Correo Electrónico
DNINFOA - SIA
Bibliotecas
Convocatorias
Identidad U.N.
Publicado
Caracterización fisicoquímica y evaluación in vitro de sistemas autoemulsionables de liberación de indometacina
Physicochemical characterization and in vitro evaluation of selfemulsifying indomethacin release systems
Caracterização físico-química e avaliação in vitro de sistemas autoemulsificantes de liberação de indometacina
DOI:
https://doi.org/10.15446/rcciquifa.v51n1.95366Palabras clave:
Indometacina, solubilidad, disolución, formulaciones lipídicas (es)Indomethacin, solubility, dissolution, lipid formulations (en)
Indometacina, solubilidade, dissolução, formulações lipídicas (pt)
Descargas
Objetivo: incorporar la indometacina en sistemas autoemulsionables de liberación con la finalidad de aumentar su solubilidad en medio acuoso, la velocidad de disolución y permeación in vitro. Metodología: se llevaron a cabo ensayos de solubilidad al equilibrio para preparar formulaciones con los excipientes, en los cuales la indometacina presentó mayor incremento de solubilidad; los sistemas fueron caracterizados por medio del tiempo de autoemulsificación, estabilidad física, tamaño de partícula, potencial zeta, perfiles de disolución y permeación a través de membrana sintética. Resultados: el diseño experimental de los sistemas autoemulsionables de liberación permitió crear formulaciones que aumentaron la solubilidad de la indometacina en un orden de 105 veces con respecto a la solubilidad acuosa. Las formulaciones que resultaron viables presentaron tiempos de autoemulsificación menores que 60 segundos, además, las distribuciones de tamaño de partícula de las dispersiones fueron inferiores a los 300 nm, presentó índices de polidispersión inferiores a 0,3 y valores de potencial zeta menores de -25 mV. Los perfiles de disolución mostraron que las formulaciones cumplen con un valor de factor de similitud mayor que 50, además, la permeabilidad a través de membrana sintética es mayor para las formulaciones autoemulsionables que el producto de referencia. Conclusiones: la formulación de indometacina en sistemas autoemulsionables de liberación incrementa la solubilidad en medio acuoso, aumenta la disolución y liberación. Estos resultados sugieren que la administración oral de indometacina incorporada en sistemas autoemulsionables puede acelerar el inicio del efecto farmacológico.
Aim: To load indomethacin into self-emulsifying delivery systems in order to increase, water-solubility, rate dissolution and in vitro permeation. Methodology: Equilibrium solubility tests were carried out to prepare formulations with the excipients, in which indomethacin presented a greater increase in solubility; the systems were characterized by self-emulsification time, physical stability, particle size, zeta potential, dissolution profiles and permeation through synthetic membrane. Results: The experimental design of self-emulsifying delivery systems allowed to create formulations that increase the solubility of indomethacin in an order of 105 times with respect to the aqueous solubility. The feasible formulations presented autoemulsification times less than 60 seconds, in addition, the particle size distributions of the dispersions were less than 300 nm, with polydispersity index smaller than 0.3, and zeta potential values lower than -25 mV. The dissolution profiles showed that the formulations comply with a similarity factor value greater than 50, in addition, the permeability through a synthetic membrane is higher for the selfemulsifying formulations than the reference product. Conclusion: The formulation of indomethacin into self-emulsifying delivery systems enhances the solubility in aqueous medium, increases dissolution and accelerate release. These results suggest that the oral administration of indomethacin incorporated into self-emulsifying delivery systems can accelerate the onset of the pharmacological effect.
