Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures

Los estudios termodinámicos de solubilidad de medicamentos en mezclas cosolventes a diferentes temperaturas generan información de gran importancia para las ciencias farmacéuticas, médicas y ambientales. El objetivo de esta investigación es analizar termodinámicamente la solubilidad de la progestero...

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Autores:
Torres-Cardozo, Andrea
Delgado, Daniel
Cerquera, Nestor
Ortiz, Claudia
Osorio-Gallego, Jhonny
Cardenas-Torres, Rossember Edén
Angarita-Reina, Fredy
Martinez, Fleming
Delgado, Daniel Ricardo
Tipo de recurso:
Article of journal
Fecha de publicación:
2022
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
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OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/46627
Acceso en línea:
https://hdl.handle.net/20.500.12494/46627
Palabra clave:
Progesterona
Mezcla de cosolventes
Termodinámica de Soluciones
Modelos de solubilidad
Q1
Progesterone
Cosolvent mixtures
Thermodynamic solutions
Solubility model
Rights
openAccess
License
Atribución – Sin Derivar
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oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/46627
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures
title Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures
spellingShingle Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures
Progesterona
Mezcla de cosolventes
Termodinámica de Soluciones
Modelos de solubilidad
Q1
Progesterone
Cosolvent mixtures
Thermodynamic solutions
Solubility model
title_short Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures
title_full Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures
title_fullStr Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures
title_full_unstemmed Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures
title_sort Thermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperatures
dc.creator.fl_str_mv Torres-Cardozo, Andrea
Delgado, Daniel
Cerquera, Nestor
Ortiz, Claudia
Osorio-Gallego, Jhonny
Cardenas-Torres, Rossember Edén
Angarita-Reina, Fredy
Martinez, Fleming
Delgado, Daniel Ricardo
dc.contributor.advisor.none.fl_str_mv Delgado, Daniel Ricardo
dc.contributor.author.none.fl_str_mv Torres-Cardozo, Andrea
Delgado, Daniel
Cerquera, Nestor
Ortiz, Claudia
Osorio-Gallego, Jhonny
Cardenas-Torres, Rossember Edén
Angarita-Reina, Fredy
Martinez, Fleming
Delgado, Daniel Ricardo
dc.subject.spa.fl_str_mv Progesterona
Mezcla de cosolventes
Termodinámica de Soluciones
Modelos de solubilidad
topic Progesterona
Mezcla de cosolventes
Termodinámica de Soluciones
Modelos de solubilidad
Q1
Progesterone
Cosolvent mixtures
Thermodynamic solutions
Solubility model
dc.subject.classification.spa.fl_str_mv Q1
dc.subject.other.spa.fl_str_mv Progesterone
Cosolvent mixtures
Thermodynamic solutions
Solubility model
description Los estudios termodinámicos de solubilidad de medicamentos en mezclas cosolventes a diferentes temperaturas generan información de gran importancia para las ciencias farmacéuticas, médicas y ambientales. El objetivo de esta investigación es analizar termodinámicamente la solubilidad de la progesterona (PG) en mezclas cosolventes {1-octanol (1) + etanol (2)} de 278,15 K a 318,15 K (nueve temperaturas de estudio). La solubilidad de la progesterona (en fracción mol) aumentó con la adición de 1-octanol a la mezcla de cosolvente, presentando su valor más bajo (3,474 ± 0,03 × 10-3) en etanol puro (EtOH) a 278,15 K y su valor más alto (132,4 ± 3,0 × 10-3) en 1-octanol puro ( El proceso de solución de la progesterona es endotérmico y es impulsado por la entalpía de la solución. En cuanto a la termodinámica de la mezcla, el aumento de la concentración de 1-octanol favorece la formación de la cavidad y, por lo tanto, el aumento de la solubilidad de la progesterona. Según el análisis de compensación de entalpía entropía (EEC), se corrobora que el proceso de solución está impulsado por la entalpía. Finalmente, se evaluaron siete modelos (Apelblat, λh, Yaws, NRTL, Wilson y Wilson modificado), que presentaron un MRD% menos de 1,0, lo que demostró una buena correlación entre los datos obtenidos con cada uno de los modelos y los datos obtenidos experimentalmente.
publishDate 2022
dc.date.accessioned.none.fl_str_mv 2022-10-06T15:42:02Z
dc.date.available.none.fl_str_mv 2022-10-06T15:42:02Z
dc.date.issued.none.fl_str_mv 2022-09-06
dc.type.none.fl_str_mv Artículo
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dc.identifier.issn.spa.fl_str_mv 1110-0168
dc.identifier.uri.spa.fl_str_mv 10.1016/j.aej.2022.08.035
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/46627
dc.identifier.bibliographicCitation.spa.fl_str_mv Andrea Torres-Cardozo, Nestor Enrique Cerquera, Claudia Patricia Ortiz, Jhonny Osorio-Gallego, Rossember Edén Cardenas-Torres, Fredy Angarita-Reina, Fleming Martinez, Daniel Ricardo Delgado, Thermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures, Alexandria Engineering Journal, 2022.
