Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation
La solubilidad en equilibrio de la sulfadiazina (SD, 3) en mezclas de {acetonitrilo (MeCN, 1) + metanol (MeOH, 2)} a nueve temperaturas de 278,15 K a 318,15 K se ha determinado y correlacionado por medio de una correlación termodinámica bien conocida modelos. Se aplicaron cinco modelos, incluidos va...
- Autores:
-
Delgado, Daniel Ricardo
Bahamón-Hernandez, Otto
Enrique Cerquera, Nestor
Ortiz, Claudia Patricia
Martínez, Fleming
Rahimpour, Elaheh
Jouyban, Abolghasem
Acree Jr, William Eugene
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2021
- Institución:
- Universidad Cooperativa de Colombia
- Repositorio:
- Repositorio UCC
- Idioma:
- OAI Identifier:
- oai:repository.ucc.edu.co:20.500.12494/32872
- Acceso en línea:
- https://doi.org/10.1016/j.molliq.2020.114979
https://hdl.handle.net/20.500.12494/32872
- Palabra clave:
- Sulfadiazina
{acetonitrilo (1) + metanol (2)} mezclas
Cosolvencia
Termodinámica de disolución
Modelo Jouyban-Acree
Solvatación preferencial
IKBI
Sulfadiazine
{acetonitrile (1) + methanol (2)} mixtures
Cosolvency
Dissolution thermodynamics
Jouyban-Acree model
Preferential solvation
IKBI
- Rights
- embargoedAccess
- License
- Atribución – Sin Derivar
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dc.title.spa.fl_str_mv |
Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation |
title |
Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation |
spellingShingle |
Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation Sulfadiazina {acetonitrilo (1) + metanol (2)} mezclas Cosolvencia Termodinámica de disolución Modelo Jouyban-Acree Solvatación preferencial IKBI Sulfadiazine {acetonitrile (1) + methanol (2)} mixtures Cosolvency Dissolution thermodynamics Jouyban-Acree model Preferential solvation IKBI |
title_short |
Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation |
title_full |
Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation |
title_fullStr |
Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation |
title_full_unstemmed |
Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation |
title_sort |
Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation |
dc.creator.fl_str_mv |
Delgado, Daniel Ricardo Bahamón-Hernandez, Otto Enrique Cerquera, Nestor Ortiz, Claudia Patricia Martínez, Fleming Rahimpour, Elaheh Jouyban, Abolghasem Acree Jr, William Eugene |
dc.contributor.author.none.fl_str_mv |
Delgado, Daniel Ricardo Bahamón-Hernandez, Otto Enrique Cerquera, Nestor Ortiz, Claudia Patricia Martínez, Fleming Rahimpour, Elaheh Jouyban, Abolghasem Acree Jr, William Eugene |
dc.subject.spa.fl_str_mv |
Sulfadiazina {acetonitrilo (1) + metanol (2)} mezclas Cosolvencia Termodinámica de disolución Modelo Jouyban-Acree Solvatación preferencial IKBI |
topic |
Sulfadiazina {acetonitrilo (1) + metanol (2)} mezclas Cosolvencia Termodinámica de disolución Modelo Jouyban-Acree Solvatación preferencial IKBI Sulfadiazine {acetonitrile (1) + methanol (2)} mixtures Cosolvency Dissolution thermodynamics Jouyban-Acree model Preferential solvation IKBI |
dc.subject.other.spa.fl_str_mv |
Sulfadiazine {acetonitrile (1) + methanol (2)} mixtures Cosolvency Dissolution thermodynamics Jouyban-Acree model Preferential solvation IKBI |
description |
La solubilidad en equilibrio de la sulfadiazina (SD, 3) en mezclas de {acetonitrilo (MeCN, 1) + metanol (MeOH, 2)} a nueve temperaturas de 278,15 K a 318,15 K se ha determinado y correlacionado por medio de una correlación termodinámica bien conocida modelos. Se aplicaron cinco modelos, incluidos van't Hoff, la superficie de respuesta de mezcla (MRS), Jouyban-Acree, Jouyban-Acree-van't Hoff y los modelos de Wilson modificados al modelado matemático de datos de solubilidad. La precisión de cada modelo se investiga mediante las desviaciones relativas medias ( % MRD ) de la solubilidad retrocalculada. Todos los modelos usados muestran una MRD bajaValores de% (<8,0%) para los datos calculados que indican una buena correlación de los datos de solubilidad de sulfadiazina con los modelos matemáticos dados. Utilizando las ecuaciones de van't Hoff y Gibbs, se calcularon las respectivas cantidades termodinámicas aparentes de