Diseño de sistemas orodispersables a base de colágeno tipo I

Contexto: Se propone el uso de colágeno tipo I en lugar de desintegrantes sintéticos comunes como crospovidona y croscarmelosa sódica, ofreciendo una alternativa natural con características hidrófilas, propiedades de hinchamiento en agua similares, que ofrece una excelente biocompatibilidad a un cos...

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Autores:
Rodriguez Ramirez, Valentina
Roncancio Pineda , Catalina
Tipo de recurso:
https://purl.org/coar/resource_type/c_7a1f
Fecha de publicación:
2024
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
spa
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oai:repositorio.unbosque.edu.co:20.500.12495/12088
Acceso en línea:
https://hdl.handle.net/20.500.12495/12088
Palabra clave:
Tabletas orodispersables
Colágeno tipo I
Desintegración
Mucoadhesión
615.19
Orodispersible tablets
Collagen type I
Disintegration
Mucoadhesion
Rights
openAccess
License
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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oai_identifier_str oai:repositorio.unbosque.edu.co:20.500.12495/12088
network_acronym_str UNBOSQUE2
network_name_str Repositorio U. El Bosque
repository_id_str
dc.title.none.fl_str_mv Diseño de sistemas orodispersables a base de colágeno tipo I
dc.title.translated.none.fl_str_mv Design of orodispersible systems based on type I collagen
title Diseño de sistemas orodispersables a base de colágeno tipo I
spellingShingle Diseño de sistemas orodispersables a base de colágeno tipo I
Tabletas orodispersables
Colágeno tipo I
Desintegración
Mucoadhesión
615.19
Orodispersible tablets
Collagen type I
Disintegration
Mucoadhesion
title_short Diseño de sistemas orodispersables a base de colágeno tipo I
title_full Diseño de sistemas orodispersables a base de colágeno tipo I
title_fullStr Diseño de sistemas orodispersables a base de colágeno tipo I
title_full_unstemmed Diseño de sistemas orodispersables a base de colágeno tipo I
title_sort Diseño de sistemas orodispersables a base de colágeno tipo I
dc.creator.fl_str_mv Rodriguez Ramirez, Valentina
Roncancio Pineda , Catalina
dc.contributor.advisor.none.fl_str_mv Jiménez Cruz, Ronald Andrés
dc.contributor.author.none.fl_str_mv Rodriguez Ramirez, Valentina
Roncancio Pineda , Catalina
dc.contributor.orcid.none.fl_str_mv Rodriguez Ramirez, Valentina [0009-0007-1643-6406]
Roncancio Pineda, Catalina [0009-0003-2401-9566]
dc.subject.none.fl_str_mv Tabletas orodispersables
Colágeno tipo I
Desintegración
Mucoadhesión
topic Tabletas orodispersables
Colágeno tipo I
Desintegración
Mucoadhesión
615.19
Orodispersible tablets
Collagen type I
Disintegration
Mucoadhesion
dc.subject.ddc.none.fl_str_mv 615.19
dc.subject.keywords.none.fl_str_mv Orodispersible tablets
Collagen type I
Disintegration
Mucoadhesion
description Contexto: Se propone el uso de colágeno tipo I en lugar de desintegrantes sintéticos comunes como crospovidona y croscarmelosa sódica, ofreciendo una alternativa natural con características hidrófilas, propiedades de hinchamiento en agua similares, que ofrece una excelente biocompatibilidad a un costo óptimo. Por tanto, el objetivo es el diseño, elaboración y caracterización de tabletas orodispersables a base de colágeno tipo I. Métodos: Se elaboraron tabletas orodispersables mediante compresión directa, utilizando estearato de zinc, dextrosa, crospovidona y colágeno tipo I como propuesta de desintegrante. Se varió la concentración de colágeno (0%, 0.5%, 2.5% y 5%) para evaluar su comportamiento usando pruebas de caracterización y análisis estadístico ANOVA. Resultados: Durante la prueba de desintegración, el colágeno causó un retraso en el tiempo atribuido al comportamiento viscoelástico. La incorporación de colágeno tipo I generó un aumento notable en el atributo de la mucoadhesión como se evidenció en la F3, F4 y F5. La formulación con 5% de colágeno tuvo el tiempo de humectación más prolongado de las formulaciones analizadas. Conclusiones: El colágeno en las concentraciones evaluadas no fue efectivo como desintegrante según pruebas de humectación y desintegración. No obstante, mostró potencial como excipiente mucoadhesivo y en la modulación de la liberación de fármacos.
