma B, Evans JMB, Myerson AS. Pharmaceutical crystallization. Cryst Growth Des. 2011;11(4):887-95.
Croker DM, Kelly DM, Horgan DE, Hodnett BK, Lawrence SE, Moynihan HA, et al. Demonstrating the influence of solvent choice and crystallization conditions on phenacetin crystal habit and particle size distribution. Org Process Res Dev. 2015;19(12):1826-36.
Fevotte G, Klein JP. A new policy for the estimation of the course of supersaturation in batch crystallization. Can J Chem Eng. 1996;74(3):372-84.
Gracin S, Rasmuson ÅC. Solubility of phenylacetic acid, p-hydroxyphenylacetic acid, p-aminophenylacetic acid, p-hydroxybenzoic acid, and ibuprofen in pure solvents. J Chem Eng Data. 2002;47(6):1379-83.
Hansen TB, Qu H. Formation of Piroxicam polymorphism in solution crystallization: Effect and interplay of operation parameters. Cryst Growth Des . 2015;15(9):4694-700.
Kim J-M, Chang S-M, Kim K-S, Chung M-K, Kim W-S. Acoustic influence on aggregation and agglomeration of crystals in reaction crystallization of cerium carbonate. Colloids Surfaces A Physicochem Eng Asp. 2011;375(1-3):193-9.
Kitamura M, Nakamura K. Effects of solvent composition and temperature on polymorphism and crystallization behavior of thiazole-derivative. J Cryst Growth. 2002;236(4):676-86.
Mallick S. Effect of solvent and polymer additives on crystallization. Indian J Pharm Sci. 2004;66(2):142.
Noubigh A, Oueslati MH. Measurement and modeling of the solubility of vanillin constituent of olive mill wastewater in binary water+ ethanol solvents mixtures between 278.15 K and 308.15 K, Aust. J Basic Appl Sci. 2014;8(9):396-403.
Patil S, Patil S, Navale S. Effect of Solvent and Crystallization Method on Physicochemical Properties of Aceclofenac and Fenofibrate. J Pharm Res Int. 2016;12(5):1-8.
Qing X-Y, Fu H-L, Shu G, Liu M-J, Zhou J-Y, Wu W-B, et al. Solubility and solution thermodynamics of diphenoxylate in different pure solvents. J Chem Eng Data . 2015;60(6):1629-33.
Raval MK, Patel JM, Parikh RK, Sheth NR. Dissolution enhancement of chlorzoxazone using cogrinding technique. Int J Pharm Investig. 2015;5(4):247.
Rohani S, Horne S, Murthy K. Control of product quality in batch crystallization of pharmaceuticals and fine chemicals. Part 1: Design of the crystallization process and the effect of solvent. Org Process Res Dev . 2005;9(6):858-72.
Stewart JT, Janicki CA. Chlorzoxazone. In: Analytical Profiles of Drug Substances. Elsevier. 1987. p. 119-44.
Vedantam S, Ranade VV. Crystallization: Key thermodynamic, kinetic and hydrodynamic aspects. Sadhana. 2013;38(6):1287-337.
Wang S, Song Z, Wang J, Dong Y, Wu M. Solubilities of ibuprofen in different pure solvents. J Chem Eng Data . 2010;55(11):5283-5.
Widenski DJ, Abbas A, Romagnoli JA. Comparison of different solubility equations for modeling in cooling crystallization. Chem Eng Process Process Intensif. 2010;49(12):1284-97.
Yurdakul S, Yurdakul M. FT-IR, FT-Raman spectra, and DFT computations of the vibrational spectra and molecular geometry of chlorzoxazone. Spectrochim Acta Part A Mol Biomol Spectrosc. 2014;126:339-48.
Zhang D, Xu S, Du S, Wang J, Gong J. Progress of pharmaceutical continuous crystallization. Engineering. 2017;3(3):354-364.
Zhang F, Tang Y, Wang L, Xu L, Liu G. Solubility determination and thermodynamic models for 2-methylnaphthalene in different solvents from T=(278.15 to 303.15) K. J Chem Eng Data . 2015;60(6):1699-705.
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