los procesos de disolución y mezcla, a saber, energía, entalpía y entropía de Gibbs. Se observó una relación de entalpía-entropía no lineal para SD en el gráfico de entalpía vs.Energía de Gibbs que exhibe pendiente negativa en la región de composición 0.00 < w 1 <0.05 indica un mecanismo de conducción de entropía para este proceso de transferencia, y pendientes variantes pero principalmente positivas el intervalo de composición 0,05 < w 1 <0,30, lo que indica el mecanismo impulsor de la entalpía para estos procesos de transferencia. Desde w1 = 0,30 para MeCN puro se observa una pendiente cercana a cero. Además, se analizó la solvatación preferencial de SD por MeCN o MeOH usando las integrales inversas de Kirkwood-Buff. Por tanto, SD se solvata preferentemente mediante moléculas de MeOH en mezclas ricas en MeOH. |
publishDate |
2021 |
dc.date.accessioned.none.fl_str_mv |
2021-01-27T15:48:29Z |
dc.date.available.none.fl_str_mv |
2021-01-27T15:48:29Z 2022-12-31 |
dc.date.issued.none.fl_str_mv |
2121-01-15 |
dc.type.none.fl_str_mv |
Artículo |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.coarversion.none.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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http://purl.org/coar/resource_type/c_6501 |
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publishedVersion |
dc.identifier.issn.spa.fl_str_mv |
01677322 |
dc.identifier.uri.spa.fl_str_mv |
https://doi.org/10.1016/j.molliq.2020.114979 |
dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/20.500.12494/32872 |
dc.identifier.bibliographicCitation.spa.fl_str_mv |
Delgado et al. Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation, Journal of Molecular Liquids Volume 322, 15 January 2021, 114979 |
identifier_str_mv |
01677322 Delgado et al. Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation, Journal of Molecular Liquids Volume 322, 15 January 2021, 114979 |
url |
https://doi.org/10.1016/j.molliq.2020.114979 https://hdl.handle.net/20.500.12494/32872 |
dc.relation.isversionof.spa.fl_str_mv |
https://bbibliograficas.ucc.edu.co:2152/science/article/pii/S0167732220372214 |
dc.relation.ispartofjournal.spa.fl_str_mv |
Journal of Molecular Liquids |
dc.relation.references.spa.fl_str_mv |
Y. Marcus On the preferential solvation of drugs and PAHs in binary solvent mixtures J. Mol. Liq., 140 (2008), pp. 61-67 Y. Marcus Preferential solvation of drugs in binary solvent mixtures Pharm. Anal. Acta, 8 (2017), p. 1000537 A. Jouyban Handbook of Solubility Data for Pharmaceuticals CRC Press, Boca Raton, FL (2010) A. Avdeef Absorption and Drug Development, Solubility, Permeability and Charge State Wiley-Interscience, Hoboken (NJ) (2003) Y. Marcus Solvent Mixtures: Properties and Selective Solvation Marcel Dekker, Inc., New York (NY) (2002) S. Budavari, M.J. O’Neil, A. Smith, P.E. Heckelman, J.R. Obenchain Jr., J.A.R. Gallipeau, M.A. D’Arecea The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals (13th ed.), Merck & Co., Inc., Whitehouse Station, NJ (2001) F. Martínez, A. Gómez Thermodynamics of partitioning of some sulfonamides in 1-octanol/buffer and liposome systems J. Phys. Org. Chem., 15 (2002), pp. 874-880 S. Gelone, J.A. O’Donell Anti-infectives A.R. Gennaro (Ed.), Remington: The Science and Practice of Pharmacy (21st ed.), Lippincott Williams & Wilkins, Philadelphia (PA) (2005) S.C. Sweetman (Ed.), Martindale: The Complete Drug Reference (36th ed.), Pharmaceutical Press, London (2009) F. Martínez, A. Gómez Thermodynamic study of the solubility of some sulfonamides in octanol, water, and the mutually saturated solvents J. Solut. Chem., 30 (2001), pp. 909-923 A. Romdhani, F. Martínez, O.A. Almanza, M.A. Peña, A. Jouyban, W.E. Acree Jr. Solubility of sulfacetamide in (ethanol + water) mixtures: Measurement, correlation, thermodynamics, preferential solvation and volumetric contribution at saturation J. Mol. Liq., 290 (2019), p. 111219 Y. Marcus The Properties of Solvents John Wiley & Sons, Chichester (UK) (1998) F. Tewes, F. Boury, J.P. Benoit Biodegradable microspheres: Advances in production technology S. Benita (Ed.), Microencapsulation: Methods and Industrial Applications (2nd ed.), Taylor & Francis, New York (NY) (2006), pp. 