publishDate 2024
dc.date.accessioned.none.fl_str_mv 2024-05-08T22:24:04Z
dc.date.available.none.fl_str_mv 2024-05-08T22:24:04Z
dc.date.issued.none.fl_str_mv 2024-04
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.local.none.fl_str_mv Tesis/Trabajo de grado - Monografía - Pregrado
dc.type.coar.none.fl_str_mv https://purl.org/coar/resource_type/c_7a1f
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/bachelorThesis
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format https://purl.org/coar/resource_type/c_7a1f
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12495/12088
dc.identifier.instname.spa.fl_str_mv Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
dc.identifier.repourl.none.fl_str_mv repourl:https://repositorio.unbosque.edu.co
url https://hdl.handle.net/20.500.12495/12088
identifier_str_mv Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
repourl:https://repositorio.unbosque.edu.co
dc.language.iso.fl_str_mv spa
language spa
dc.relation.references.none.fl_str_mv S. Bandar., R. Mittapalli., K., & R. Gannu, “Orodispersible tablets: An overview”. Asian Journal of Pharmaceutics, AJPS, vol. 2, no. 1, enero., pp. 1-2, 2008.
A. Abd Elbary., A. A. Ali., & H. M. Aboud, “Enhanced dissolution of meloxicam from orodispersible tablets prepared by different methods”. Bulletin of Faculty of Pharmacy, Cairo university, vol. 50, no. 2., pp. 89–97, 2012.
Pahwa, Gupta, and Ijpsr, “Superdisintegrants in the development of orally disintegrating tablets: A review,” vol. 2, no. 11, 2011.
S. Bauhuber, G. Warnke, and A. Berardi, “Disintegrant Selection in Hydrophobic Tablet Formulations,” J. Pharm. Sci., vol. 110, no. 5, pp. 2028–2037, 2021, doi: 10.1016/j.xphs.2020.11.002.
Bahadur, S., Roy, A., Chanda, R., Choudhury, A., Das, S., Saha, S., & Prasad, P. “Natural excipient development: need and future”. Asian Journal of Pharmaceutical Research, vol. 4, no. 1, pp. 12-15, 2014
J. Yang et al., “Novel Modification of Collagen: Realizing Desired Water Solubility and Thermostability in a Conflict-Free Way,” ACS Omega, vol. 5, no. 11, pp. 5772–5780, 2020, doi: 10.1021/acsomega.9b03846
I. N. Amirrah, Yogeswaran Lokanathan, Izzat Zulkiflee, F. Mohd, A. Motta, and Mh Busra Fauzi, “A Comprehensive Review on Collagen Type I Development of Biomaterials for Tissue Engineering: From Biosynthesis to Bioscaffold,” Biomedicines, vol. 10, no. 9, enero., pp. 2307–2307, Sep. 2022, doi: https://doi.org/10.3390/biomedicines10092307.
Nagar, P., Chauhan, I., & Yasir, M. “Insights into Polymers: Film Formers in Mouth Dissolving Films. Drug invention today”,vol. 3, no. 12, 2011.
Lee, Y. I., Lee, S. G., Kim, E., Jung, I., Suk, J., Kim, J., & Lee, J. H. (2021). “Anti‐aging effect of an oral disintegrating collagen film: a prospective, single‐arm study”. International Journal of Dermatology. doi:10.1111/ijd.15675.
D.Rubiano “Estudio de las propiedades viscoelásticas de dispersiones de colágeno tipo I empleadas como desintegrante de tabletas mediante análisis reológico dinámico,” Unbosque.edu.co, 2023.
Dey, P., & Sabyasachi Maiti. “Orodispersible tablets: A new trend in drug delivery”. Journal of Natural Science, Biology, and Medicine, vol.1, no. 1, pp. 2–2, 2010 https://doi.org/10.4103/0976-9668.71663.
P. Nagar, K. Singh, I. Chauhan, and N. Gupta, “Orally disintegrating tablets : Formulation, preparation techniques and evaluation,” ResearchGate, Jun. 2011.
L. L. Augsburger and S. W. Hoag. “Pharmaceutical Dosage Forms: Tablets”, Vol. 2, 3ª ed. New York: Informa Healthcare, 2008.