Objetivo: incorporar a indometacina em sistemas de liberação autoemulsificantes a fim de aumentar sua solubilidade em meio aquoso, a taxa de dissolução e permeação in vitro. Metodologia: foram realizados testes de solubilidade de equilíbrio para preparar formulações com os excipientes, nas quais a indometacina apresentou maior aumento na solubilidade; os sistemas foram caracterizados quanto ao tempo de autoemulsificação, estabilidade física, tamanho de partícula, potencial zeta, perfis de dissolução e permeação através de membrana sintética. Resultados: o desenho experimental dos sistemas de liberação autoemulsificantes permitiu a criação de formulações que aumentaram a solubilidade da indometacina na ordem de 105 vezes em relação à solubilidade aquosa. As formulações que se mostraram viáveis apresentaram tempos de autoemulsificação inferiores a 60 segundos, além disso, as distribuições granulométricas das dispersões foram inferiores a 300 nm, apresentaram índices de polidispersidadeinferiores a 0,3 e valores de potencial zeta inferiores a-25 mV.
Os perfis de dissolução mostraram que as formulações atendem a um valor de fator de similaridade maior que 50, além disso, a permeabilidade através da membrana sintética é maior para as formulações autoemulsionantes do que para o produto de referência. Conclusões: a formulação de indometacina em sistemas de liberação autoemulsificantes aumenta a solubilidade em meio aquoso, aumenta a dissolução e a liberação. Esses resultados sugerem que a administração oral de indometacina incorporada em sistemas autoemulsificantes pode acelerar o início do efeito farmacológico.
Referencias
M.J. Qureshi, C. Mallikarjun, W.G. Kian, Enhancement of solubility and therapeutic potential of poorly soluble lovastatin by SMEDDS formulation adsorbed on directly compressed spray dried magnesium aluminometasilicate liquid loadable tablets: a study in diet induced hyperlipidemic rabbits, Asian J. Pharm. Sci., 10(1), 40-56 (2015). DOI: https://doi.org/10.1016/j.ajps.2014.08.003
A. Chaudhary, U. Nagaich, N. Gulati, et al., Enhancement of solubilization and bioavailability of poorly soluble drugs by physical and chemical modifications: A recent review, J. Adv. Pharm. Educ. Res., 2(1), 32-67 (2012).
V.R. Vemula, V. Lagishetty, S. Lingala, Solubility enhancement techniques, Int. J. Pharm. Sci. Rev. Res., 5(1), 41-51 (2010). DOI: https://doi.org/10.1002/chin.201141266
A. Czajkowska-Kośnik, M. Szekalska, A. Amelian, et al., Development and evaluation of liquid and solid self-emulsifying drug delivery systems for atorvastatin, Molecules, 20(12), 21010-21022 (2015). DOI: https://doi.org/10.3390/molecules201219745
D.G. Fatouros, G.R. Deen, L. Arleth, et al., Structural development of self nano emulsifying drug delivery systems (SNEDDS) during in vitro lipid digestion monitored by small-angle X-ray scattering, Pharm. Res., 24(10), 1844-1853 (2007). DOI: https://doi.org/10.1007/s11095-007-9304-6
E. Atef, A.A. Belmonte, Formulation and in vitro and in vivo characterization of a phenytoin self-emulsifying drug delivery system (SEDDS), Eur. J. Pharm. Sci., 35(4), 257-263 (2008). DOI: https://doi.org/10.1016/j.ejps.2008.07.004
J.Ø. Christensen, K. Schultz, B. Mollgaard, et al., Solubilisation of poorly watersoluble drugs during in vitro lipolysis of medium and long-chain triacylglycerols, Eur. J. Pharm. Sci., 23(3), 287-296 (2004). DOI: https://doi.org/10.1016/j.ejps.2004.08.003
H.D. Williams, N.L. Trevaskis, S.A. Charman, et al., Strategies to address low drug solubility in discovery and development, Pharmacol. Rev., 65(1), 315-499 (2013). DOI: https://doi.org/10.1124/pr.112.005660
V. Jannin, J.-D. Rodier, J. Musakhanian, Polyoxylglycerides and glycerides: effects of manufacturing parameters on API stability, excipient functionality and processing, Int. J. Pharm., 466(1-2), 109-121 (2014). DOI: https://doi.org/10.1016/j.ijpharm.2014.03.007
V. Jannin, J. Musakhanian, D. Marchaud, Approaches for the development of solid and semi-solid lipid-based formulations, Adv. Drug Deliv. Rev., 60(6), 734-746 (2008). DOI: https://doi.org/10.1016/j.addr.2007.09.006
M. de Lourdes-Garzón, M.L. Vázquez, L. Villafuerte, et al., Efecto de los componentes de la formulación en las propiedades de las nanopartículas lipídicas sólidas, Rev. Mexic. Cienc. Farm., 40(2), 26-40 (2009).