1-53 L.R. Greene, A.C. Blackburn, J.M. Miller Rapid, small-scale determination of organic solvent solubility using a thermogravimetric analyzer J. Pharm. Biomed. Anal., 39 (2005), pp. 344-347 Y. Kazakevich, R. Lobrutto HPLC for Pharmaceutical Scientists John Wiley & Sons, Inc., Hoboken (NJ) (2007) Y. Marcus The structure of and interactions in binary acetonitrile + water mixtures J. Phys. Org. Chem., 25 (2012), pp. 1072-1085 I. Cibulka, D. Nguyen, R. Holub Excess molar volumes of (an alkanol + acetonitrile) at 298.15 and 308.15 K J. Chem. Thermodyn., 16 (1984), pp. 159-164 I.R. Grguric, A.Z. Tasic, B.D. Djordjevic, M.L.J. Kijevcanin, S.P. Serbanovic Excess molar volume of the acetonitrile + alcohol systems at 298.15 K. Part I: Density measurements for acetonitrile + methanol, + ethanol systems J. Serb. Chem. Soc, 67 (2002), pp. 581-586 I. Nagata, K. Katoh, J. Koyaru Liquid-liquid equilibria for ternary systems containing acetonitrile Thermochim. Acta, 47 (1981), pp. 225-233 I. Nagata, K. Tamura Excess enthalpies of binary and ternary mixtures of acetonitrile with methanol, ethanol and benzene Fluid Phase Equilib., 24 (1985), pp. 289-306 A.P. Jogdand, P.L. Kadam Excess properties of acetonitrile + methanol binary mixtures at microwave frequency IOSR Journal of Engineering (IOSRJEN), 4 (3) (2014), pp. 47-55 A.K. Sum, S.I. Sandler, R. Bukowski, K. Szalewicz Prediction of the phase behavior of acetonitrile and methanol with ab initio pair potentials. II. The mixture J. Chem. Phys., 116 (2002), pp. 7637-7644 Y. Marcus Preferential solvation in mixed solvents. 15. Mixtures of acetonitrile with organic solvents J. Chem. Thermodyn., 135 (2019), pp. 55-59 Q. Zhang, Y. Yang, C. Cao, L. Cheng, Y. Shi, W. Yang, Y. Hua Thermodynamic models for determination of the solubility of dibenzothiophene in (methanol + acetonitrile) binary solvent mixtures J. Chem. Thermodyn., 80 (2015), pp. 7-12 P.H. Elworthy, E.C. Worthington The solubility of sulphadiazine in water–dimethylformamide mixtures J. Pharm. Pharmacol., 20 (1968), pp. 830-835 P. Bustamante, B. Escalera, A. Martin, E. Selles A modification of the extended Hildebrand approach to predict the solubility of structurally related drugs in solvent mixtures J. Pharm. Pharmacol., 45 (1993), pp. 253-257 D.R. Delgado, F. Martinez Solution thermodynamics of sulfadiazine in ethanol + water mixtures J. Mol. Liq., 187 (2013), pp. 99-105 D.R. Delgado, M.Á. Peña, F. Martínez Preferential solvation of some sulfonamides in 1,4–dioxane + water co–solvent mixtures at 298.15 K according to the inverse Kirkwood–Buff integrals method Rev. Acad. Colomb. Cienc., 38 (2014), pp. 104-114 D.R. Delgado, F. Martínez Preferential solvation of sulfadiazine, sulfamerazine and sulfamethazine in ethanol + water solvent mixtures according to the IKBI method J. Mol. Liq., 193 (2014), pp. 152-159 D.R. Delgado, F. Martínez Solubility and preferential solvation of sulfadiazine in methanol + water mixtures at several temperatures Fluid Phase Equilib., 379 (2014), pp. 128-138 D.R. Delgado, F. Martínez Solubility and solution thermodynamics of some sulfonamides in 1-propanol + water mixtures J. Solut. Chem., 43 (2014), pp. 836-852 D.R. Delgado, F. Martínez Preferential solvation of some structurally related sulfonamides in 1-propanol + water co-solvent mixtures Phys. Chem. Liq., 53 (2015), pp. 293-306 D.M. Jiménez, Z.J. Cárdenas, D.R. Delgado, M.Á. Peña, F. Martínez Solubility temperature dependence and preferential solvation of sulfadiazine in 1,4-dioxane + water co-solvent mixtures Fluid Phase Equilib., 397 (2015), pp. 26-36 M.M. Muñoz, D.R. Delgado, M.Á. Peña, A. Jouyban, F. Martínez Solubility and preferential solvation of sulfadiazine, sulfamerazine and sulfamethazine in propylene glycol + water mixtures at 298.15 K J. Mol. Liq., 204 (2015), pp. 132-136 D.M. Jiménez, Z.J. Cárdenas, F. Martínez Solubility and solution thermodynamics of sulfadiazine in polyethylene glycol 400 + water mixtures J. Mol. Liq., 216 (2016), pp. 239-245 D.R. Delgado, D.I. Caviedes-Rubio, C.P. Ortiz, Y.L. Parra-Pava, M.