Kolling, William M. "Manual de excipientes farmacéuticos". Revista Estadounidense de Educación Farmacéutica vol.68,pp.1-5 ,2004
F. Luis and G. Moncayo, Manual de Tecnología farmacéutica, 10 ed. España, 2012.
Shuji Matsusaka and H. Masuda, “Electrostatics of particles,” Advanced Powder Technology, vol. 14, no. 2, pp. 143–166, 2003, doi: https://doi.org/10.1163/156855203763593958.
Ilgaz Akseli, N. Ladyzhynsky, J. Katz, and X. He, “Development of predictive tools to assess capping tendency of tablet formulations,” Powder Technology, vol. 236, pp. 139–148, 2013, doi: https://doi.org/10.1016/j.powtec.2012.04.026.
A. Singh Rana & S.L. Hari Kumar, “Manufacturing defects of tablets - A review”, Journal of Drug delivery & Therapeutics, vol,3, no.6, 2013.
J. Villar, "Factores que afectan a la compresión de comprimidos", trabajo fin de grado, Departamento de Farmacia y Tecnología Farmacéutica, Universidad De Sevilla, Sevilla, ESP, 2017.
Balamuralidhara Veeranna, Sreenivas S.A, H. V. Gangadharappa, and Pramodkumar. T.M, “Investigation on the Effect of Different Disintegrants on the Orodispersible Tablets of Rabeprazole,” ResearchGate, 2009.
N. N, K. P, K. R, R. S, D. R, and A. M, “PHARMACEUTICAL DILUENTS AND THEIR UNWANTED EFFECTS: A REVIEW,” Bulletin of Pharmaceutical Research, vol. 6, no. 2, pp. 45–49, 2016, doi: https://doi.org/10.21276/bpr.2016.6.2.2.
Hashikawa, Naohiro, et al. "Rapidly disintegrating tablet, and method for producing same." U.S. Patent No. 10,426,732. 1 Oct. 2019.
R. Rani Earle, L. Usha Ayalasomayajula, A. Naga Raju, K. Tanuja Kumari & P. Ravi Kumar, “Formulation and evaluation of diclofenac sodium orodispersible tablets using different superdisintegrants by direct compression technique”, ResearchGate, vol.8., no.8, pp. 4-6, 2016.
K. K. Saripella, Rama Mallipeddi, and S. H. Neau, “Crospovidone Interactions with Water. I. Calorimetric Study of the Effect of Polyplasdone Particle Size on Its Uptake and Distribution of Water,” Journal of Pharmaceutical Sciences, vol. 103, no. 2, pp. 669–675, Feb. 2014, doi: https://doi.org/10.1002/jps.23846.
B. Mitra, C. Wolfe, and S.-J. Wu, “Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations,” Drug Development and Industrial Pharmacy, vol. 44, no. 5, pp. 817–828, Jan. 2018, doi: https://doi.org/10.1080/03639045.2017.1414231.
José Eduardo Hernández-Torres and Luz María Melgoza-Contreras, “Principales superdisgregantes sintéticos, mecanismos y factores que influyen en su actividad,” Revista Colombiana de Ciencias Químico - Farmacéuticas, vol. 43, no. 2, pp. 234–247,2015, doi: https://doi.org/10.15446/rcciquifa.v43n2.54211.
Ganesh, NS y KB Deshpande. "Tabletas bucodispersables: una descripción general de la formulación y la tecnología". India: Revista Internacional de Ciencias Farmacéuticas y Bio. Hal ,pp.728-729,2011.
R.M. Pabari and Z. Ramtoola, “Effect of a Disintegration Mechanism on Wetting, Water Absorption, and Disintegration Time of Orodispersible Tablets,” Journal of Young Pharmacists, vol. 4, no. 3, pp. 157–163,2012,doi: https://doi.org/10.4103/0975-1483.100021
J. Quodbach and P. Kleinebudde, “A critical review on tablet disintegration,” Pharmaceutical Development and Technology, pp. 1–12, 2015, doi: https://doi.org/10.3109/10837450.2015.1045618.
Debyashreeta Barik et al., “Polymer–Protein Hybrid Network Involving Mucin: A Mineralized Biomimetic Template for Bone Tissue Engineering,” Macromolecular Bioscience, vol. 21, no. 6,2021, doi: https://doi.org/10.1002/mabi.202000381.