identifier_str_mv 1110-0168
10.1016/j.aej.2022.08.035
Andrea Torres-Cardozo, Nestor Enrique Cerquera, Claudia Patricia Ortiz, Jhonny Osorio-Gallego, Rossember Edén Cardenas-Torres, Fredy Angarita-Reina, Fleming Martinez, Daniel Ricardo Delgado, Thermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures, Alexandria Engineering Journal, 2022.
url https://hdl.handle.net/20.500.12494/46627
dc.relation.ispartofseries.spa.fl_str_mv Alexandria Engineering Journal
dc.relation.isversionof.spa.fl_str_mv https://www.sciencedirect.com/science/article/pii/S1110016822005671
dc.relation.ispartofjournal.spa.fl_str_mv Alexandria Engineering Journal
dc.relation.references.spa.fl_str_mv H. Kuhl Pharmacology of estrogens and progestogens: influence of different routes of administration Climacteric., 8 (Suppl 1) (2005), pp. 3-63, 10.1080/13697130500148875
X. Ruan, A.O. Mueck Systemic progesterone therapy—Oral, vaginal, injections and even transdermal? Maturitas., 79 (2014), pp. 248-255, 10.1016/J.MATURITAS.2014.07.009
X. Ruan, A.O. Mueck Systemic progesterone therapy—Oral, vaginal, injections and even transdermal? Maturitas., 79 (2014), pp. 248-255, 10.1016/J.MATURITAS.2014.07.009
W. Ciampaglia, G.E. Cognigni Clinical use of progesterone in infertility and assisted reproduction Acta Obstet. Gynecol. Scand., 94 (2015), pp. 17-27, 10.1111/AOGS.12770
M. Filicori Clinical roles and applications of progesterone in reproductive medicine: an overview Acta Obstet. Gynecol. Scand., 94 (2015), pp. 3-7, 10.1111/AOGS.12791
S. Prakongpan, T. Nagai Solubility of acetaminophen in cosolvents Chem. Pharm. Bull., 32 (1984), pp. 340-343, 10.1248/CPB.32.340
D.R. Delgado, Latex-Molecular-Structures, (2022). https://github.com/drdelgad0/Latex-Molecular-Structures (accessed April 12, 2022).
A.N. Martin, Pilar. Bustamante, A.H.C. Chun, Physical Pharmacy: Physical Chemical Principles in the Pharmaceutical Sciences, 4th ed., Lippincott Williams & Wilking, Philadelphia, 1993.
H. Ideguchi, Y. Takasaki, S. Kondo, M. Nakanose, N. Teradahira, Y. Yamamoto, U. Mouri, H. Nakahara Solubilization of progesterone and its derivatives into gemini surfactant solutions J. Oleo Sci., 69 (2020), pp. 557-562, 10.5650/JOS.ESS20007
S.H. Yalkowsky Solubility and solubilization in aqueous media American Chemical Society, New York (1999)
A. Jouyban Handbook of solubility data for pharmaceuticals CRC Press, Boca Raton (FL), FL (2010)
F. Liu, H. Zhao, A. Farajtabar, P. Zhu, A. Jouyban, W.E. Acree Quantitative surface analysis of paclobutrazol molecule and comprehensive insight into its solubility in aqueous co-solvent solutions The Journal of Chemical Thermodynamics., 170 (2022), Article 106787, 10.1016/J.JCT.2022.106787
Y. Cong, C. Du, K. Xing, Y. Bian, X. Li, M. Wang Research on dissolution of actarit in aqueous mixtures: Solubility determination and correlation, preferential solvation, solvent effect and thermodynamics Journal of Molecular Liquids., 358 (2022), Article 119141, 10.1016/J.MOLLIQ.2022.119141
H. Rezaei, E. Rahimpour, H. Zhao, F. Martinez, M. Barzegar-Jalali, A. Jouyban Solubility of baclofen in some neat and mixed solvents at different temperatures Journal of Molecular Liquids., 347 (2022), Article 118352, 10.1016/J.MOLLIQ.2021.118352
A. Jouyban Review of the Cosolvency Models for Predicting Drug Solubility in Solvent Mixtures: An Update Journal of Pharmacy & Pharmaceutical Sciences., 22 (2019), pp. 466-485 https://doi.org/10.18433/JPPS30611
E. Mohammadian, A. Foroumadi, Z. Hasanvand, E. Rahimpour, H. Zhao, A. Jouyban Simulation of mesalazine solubility in the binary solvents at various temperatures Journal of Molecular Liquids., 357 (2022), Article 119160, 10.1016/J.MOLLIQ.2022.119160
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dc.publisher.spa.fl_str_mv Elsevier
Universidad Cooperativa de Colombia, Facultad de Ingenierías, Ingeniería Civil, Neiva
dc.publisher.program.spa.fl_str_mv Ingeniería Civil
dc.publisher.place.spa.fl_str_mv Neiva
institution Universidad Cooperativa de Colombia