Á. Peña, A. Jouyban, S.N. Mirheydari, F. Martínez, W.E. Acree Jr. Solubility of sulphadiazine in (acetonitrile + water) mixtures: Measurement, correlation, thermodynamics and preferential solvation Phys. Chem. Liq., 58 (2020), pp. 381-396 J.T. Rubino Cosolvents and cosolvency J. Swarbrick, J.C. Boylan (Eds.), Encyclopedia of Pharmaceutical Technology, vol. 3, Marcel Dekker, Inc., New York (1988) S.H. Yalkowsky Solubility and Solubilization in Aqueous Media, American Chemical Society and Oxford University Press, New York (1999) A. Martin, P. Bustamante, A.H.C. Chun Physical Chemical Principles in the Pharmaceutical Sciences (4th ed.), Lea & Febiger, Philadelphia (1993) A.F.M. Barton Handbook of Solubility Parameters and Other Cohesion Parameters (2nd ed.), CRC Press, New York (1991) K.A. Connors Thermodynamics of Pharmaceutical Systems: An Introduction for Students of Pharmacy Wiley–Interscience, Hoboken, NJ (2002) R.F. Fedors A method for estimating both the solubility parameters and molar volumes of liquids Polym. Eng. Sci., 14 (1974), pp. 147-154 A. Kristl, G. Vesnaver Thermodynamic investigation of the effect of octanol–water mutual miscibility on the partitioning and solubility of some guanine derivatives J. Chem. Soc. Faraday Trans., 91 (1995), pp. 995-998 A. Jouyban, W.E. Acree Jr. Mathematical derivation of the Jouyban-Acree model to represent solute solubility data in mixed solvents at various temperatures J. Mol. Liq., 256 (2018), pp. 541-547 A. Jouyban Review of the cosolvency models for predicting solubility of drugs in water–cosolvent mixtures J. Pharm. Pharmaceut. Sci., 11 (2008), pp. 32-58 A. Jouyban Review of the cosolvency models for predicting drug solubility in solvent mixtures: An update J. Pharm. Pharmaceut. Sci., 22 (2019), pp. 466-485 R.R. Krug, W.G. Hunter, R.A. Grieger Enthalpy-entropy compensation. 1. Some fundamental statistical problems associated with the analysis of van’t Hoff and Arrhenius data J. Phys. Chem., 80 (1976), pp. 2335-2341 R.R. Krug, W.G. Hunter, R.A. Grieger Enthalpy-entropy compensation. 2. Separation of the chemical from the statistical effects J. Phys. Chem., 80 (1976), pp. 2341-2351 F. Shakeel, M. Iqbal, E. Ezzeldin, N. Haq Thermodynamics of solubility of ibrutinib in ethanol + water cosolvent mixtures at different temperatures J. Mol. Liq., 209 (2015), pp. 461-464 L. Wang, H. Zhang, Z. Shen, L. Xu, G. Liu Measurement and correlation of solubility of methyleneaminoacetonitrile in pure and binary solvents and thermodynamic properties of solution J. Chem. Thermodyn., 134 (2019), pp. 146-156 S. Alshehri, F. Shakeel Solubility determination, various solubility parameters and solution thermodynamics of sunitinib malate in some cosolvents, water and various (Transcutol + water) mixtures J. Mol. Liq., 307 (2020), p. 112970 G.L. Perlovich, S.V. Kurkov, A.N. Kinchin, A. Bauer-Brandl Thermodynamics of solutions III: comparison of the solvation of (+)-naproxen with other NSAIDs Eur. J. Pharm. Biopharm., 57 (2004), pp. 411-420 D.R. Delgado, O.A. Almanza, F. Martínez, M.A. Peña, A. Jouyban, W.E. Acree Jr. Solution thermodynamics and preferential solvation of sulfamethazine in (methanol + water) mixtures J. Chem. Thermodyn., 97 (2016), pp. 264-276 P. Bustamante, S. Romero, A. Reillo Thermodynamics of paracetamol in amphiprotic and amphiprotic—aprotic solvent mixtures Pharm. Pharmacol. Commun., 1 (1995), pp. 505-507 C. Bustamante, P. Bustamante Nonlinear enthalpy–entropy compensation for the solubility of phenacetin in dioxane–water solvent mixtures J. Pharm. Sci., 85 (1996), pp. 1109-1111 P. Bustamante, S. Romero, A. Peña, B. Escalera, A. Reillo Nonlinear enthalpy-entropy compensation for the solubility of drugs in solvent mixtures: paracetamol, acetanilide and nalidixic acid in dioxane-water J. Pharm. Sci., 87 (1998), pp. 1590-1596 Y. Marcus Preferential solvation in mixed solvents P.E. Smith, E. Matteoli, J.P. O’Connell (Eds.), Fluctuation Theory of Solutions: Applications in Chemistry, Chemical Engineering, and Biophysics, CRC Press, Taylor & Francis Group, Boca Raton (FL) (2013) W. Li, S. Qi, N. Wang, Z. Fei, A. Farajtabar, H. Zhao Solute-solvent and solvent-solvent interactions and preferential solvation of limonin in aqueous co-solvent mixtures of methanol and acetone J. Mol. Liq., 263 (2018), pp. 357-365 M. Zheng, A. Farajtabar, H. Zhao Solute-solvent and solvent-solvent interactions and preferential solvation of hesperidin in aqueous cosolvent mixtures of ethanol, isopropanol, propylene glycol and n-propanol J. Mol. Liq., 264 (2018), pp. 285-291 A. Ben-Naim Preferential solvation in two- and in three-component systems Pure Appl. Chem., 62 (1990), pp. 25-34 Y. Marcus Solubility and solvation in mixed solvent systems Pure Appl. Chem., 62 (1990), pp. 2069-2076 B.G. Alberding, B.J. Lear Concentration-dependent dynamics of hydrogen bonding between acetonitrile and methanol as determined by 1D vibrational spectroscopy J. Phys. Chem. A, 118 (2014), pp. 4363-4371 |