V. V. Khutoryanskiy, “Advances in Mucoadhesion and Mucoadhesive Polymers,” Macromolecular Bioscience, vol. 11, no. 6, pp. 748–764,2010, doi: https://doi.org/10.1002/mabi.201000388.
D. Ivarsson and M. Wahlgren, “Comparison of in vitro methods of measuring mucoadhesion: Ellipsometry, tensile strength and rheological measurements,” Colloids and surfaces. B, Biointerfaces (Print), vol. 92, pp. 353–359, 2012, doi: https://doi.org/10.1016/j.colsurfb.2011.12.020.
J. D. Smart, “Theories of Mucoadhesion,” pp. 159–174, 2014, doi: https://doi.org/10.1002/9781118794203.ch07.
S. Cheng, Z. Liu, and Q. Zhang, “Studies of factors influencing the disintegration performance of pesticide water dispersible granules,” Journal of Pesticide Science, vol. 40, no. 4, pp. 191–199, 2015, doi: https://doi.org/10.1584/jpestics.d15-030
Mohammadali Poursharifi Ghourichay, Seyed Hossein Kiaie, A. Nokhodchi, and Yousef Javadzadeh, “Formulation and Quality Control of Orally Disintegrating Tablets (ODTs): Recent Advances and Perspectives,” BioMed research international (Print), pp. 1–12,2021, doi: https://doi.org/10.1155/2021/6618934.
Powder Flow | USP,” Usp.org, 2023. https://www.usp.org/harmonization-standards/pdg/general-chapters/powder-flow (accessed Apr. 03, 2024).
P. Sriamornsak, N. Thirawong, and K. Korkerd, “Swelling, erosion and release behavior of alginate-based matrix tablets,” Eur. J. Pharm. Biopharm., vol. 66, no. 3, pp. 435–450, 2007, doi: 10.1016/j.ejpb.2006.12.003.
L. Alejandra, “Diseño, elaboración y caracterización de películas bicapa mucoadhesivas con aloe vera,” Unbosque.edu.co, 2022. https://repositorio.unbosque.edu.co/items/f95d4d9e-4b36-4ed3-95da-8d51dc3e63ca (accessed Apr. 03, 2024).
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spelling Jiménez Cruz, Ronald AndrésRodriguez Ramirez, ValentinaRoncancio Pineda , CatalinaRodriguez Ramirez, Valentina [0009-0007-1643-6406]Roncancio Pineda, Catalina [0009-0003-2401-9566]2024-05-08T22:24:04Z2024-05-08T22:24:04Z2024-04https://hdl.handle.net/20.500.12495/12088Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquerepourl:https://repositorio.unbosque.edu.coContexto: Se propone el uso de colágeno tipo I en lugar de desintegrantes sintéticos comunes como crospovidona y croscarmelosa sódica, ofreciendo una alternativa natural con características hidrófilas, propiedades de hinchamiento en agua similares, que ofrece una excelente biocompatibilidad a un costo óptimo. Por tanto, el objetivo es el diseño, elaboración y caracterización de tabletas orodispersables a base de colágeno tipo I. Métodos: Se elaboraron tabletas orodispersables mediante compresión directa, utilizando estearato de zinc, dextrosa, crospovidona y colágeno tipo I como propuesta de desintegrante. Se varió la concentración de colágeno (0%, 0.5%, 2.5% y 5%) para evaluar su comportamiento usando pruebas de caracterización y análisis estadístico ANOVA. Resultados: Durante la prueba de desintegración, el colágeno causó un retraso en el tiempo atribuido al comportamiento viscoelástico. La incorporación de colágeno tipo I generó un aumento notable en el atributo de la mucoadhesión como se evidenció en la F3, F4 y F5. La formulación con 5% de colágeno tuvo el tiempo de humectación más prolongado de las formulaciones analizadas. Conclusiones: El colágeno en las concentraciones evaluadas no fue efectivo como desintegrante según pruebas de humectación y desintegración. No obstante, mostró potencial como excipiente mucoadhesivo y en la modulación de la liberación de fármacos.PregradoQuímico FarmacéuticoContext: The use of type I collagen is proposed instead of common synthetic disintegrants such as crospovidone and croscarmellose sodium, offering