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spelling Delgado, Daniel RicardoTorres-Cardozo, AndreaDelgado, DanielCerquera, NestorOrtiz, ClaudiaOsorio-Gallego, JhonnyCardenas-Torres, Rossember EdénAngarita-Reina, FredyMartinez, FlemingDelgado, Daniel Ricardo12022-10-06T15:42:02Z2022-10-06T15:42:02Z2022-09-061110-016810.1016/j.aej.2022.08.035https://hdl.handle.net/20.500.12494/46627Andrea Torres-Cardozo, Nestor Enrique Cerquera, Claudia Patricia Ortiz, Jhonny Osorio-Gallego, Rossember Edén Cardenas-Torres, Fredy Angarita-Reina, Fleming Martinez, Daniel Ricardo Delgado, Thermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures, Alexandria Engineering Journal, 2022.Los estudios termodinámicos de solubilidad de medicamentos en mezclas cosolventes a diferentes temperaturas generan información de gran importancia para las ciencias farmacéuticas, médicas y ambientales. El objetivo de esta investigación es analizar termodinámicamente la solubilidad de la progesterona (PG) en mezclas cosolventes {1-octanol (1) + etanol (2)} de 278,15 K a 318,15 K (nueve temperaturas de estudio). La solubilidad de la progesterona (en fracción mol) aumentó con la adición de 1-octanol a la mezcla de cosolvente, presentando su valor más bajo (3,474 ± 0,03 × 10-3) en etanol puro (EtOH) a 278,15 K y su valor más alto (132,4 ± 3,0 × 10-3) en 1-octanol puro ( El proceso de solución de la progesterona es endotérmico y es impulsado por la entalpía de la solución. En cuanto a la termodinámica de la mezcla, el aumento de la concentración de 1-octanol favorece la formación de la cavidad y, por lo tanto, el aumento de la solubilidad de la progesterona. Según el análisis de compensación de entalpía entropía (EEC), se corrobora que el proceso de solución está impulsado por la entalpía. Finalmente, se evaluaron siete modelos (Apelblat, λh, Yaws, NRTL, Wilson y Wilson modificado), que presentaron un MRD% menos de 1,0, lo que demostró una buena correlación entre los datos obtenidos con cada uno de los modelos y los datos obtenidos experimentalmente.Thermodynamic studies of drug solubility in cosolvent mixtures at different temperatures generate information of great importance for pharmaceutical, medical, and environmental sciences. The objective of this research is to thermodynamically analyze the solubility of progesterone (PG) in cosolvent mixtures {1-octanol (1) + ethanol (2)} from 278.15 K to 318.15 K (nine study temperatures). The solubility of progesterone (in mole fraction) increased with the addition of 1-octanol to the cosolvent mixture, presenting its lowest value (3.474 ± 0.03 × 10-3) in pure ethanol (EtOH) at 278.15 K and its highest value (132.4 ± 3.0 × 10-3) in pure 1-octanol (OCT) at 318.15 K. The solution process of progesterone is endothermic and is driven by the enthalpy of solution. Regarding the thermodynamics of the mixture, the increase in the 1-octanol concentration favors the formation of the cavity and therefore the increase in the solubility of the progesterone. According to the entropic enthalpy compensation (EEC) analysis, it is corroborated that the solution process is driven by enthalpy. Finally, seven models (Apelblat, λh, Yaws, NRTL, Wilson and modified Wilson) were evaluated, which presented MRD% less than 1.0, which demonstrated a good correlation between the data obtained with each of the models and the data obtained experimentally.1. Introduction, 2. Materials and methods, 3. Resultado, 4. Conclusiones, 5. Bibliografíahttps://scienti.minciencias.gov.co/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.com/citations?user=OW0mejcAAAAJ&hl=es17ElsevierUniversidad Cooperativa de Colombia, Facultad de Ingenierías, Ingeniería Civil, NeivaIngeniería CivilNeivaAlexandria Engineering Journalhttps://www.sciencedirect.com/science/article/pii/S1110016822005671Alexandria Engineering JournalH. Kuhl Pharmacology of estrogens and progestogens: influence of different routes of administration Climacteric., 8 (Suppl 1) (2005), pp. 3-63, 10.1080/13697130500148875X. Ruan, A.O. Mueck Systemic progesterone therapy—Oral, vaginal, injections and even transdermal? Maturitas., 79 (2014), pp. 248-255, 10.1016/J.MATURITAS.2014.07.009X. Ruan, A.O. Mueck Systemic progesterone therapy—Oral, vaginal, injections and even transdermal? Maturitas., 79 (2014), pp. 248-255, 10.1016/J.MATURITAS.2014.07.009W. Ciampaglia, G.E. Cognigni