B.K. Poudel, N. Marasini, T.H. Tran, et al., Formulation, characterization and optimization of valsartan self-microemulsifying drug delivery system using statistical design of experiment, Chem. Pharm. Bull., 60(11), 1409-1418 (2012). DOI: https://doi.org/10.1248/cpb.c12-00502
C. Martínez, Desarrollo de micro y nanoemulsiones de liberación sostenida, Trabajo de Grado, Facultad de Farmacia, Universidad Complutense de Madrid, 2016, 20 p.
F. Shakeel, N. Haq, M. El-Badry, et al., Ultra fine super self-nanoemulsifying drug delivery system (SNEDDS) enhanced solubility and dissolution of indomethacin, J. Mol. Liq., 180, 89-94 (2013). DOI: https://doi.org/10.1016/j.molliq.2013.01.008
F. Shakeel, N. Haq, F.K. Alanazi, et al., Impact of various nonionic surfactants on self-nanoemulsification efficiency of two grades of Capryol (Capryol-90 and Capryol-PGMC), J. Mol. Liq., 182, 57-63 (2013). DOI: https://doi.org/10.1016/j.molliq.2013.03.011
S.K. Mutyam, N.K. Bejugam, H.J. Parish, et al., Permeability enhancing lipidbased co-solvent and SEDDS formulations of SQ641, an antimycobacterial agent, Pharm. Develop. Technol., 20(5), 598-607 (2015). DOI: https://doi.org/10.3109/10837450.2014.908304
V. Jannin, S. Chevrier, M. Michenaud, et al., Development of self emulsifying lipid formulations of BCS class II drugs with low to medium lipophilicity, Int. J. Pharm., 495(1), 385-392 (2015). DOI: https://doi.org/10.1016/j.ijpharm.2015.09.009
H.D. Williams, M.U. Anby, P. Sassene, et al., Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion, Mol. Pharm., 9(11), 3286-3300 (2012). DOI: https://doi.org/10.1021/mp300331z
D.J. McClements, Nanoemulsions versus microemulsions: terminology, differences, and similarities, Soft Matter, 8(6), 1719-1729 (2012). DOI: https://doi.org/10.1039/C2SM06903B
H. Devalapally, S. Silchenko, F. Zhou, et al., Evaluation of a nanoemulsion formulation strategy for oral bioavailability enhancement of danazol in rats and dogs, J. Pharm. Sci., 102(10), 3808-3815 (2013). DOI: https://doi.org/10.1002/jps.23667
J.H. Kang, D.H. Oh, Y.-K. Oh, et al., Effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in solid self-nanoemulsifying drug delivery system (solid SNEDDS), Eur. J. Pharm. Biopharm., 80(2), 289-297 (2012). DOI: https://doi.org/10.1016/j.ejpb.2011.11.005
L. Helleberg, Clinical pharmacokinetics of indomethacin, Clin. Pharmacokin., 6(4), 245-258 (1981). DOI: https://doi.org/10.2165/00003088-198106040-00001
J.R. Medina-López, M. Hurtado y de la Peña, A.R. Cortés-Arroyo, et al., Disolución comparativa de indometacina en cápsulas utilizando los Aparatos 1 y 4 USP, Rev. Mexic. Cienc. Farm., 43(3), 72-80 (2012).
P.M.A. Chéry, P. Mitchell, Manual de farmacología básica y clínica, 6a ed., McGraw-Hill Interamericana, 2013.