a natural alternative with hydrophilic characteristics, similar swelling properties in water, offering excellent biocompatibility at an optimal cost. Therefore, the objective is the design, preparation and characterization of orodispersible tablets based on type I collagen. Methods: Orodispersible tablets are prepared by direct compression, using zinc stearate, dextrose, crospovidone and type I collagen as a proposed disintegrant. The collagen concentration was varied (0%, 0.5%, 2.5% and 5%) to evaluate its behavior using characterization tests and ANOVA statistical analysis. Results: During the disintegration test, collagen caused a time delay attributed to viscoelastic behavior. The incorporation of type collagen generated a notable increase in the mucoadhesion attribute as evidenced in F3, F4 and F5. The formulation with 5% collagen had the longest wetting time of the formulations analyzed. Conclusions: Collagen at the concentrations evaluated was not effective as a disintegrant according to wetting and disintegration tests. However, it showed potential as a mucoadhesive excipient and in modulating drug release.application/pdfAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Acceso abiertoinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Tabletas orodispersablesColágeno tipo IDesintegraciónMucoadhesión615.19Orodispersible tabletsCollagen type IDisintegrationMucoadhesionDiseño de sistemas orodispersables a base de colágeno tipo IDesign of orodispersible systems based on type I collagenQuímica FarmacéuticaUniversidad El BosqueFacultad de CienciasTesis/Trabajo de grado - Monografía - Pregradohttps://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesishttps://purl.org/coar/version/c_ab4af688f83e57aaS. Bandar., R. Mittapalli., K., & R. Gannu, “Orodispersible tablets: An overview”. Asian Journal of Pharmaceutics, AJPS, vol. 2, no. 1, enero., pp. 1-2, 2008.A. Abd Elbary., A. A. Ali., & H. M. Aboud, “Enhanced dissolution of meloxicam from orodispersible tablets prepared by different methods”. Bulletin of Faculty of Pharmacy, Cairo university, vol. 50, no. 2., pp. 89–97, 2012.Pahwa, Gupta, and Ijpsr, “Superdisintegrants in the development of orally disintegrating tablets: A review,” vol. 2, no. 11, 2011.S. Bauhuber, G. Warnke, and A. Berardi, “Disintegrant Selection in Hydrophobic Tablet Formulations,” J. Pharm. Sci., vol. 110, no. 5, pp. 2028–2037, 2021, doi: 10.1016/j.xphs.2020.11.002.Bahadur, S., Roy, A., Chanda, R., Choudhury, A., Das, S., Saha, S., & Prasad, P. “Natural excipient development: need and future”. Asian Journal of Pharmaceutical Research, vol. 4, no. 1, pp. 12-15, 2014J. Yang et al., “Novel Modification of Collagen: Realizing Desired Water Solubility and Thermostability in a Conflict-Free Way,” ACS Omega, vol. 5, no. 11, pp. 5772–5780, 2020, doi: 10.1021/acsomega.9b03846I. N. Amirrah, Yogeswaran Lokanathan, Izzat Zulkiflee, F. Mohd, A. Motta, and Mh Busra Fauzi, “A Comprehensive Review on Collagen Type I Development of Biomaterials for Tissue Engineering: From Biosynthesis to Bioscaffold,” Biomedicines, vol. 10, no. 9, enero., pp. 2307–2307, Sep. 2022, doi: https://doi.org/10.3390/biomedicines10092307.Nagar, P., Chauhan, I., & Yasir, M. “Insights into Polymers: Film Formers in Mouth Dissolving Films. Drug invention today”,vol. 3, no. 12, 2011.Lee, Y. I., Lee, S. G., Kim, E., Jung, I., Suk, J., Kim, J., & Lee, J. H. (2021). “Anti‐aging effect of an oral disintegrating collagen film: a prospective, single‐arm study”. International Journal of Dermatology. doi:10.1111/ijd.15675.D.Rubiano “Estudio de las propiedades viscoelásticas de dispersiones de colágeno tipo I empleadas como desintegrante de tabletas