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Delgado, Daniel RicardoBahamón-Hernandez, OttoEnrique Cerquera, NestorOrtiz, Claudia PatriciaMartínez, FlemingRahimpour, ElahehJouyban, AbolghasemAcree Jr, William Eugene3222021-01-27T15:48:29Z2022-12-312021-01-27T15:48:29Z2121-01-1501677322https://doi.org/10.1016/j.molliq.2020.114979https://hdl.handle.net/20.500.12494/32872Delgado et al. Solubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation, Journal of Molecular Liquids Volume 322, 15 January 2021, 114979La solubilidad en equilibrio de la sulfadiazina (SD, 3) en mezclas de {acetonitrilo (MeCN, 1) + metanol (MeOH, 2)} a nueve temperaturas de 278,15 K a 318,15 K se ha determinado y correlacionado por medio de una correlación termodinámica bien conocida modelos. Se aplicaron cinco modelos, incluidos van't Hoff, la superficie de respuesta de mezcla (MRS), Jouyban-Acree, Jouyban-Acree-van't Hoff y los modelos de Wilson modificados al modelado matemático de datos de solubilidad. La precisión de cada modelo se investiga mediante las desviaciones relativas medias ( % MRD ) de la solubilidad retrocalculada. Todos los modelos usados muestran una MRD bajaValores de% (<8,0%) para los datos calculados que indican una buena correlación de los datos de solubilidad de sulfadiazina con los modelos matemáticos dados. Utilizando las ecuaciones de van't Hoff y Gibbs, se calcularon las respectivas cantidades termodinámicas aparentes de los procesos de disolución y mezcla, a saber, energía, entalpía y entropía de Gibbs. Se observó una relación de entalpía-entropía no lineal para SD en el gráfico de entalpía vs.Energía de Gibbs que exhibe pendiente negativa en la región de composición 0.00 < w 1 <0.05 indica un mecanismo de conducción de entropía para este proceso de transferencia, y pendientes variantes pero principalmente positivas el intervalo de composición 0,05 < w 1 <0,30, lo que indica el mecanismo impulsor de la entalpía para estos procesos de transferencia. Desde w1 = 0,30 para MeCN puro se observa una pendiente cercana a cero. Además, se analizó la solvatación preferencial de SD por MeCN o MeOH usando las integrales inversas de Kirkwood-Buff. Por tanto, SD se solvata preferentemente mediante moléculas de MeOH en mezclas ricas en MeOH.The equilibrium solubility of sulfadiazine (SD, 3) in {acetonitrile (MeCN, 1) + methanol (MeOH, 2)} mixtures at nine temperatures from 278.15 K to 318.15 K has been determined and correlated by means of some well-known thermodynamic correlation models. Five models including van't Hoff, the mixture response surface (MRS), Jouyban-Acree, Jouyban-Acree-van't Hoff and the modified Wilson models were applied to mathematical solubility data modelling. The accuracy of each model is investigated by the mean relative deviations (MRD%) of the back-calculated solubility. All used models show a low MRD% values (< 8.0%) for the calculated data indicating a good correlation of sulfadiazine solubility data with the given mathematical models. By using the van't Hoff and Gibbs equations the respective apparent thermodynamic quantities of the dissolution and mixing processes, namely Gibbs energy, enthalpy, and entropy, were calculated. Non-linear enthalpy–entropy relationship was observed for SD in the plot of enthalpy vs. Gibbs energy exhibiting negative slope in the composition region 0.00 < w1 < 0.05 indicating entropy-driving mechanism for this transfer process, and variant but mainly positive slopes in the composition interval 0.05 < w1 < 0.30, indicating enthalpy-driving mechanism for these transfer processes. From w1 = 