A. Patel, N. Sharma, A. Kumar, Self emulsifying drug delivery system: a gentle approach for drug delivery, Int. J. Drug Deliv., 4(3), 297 (2012).
A.C. Moffat, M.D. Osselton, B. Widdop, et al., Clarke’s analysis of drugs and poisons, Vol. 3, Pharmaceutical Press, London, 2011.
D.C. Harris, Quantitative chemical analysis, MacMillan, 2010.
C.M. Laing, J.A. Rankin, Odds ratios and confidence intervals: a review for the pediatric oncology clinician, J. Pediatr. Oncol. Nursing, 28(6), 363-367 (2011). DOI: https://doi.org/10.1177/1043454211426575
C.W. Pouton, Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems, Eur. J. Pharm. Sci., 11, S93-S98 (2000). DOI: https://doi.org/10.1016/S0928-0987(00)00167-6
C.W. Pouton, Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system, Eur. J. Pharm. Sci., 29(3-4), 278-287 (2006). DOI: https://doi.org/10.1016/j.ejps.2006.04.016
F.U. Rehman, K.U. Shah, S.U. Shah, et al., From nanoemulsions to self-nanoemulsions, with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS), Expert Opin. Drug Deliv., 14(11), 1325-1340 (2017). DOI: https://doi.org/10.1080/17425247.2016.1218462
M.A. Rahman, A. Hussain, M.S. Hussain, et al., Role of excipients in successful development of self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS), Drug Develop. Ind. Pharm., 39(1), 1-19 (2013). DOI: https://doi.org/10.3109/03639045.2012.660949
O.M. Feeney, M.F. Crum, C.L. McEvoy, et al., 50 years of oral lipid-based formulations: provenance, progress and future perspectives, Adv. Drug Deliv. Rev., 101, 167-194 (2016). DOI: https://doi.org/10.1016/j.addr.2016.04.007
R.C. Rowe, P. Sheskey, M. Quinn, Handbook of pharmaceutical excipients, Pharmaceutical Press, London, 2009.
F. Shakeel, N. Haq, F.K. Alanazi, et al., Self-nanoemulsifying performance of two grades of Lauroglycol (Lauroglycol-90 and Lauroglycol-FCC) in the presence of mixed nonionic surfactants, Pharm. Develop. Technol., 19(7), 799-805 (2014). DOI: https://doi.org/10.3109/10837450.2013.829099
Q. Tian, F. Ren, Z. Xu, et al., Preparation of high solubilizable microemulsion of naproxen and its solubilization mechanism, Int. J. Pharm., 426(1-2), 202-210 (2012). DOI: https://doi.org/10.1016/j.ijpharm.2012.01.019
V.R. Kallakunta, B.B. Eedara, R. Jukanti, et al., A Gelucire 44/14 and labrasol based solid self emulsifying drug delivery system: formulation and evaluation, J. Pharm. Invest., 43(3), 185-196 (2013). DOI: https://doi.org/10.1007/s40005-013-0060-9
K. Sapra, A. Sapra, S. Singh, et al., Self emulsifying drug delivery system: A tool in solubility enhancement of poorly soluble drugs, Indo Global J. Pharm. Sci., 2(3), 313-332 (2012). DOI: https://doi.org/10.35652/IGJPS.2012.37
Cómo citar
APA
ACM
ACS
ABNT
Chicago
Harvard
IEEE
MLA
Turabian
Vancouver
Descargar cita
Licencia
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
El Departamento de Farmacia de la Facultad de Ciencias de la Universidad Nacional de Colombia autoriza la fotocopia de artículos y textos para fines de uso académico o interno de las instituciones citando la fuente. Las ideas emitidas por los autores son responsabilidad expresa de estos y no de la revista.
Todo el contenido de esta revista, excepto dónde está identificado, está bajo una Licencia Creative Commons de Atribución 4.0 aprobada en Colombia. Consulte la normativa en: http://co.creativecommons.org/?page_id=13