mediante análisis reológico dinámico,” Unbosque.edu.co, 2023.Dey, P., & Sabyasachi Maiti. “Orodispersible tablets: A new trend in drug delivery”. Journal of Natural Science, Biology, and Medicine, vol.1, no. 1, pp. 2–2, 2010 https://doi.org/10.4103/0976-9668.71663.P. Nagar, K. Singh, I. Chauhan, and N. Gupta, “Orally disintegrating tablets : Formulation, preparation techniques and evaluation,” ResearchGate, Jun. 2011.L. L. Augsburger and S. W. Hoag. “Pharmaceutical Dosage Forms: Tablets”, Vol. 2, 3ª ed. New York: Informa Healthcare, 2008.Kolling, William M. "Manual de excipientes farmacéuticos". Revista Estadounidense de Educación Farmacéutica vol.68,pp.1-5 ,2004F. Luis and G. Moncayo, Manual de Tecnología farmacéutica, 10 ed. España, 2012.Shuji Matsusaka and H. Masuda, “Electrostatics of particles,” Advanced Powder Technology, vol. 14, no. 2, pp. 143–166, 2003, doi: https://doi.org/10.1163/156855203763593958.Ilgaz Akseli, N. Ladyzhynsky, J. Katz, and X. He, “Development of predictive tools to assess capping tendency of tablet formulations,” Powder Technology, vol. 236, pp. 139–148, 2013, doi: https://doi.org/10.1016/j.powtec.2012.04.026.A. Singh Rana & S.L. Hari Kumar, “Manufacturing defects of tablets - A review”, Journal of Drug delivery & Therapeutics, vol,3, no.6, 2013.J. Villar, "Factores que afectan a la compresión de comprimidos", trabajo fin de grado, Departamento de Farmacia y Tecnología Farmacéutica, Universidad De Sevilla, Sevilla, ESP, 2017.Balamuralidhara Veeranna, Sreenivas S.A, H. V. Gangadharappa, and Pramodkumar. T.M, “Investigation on the Effect of Different Disintegrants on the Orodispersible Tablets of Rabeprazole,” ResearchGate, 2009.N. N, K. P, K. R, R. S, D. R, and A. M, “PHARMACEUTICAL DILUENTS AND THEIR UNWANTED EFFECTS: A REVIEW,” Bulletin of Pharmaceutical Research, vol. 6, no. 2, pp. 45–49, 2016, doi: https://doi.org/10.21276/bpr.2016.6.2.2.Hashikawa, Naohiro, et al. 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Alejandra, “Diseño, elaboración y caracterización de películas bicapa mucoadhesivas con aloe vera,” Unbosque.edu.co, 2022. https://repositorio.unbosque.edu.co/items/f95d4d9e-4b36-4ed3-95da-8d51dc3e63ca (accessed Apr. 03, 2024).spaORIGINALTrabajo de grado.pdfTrabajo de grado.pdfapplication/pdf3239909https://repositorio.unbosque.edu.co/bitstreams/9e992ff3-8da3-435b-8d25-1b087e6d81b3/downloadb31280486b7893b10e71ba75d683c37fMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82000https://repositorio.unbosque.edu.co/bitstreams/a34f0740-4879-4451-80a2-41acf3f08785/download17cc15b951e7cc6b3728a574117320f9MD54Carta de autorización.pdfapplication/pdf192294https://repositorio.unbosque.edu.co/bitstreams/a89c5d24-5e69-4172-8d7b-a448e1a39ab2/download027c9ae448efb3f3f3161b5ffc67d915MD55Anexo 1 Acta de aprobación.pdfapplication/pdf691233https://repositorio.unbosque.edu.co/bitstreams/cc136402-9d8a-44bc-9783-f3a38cf936a9/download6b38e4cbb056dc179680eaa6e5c62f9cMD56TEXTTrabajo de grado.pdf.txtTrabajo de grado.pdf.txtExtracted texttext/plain57471https://repositorio.unbosque.edu.co/bitstreams/6656b563-7535-4aa8-b4e2-fb1adccda087/download4966d9444ae1c68b9ac3fbccf047a220MD57THUMBNAILTrabajo de grado.pdf.jpgTrabajo de grado.pdf.jpgGenerated Thumbnailimage/jpeg4892https://repositorio.unbosque.edu.co/bitstreams/dc8e9546-7330-4a32-9c76-d33a79eda210/downloade26ed45feb6a547af619ba3b94f905d2MD5820.500.12495/12088oai:repositorio.unbosque.edu.co:20.500.12495/120882024-05-09 03:03:39.824http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internacionalopen.accesshttps://repositorio.unbosque.edu.coRepositorio Institucional Universidad El Bosquebibliotecas@biteca.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