0.30 to neat MeCN a slope near zero is observed. Furthermore, the preferential solvation of SD by MeCN or MeOH was analysed by using the inverse Kirkwood-Buff integrals. Thus, SD is preferentially solvated by MeOH molecules in MeOH-rich mixtures.Highlights. -- Abstract. -- Keywords. -- 1. Introduction. -- 2. Experimental section. -- 3. Results and discussion. -- 4. Conclusions. -- Declaration of Competing Interest. -- Acknowledgments. -- Appendix A. Supplementary data. -- References.http://scienti.colciencias.gov.co:8081/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001402116https://orcid.org/0000-0002-4835-9739https://scienti.minciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000004151danielr.delgado@campusucc.edu.cohttps://scholar.google.es/citations?user=OW0mejcAAAAJ&hl=es10Elsevier B.V.Universidad Cooperativa de Colombia, Facultad de Ingenierías, Ingeniería Industrial, NeivaIngeniería IndustrialNeivahttps://bbibliograficas.ucc.edu.co:2152/science/article/pii/S0167732220372214Journal of Molecular LiquidsY. Marcus On the preferential solvation of drugs and PAHs in binary solvent mixtures J. Mol. Liq., 140 (2008), pp. 61-67Y. Marcus Preferential solvation of drugs in binary solvent mixtures Pharm. Anal. Acta, 8 (2017), p. 1000537A. Jouyban Handbook of Solubility Data for Pharmaceuticals CRC Press, Boca Raton, FL (2010)A. Avdeef Absorption and Drug Development, Solubility, Permeability and Charge State Wiley-Interscience, Hoboken (NJ) (2003)Y. Marcus Solvent Mixtures: Properties and Selective Solvation Marcel Dekker, Inc., New York (NY) (2002)S. Budavari, M.J. O’Neil, A. Smith, P.E. Heckelman, J.R. Obenchain Jr., J.A.R. Gallipeau, M.A. D’Arecea The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals (13th ed.), Merck & Co., Inc., Whitehouse Station, NJ (2001)F. Martínez, A. Gómez Thermodynamics of partitioning of some sulfonamides in 1-octanol/buffer and liposome systems J. Phys. Org. Chem., 15 (2002), pp. 874-880S. Gelone, J.A. O’Donell Anti-infectives A.R. Gennaro (Ed.), Remington: The Science and Practice of Pharmacy (21st ed.), Lippincott Williams & Wilkins, Philadelphia (PA) (2005)S.C. Sweetman (Ed.), Martindale: The Complete Drug Reference (36th ed.), Pharmaceutical Press, London (2009)F. Martínez, A. Gómez Thermodynamic study of the solubility of some sulfonamides in octanol, water, and the mutually saturated solvents J. Solut. Chem., 30 (2001), pp. 909-923A. Romdhani, F. Martínez, O.A. Almanza, M.A. Peña, A. Jouyban, W.E. Acree Jr. Solubility of sulfacetamide in (ethanol + water) mixtures: Measurement, correlation, thermodynamics, preferential solvation and volumetric contribution at saturation J. Mol. Liq., 290 (2019), p. 111219Y. Marcus The Properties of Solvents John Wiley & Sons, Chichester (UK) (1998)F. Tewes, F. Boury, J.P. Benoit Biodegradable microspheres: Advances in production technology S. Benita (Ed.), Microencapsulation: Methods and Industrial Applications (2nd ed.), Taylor & Francis, New York (NY) (2006), pp. 1-53L.R. Greene, A.C. Blackburn, J.M. Miller Rapid, small-scale determination of organic solvent solubility using a thermogravimetric analyzer J. Pharm. Biomed. Anal., 39 (2005), pp. 344-347Y. Kazakevich, R. Lobrutto HPLC for Pharmaceutical Scientists John Wiley & Sons, Inc., Hoboken (NJ) (2007)Y. Marcus The structure of and interactions in binary acetonitrile + water mixtures J. Phys. Org. Chem., 25 (2012), pp. 1072-1085I. Cibulka, D. Nguyen, R. Holub Excess molar volumes of (an alkanol + acetonitrile) at 298.15 and 308.15 K J. Chem. Thermodyn., 16 (1984), pp. 159-164I.R. Grguric, A.Z. Tasic, B.D. Djordjevic, M.L.J. Kijevcanin, S.P. Serbanovic Excess molar volume of the acetonitrile + alcohol systems at 298.15 K. Part I: Density measurements for acetonitrile + methanol, + ethanol systems J. Serb. Chem. Soc, 67 (2002), pp. 581-586I. Nagata, K. Katoh, J. Koyaru Liquid-liquid equilibria for ternary systems containing acetonitrile Thermochim. Acta, 47 (1981), pp. 225-233I. Nagata, K. Tamura Excess enthalpies of binary and ternary mixtures of acetonitrile with methanol, ethanol and benzene Fluid Phase Equilib., 24 (1985), pp. 289-306A.P. Jogdand, P.L. Kadam Excess properties of acetonitrile + methanol binary mixtures at microwave frequency IOSR Journal of Engineering (IOSRJEN), 4 (3) (2014), pp. 47-55A.K. Sum, S.I. Sandler, R. Bukowski, K. Szalewicz Prediction of the phase behavior of acetonitrile and methanol with ab initio pair potentials. II. The mixture J. Chem. Phys., 116 (2002), pp. 7637-7644Y. Marcus Preferential solvation in mixed solvents. 