Clinical use of progesterone in infertility and assisted reproduction Acta Obstet. Gynecol. Scand., 94 (2015), pp. 17-27, 10.1111/AOGS.12770M. Filicori Clinical roles and applications of progesterone in reproductive medicine: an overview Acta Obstet. Gynecol. Scand., 94 (2015), pp. 3-7, 10.1111/AOGS.12791S. Prakongpan, T. Nagai Solubility of acetaminophen in cosolvents Chem. Pharm. Bull., 32 (1984), pp. 340-343, 10.1248/CPB.32.340D.R. Delgado, Latex-Molecular-Structures, (2022). https://github.com/drdelgad0/Latex-Molecular-Structures (accessed April 12, 2022).A.N. Martin, Pilar. Bustamante, A.H.C. Chun, Physical Pharmacy: Physical Chemical Principles in the Pharmaceutical Sciences, 4th ed., Lippincott Williams & Wilking, Philadelphia, 1993.H. Ideguchi, Y. Takasaki, S. Kondo, M. Nakanose, N. Teradahira, Y. Yamamoto, U. Mouri, H. Nakahara Solubilization of progesterone and its derivatives into gemini surfactant solutions J. Oleo Sci., 69 (2020), pp. 557-562, 10.5650/JOS.ESS20007S.H. Yalkowsky Solubility and solubilization in aqueous media American Chemical Society, New York (1999)A. Jouyban Handbook of solubility data for pharmaceuticals CRC Press, Boca Raton (FL), FL (2010)F. Liu, H. Zhao, A. Farajtabar, P. Zhu, A. Jouyban, W.E. Acree Quantitative surface analysis of paclobutrazol molecule and comprehensive insight into its solubility in aqueous co-solvent solutions The Journal of Chemical Thermodynamics., 170 (2022), Article 106787, 10.1016/J.JCT.2022.106787Y. Cong, C. Du, K. Xing, Y. Bian, X. Li, M. Wang Research on dissolution of actarit in aqueous mixtures: Solubility determination and correlation, preferential solvation, solvent effect and thermodynamics Journal of Molecular Liquids., 358 (2022), Article 119141, 10.1016/J.MOLLIQ.2022.119141H. Rezaei, E. Rahimpour, H. Zhao, F. Martinez, M. Barzegar-Jalali, A. Jouyban Solubility of baclofen in some neat and mixed solvents at different temperatures Journal of Molecular Liquids., 347 (2022), Article 118352, 10.1016/J.MOLLIQ.2021.118352A. Jouyban Review of the Cosolvency Models for Predicting Drug Solubility in Solvent Mixtures: An Update Journal of Pharmacy & Pharmaceutical Sciences., 22 (2019), pp. 466-485 https://doi.org/10.18433/JPPS30611E. Mohammadian, A. Foroumadi, Z. Hasanvand, E. Rahimpour, H. Zhao, A. Jouyban Simulation of mesalazine solubility in the binary solvents at various temperatures Journal of Molecular Liquids., 357 (2022), Article 119160, 10.1016/J.MOLLIQ.2022.119160ProgesteronaMezcla de cosolventesTermodinámica de SolucionesModelos de solubilidadQ1ProgesteroneCosolvent mixturesThermodynamic solutionsSolubility modelThermodynamic analysis of the solubility of progesterone in 1-octanol+ ethanol cosolvent mixtures at different temperaturesArtículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionAtribución – Sin Derivarinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationORIGINALThermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures.pdfThermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures.pdfCopia Artículoapplication/pdf1113849https://repository.ucc.edu.co/bitstreams/2de1a938-5721-4ab4-ad12-6a0466b89872/downloadc38900e787180fb347b65c635338d038MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repository.ucc.edu.co/bitstreams/7b3f79b6-e846-443e-bc1c-8388e2e1737d/download8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILThermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures.pdf.jpgThermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures.pdf.jpgGenerated Thumbnailimage/jpeg5990https://repository.ucc.edu.co/bitstreams/37c80c17-d30e-4f10-87e4-d0b430c5d713/downloadd1027e044374de89f343c528ed948df8MD53TEXTThermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures.pdf.txtThermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures.pdf.txtExtracted texttext/plain77957https://repository.ucc.edu.co/bitstreams/4b9f5ec0-1c02-4623-b5cd-f495ae432db3/downloadfc79473b52c2b4980b691915ebd38c22MD5420.500.12494/46627oai:repository.ucc.edu.co:20.500.12494/466272024-08-20 16:15:56.544open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.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