15. Mixtures of acetonitrile with organic solvents J. Chem. Thermodyn., 135 (2019), pp. 55-59Q. Zhang, Y. Yang, C. Cao, L. Cheng, Y. Shi, W. Yang, Y. Hua Thermodynamic models for determination of the solubility of dibenzothiophene in (methanol + acetonitrile) binary solvent mixtures J. Chem. Thermodyn., 80 (2015), pp. 7-12P.H. Elworthy, E.C. Worthington The solubility of sulphadiazine in water–dimethylformamide mixtures J. Pharm. Pharmacol., 20 (1968), pp. 830-835P. Bustamante, B. Escalera, A. Martin, E. Selles A modification of the extended Hildebrand approach to predict the solubility of structurally related drugs in solvent mixtures J. Pharm. Pharmacol., 45 (1993), pp. 253-257D.R. Delgado, F. Martinez Solution thermodynamics of sulfadiazine in ethanol + water mixtures J. Mol. Liq., 187 (2013), pp. 99-105D.R. Delgado, M.Á. Peña, F. Martínez Preferential solvation of some sulfonamides in 1,4–dioxane + water co–solvent mixtures at 298.15 K according to the inverse Kirkwood–Buff integrals method Rev. Acad. Colomb. Cienc., 38 (2014), pp. 104-114D.R. Delgado, F. Martínez Preferential solvation of sulfadiazine, sulfamerazine and sulfamethazine in ethanol + water solvent mixtures according to the IKBI method J. Mol. Liq., 193 (2014), pp. 152-159D.R. Delgado, F. Martínez Solubility and preferential solvation of sulfadiazine in methanol + water mixtures at several temperatures Fluid Phase Equilib., 379 (2014), pp. 128-138D.R. Delgado, F. Martínez Solubility and solution thermodynamics of some sulfonamides in 1-propanol + water mixtures J. Solut. Chem., 43 (2014), pp. 836-852D.R. Delgado, F. Martínez Preferential solvation of some structurally related sulfonamides in 1-propanol + water co-solvent mixtures Phys. Chem. Liq., 53 (2015), pp. 293-306D.M. Jiménez, Z.J. Cárdenas, D.R. Delgado, M.Á. Peña, F. Martínez Solubility temperature dependence and preferential solvation of sulfadiazine in 1,4-dioxane + water co-solvent mixtures Fluid Phase Equilib., 397 (2015), pp. 26-36M.M. Muñoz, D.R. Delgado, M.Á. Peña, A. Jouyban, F. Martínez Solubility and preferential solvation of sulfadiazine, sulfamerazine and sulfamethazine in propylene glycol + water mixtures at 298.15 K J. Mol. Liq., 204 (2015), pp. 132-136D.M. Jiménez, Z.J. Cárdenas, F. Martínez Solubility and solution thermodynamics of sulfadiazine in polyethylene glycol 400 + water mixtures J. Mol. Liq., 216 (2016), pp. 239-245D.R. Delgado, D.I. Caviedes-Rubio, C.P. Ortiz, Y.L. Parra-Pava, M.Á. Peña, A. Jouyban, S.N. Mirheydari, F. Martínez, W.E. Acree Jr. Solubility of sulphadiazine in (acetonitrile + water) mixtures: Measurement, correlation, thermodynamics and preferential solvation Phys. Chem. Liq., 58 (2020), pp. 381-396J.T. Rubino Cosolvents and cosolvency J. Swarbrick, J.C. Boylan (Eds.), Encyclopedia of Pharmaceutical Technology, vol. 3, Marcel Dekker, Inc., New York (1988)S.H. Yalkowsky Solubility and Solubilization in Aqueous Media, American Chemical Society and Oxford University Press, New York (1999)A. Martin, P. Bustamante, A.H.C. Chun Physical Chemical Principles in the Pharmaceutical Sciences (4th ed.), Lea & Febiger, Philadelphia (1993)A.F.M. Barton Handbook of Solubility Parameters and Other Cohesion Parameters (2nd ed.), CRC Press, New York (1991)K.A. Connors Thermodynamics of Pharmaceutical Systems: An Introduction for Students of Pharmacy Wiley–Interscience, Hoboken, NJ (2002)R.F. Fedors A method for estimating both the solubility parameters and molar volumes of liquids Polym. Eng. Sci., 14 (1974), pp. 147-154A. Kristl, G. Vesnaver Thermodynamic investigation of the effect of octanol–water mutual miscibility on the partitioning and solubility of some guanine derivatives J. Chem. Soc. Faraday Trans., 91 (1995), pp. 995-998A. Jouyban, W.E. Acree Jr. Mathematical derivation of the Jouyban-Acree model to represent solute solubility data in mixed solvents at various temperatures J. Mol. Liq., 256 (2018), pp. 541-547A. Jouyban Review of the cosolvency models for predicting solubility of drugs in water–cosolvent mixtures J. Pharm. Pharmaceut. Sci., 11 (2008), pp. 32-58A. Jouyban Review of the cosolvency models for predicting drug solubility in solvent mixtures: An update J. Pharm. Pharmaceut. Sci., 22 (2019), pp. 466-485R.R. Krug, W.G. Hunter, R.A. Grieger Enthalpy-entropy compensation. 1. Some fundamental statistical problems associated with the analysis of van’t Hoff and Arrhenius data J. Phys. Chem., 80 (1976), pp. 2335-2341R.R. Krug, W.G. Hunter, R.A. Grieger Enthalpy-entropy compensation. 2. Separation of the chemical from the statistical effects J. Phys. Chem., 80 (1976), pp. 2341-2351F. Shakeel, M. Iqbal, E. Ezzeldin, N. Haq Thermodynamics of solubility of ibrutinib in ethanol + water cosolvent mixtures at different temperatures J. Mol. Liq., 209 (2015), pp. 461-464L. Wang, H. Zhang, Z. Shen, L. Xu, G. Liu Measurement and correlation of solubility of methyleneaminoacetonitrile in pure and binary solvents and thermodynamic properties of solution J. Chem. Thermodyn., 134 (2019), pp. 146-156S. Alshehri, F. Shakeel Solubility determination, various solubility parameters and solution thermodynamics of sunitinib malate in some cosolvents, water and various (Transcutol + water) mixtures J. Mol. Liq., 307 (2020), p. 112970G.L. Perlovich, S.V. Kurkov, A.N. Kinchin, A. Bauer-Brandl Thermodynamics of solutions III: comparison of the solvation of (+)-naproxen with other NSAIDs Eur. J. Pharm. Biopharm., 57 (2004), pp. 411-420D.R. Delgado, O.A. Almanza, F. Martínez, M.A. Peña, A. Jouyban, W.E. Acree Jr. Solution thermodynamics and preferential solvation of sulfamethazine in (methanol + water) mixtures J. Chem. Thermodyn., 97 (2016), pp. 264-276P. Bustamante, S. Romero, A. Reillo Thermodynamics of paracetamol in amphiprotic and amphiprotic—aprotic solvent mixtures Pharm. Pharmacol. Commun., 1 (1995), pp. 505-507C. Bustamante, P. Bustamante Nonlinear enthalpy–entropy compensation for the solubility of phenacetin in dioxane–water solvent mixtures J. Pharm. Sci., 85 (1996), pp. 1109-1111P. Bustamante, S. Romero, A. Peña, B. Escalera, A. Reillo Nonlinear enthalpy-entropy compensation for the solubility of drugs in solvent mixtures: paracetamol, acetanilide and nalidixic acid in dioxane-water J. Pharm. Sci., 87 (1998), pp. 1590-1596Y. Marcus Preferential solvation in mixed solvents P.E. Smith, E. Matteoli, J.P. O’Connell (Eds.), Fluctuation Theory of Solutions: Applications in Chemistry, Chemical Engineering, and Biophysics, CRC Press, Taylor & Francis Group, Boca Raton (FL) (2013)W. Li, S. Qi, N. Wang, Z. Fei, A. Farajtabar, H. Zhao Solute-solvent and solvent-solvent interactions and preferential solvation of limonin in aqueous co-solvent mixtures of methanol and acetone J. Mol. Liq., 263 (2018), pp. 357-365M. Zheng, A. Farajtabar, H. Zhao Solute-solvent and solvent-solvent interactions and preferential solvation of hesperidin in aqueous cosolvent mixtures of ethanol, isopropanol, propylene glycol and n-propanol J. Mol. Liq., 264 (2018), pp. 285-291A. Ben-Naim Preferential solvation in two- and in three-component systems Pure Appl. Chem., 62 (1990), pp. 25-34Y. Marcus Solubility and solvation in mixed solvent systems Pure Appl. Chem., 62 (1990), pp. 2069-2076B.G. Alberding, B.J. Lear Concentration-dependent dynamics of hydrogen bonding between acetonitrile and methanol as determined by 1D vibrational spectroscopy J. Phys. Chem. A, 118 (2014), pp. 4363-4371Sulfadiazina{acetonitrilo (1) + metanol (2)} mezclasCosolvenciaTermodinámica de disoluciónModelo Jouyban-AcreeSolvatación preferencialIKBISulfadiazine{acetonitrile (1) + methanol (2)} mixturesCosolvencyDissolution thermodynamicsJouyban-Acree modelPreferential solvationIKBISolubility of sulfadiazine in (acetonitrile + methanol) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvationArtículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAtribución – Sin Derivarinfo:eu-repo/semantics/embargoedAccesshttp://purl.org/coar/access_right/c_f1cfPublicationLICENSElicense.txtlicense.txttext/plain; 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