Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate

Dong Shik Kim1,*, Jung Hyun Cho1,*, Jong Hyuck Park,1 Jung Suk Kim,1 Eon Soo Song,2 Jaewook Kwon,2 Bhupendra Raj Giri,2 Sung Giu Jin,3 Kyeong Soo Kim,4 Han-Gon Choi,1 Dong Wuk Kim21College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Kore...

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Autores principales:	Kim DS, Cho JH, Park JH, Kim JS, Song ES, Kwon J, Giri BR, Jin SG, Kim KS, Choi HG, Kim DW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Methotrexate Solid SMEDDS Solubility Bioavailability Photostability. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b80d15b82a1b48238f3d4fcb5870c405
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spelling	oai:doaj.org-article:b80d15b82a1b48238f3d4fcb5870c4052021-12-02T00:15:43ZSelf-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate1178-2013https://doaj.org/article/b80d15b82a1b48238f3d4fcb5870c4052019-07-01T00:00:00Zhttps://www.dovepress.com/self-microemulsifying-drug-delivery-system-smedds-for-improved-oral-de-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dong Shik Kim1,, Jung Hyun Cho1,, Jong Hyuck Park,1 Jung Suk Kim,1 Eon Soo Song,2 Jaewook Kwon,2 Bhupendra Raj Giri,2 Sung Giu Jin,3 Kyeong Soo Kim,4 Han-Gon Choi,1 Dong Wuk Kim21College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea; 2College of Pharmacy & Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea; 3Department of Pharmaceutical Engineering, Dankook University, Cheonan, South Korea; 4Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology, Jinju, South Korea*These authors contributed equally to this workPurpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability.Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder.Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions.Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.Keywords: methotrexate, solid SMEDDS, solubility, bioavailability, photostabilityKim DSCho JHPark JHKim JSSong ESKwon JGiri BRJin SGKim KSChoi HGKim DWDove Medical PressarticleMethotrexateSolid SMEDDSSolubilityBioavailabilityPhotostability.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 4949-4960 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Methotrexate Solid SMEDDS Solubility Bioavailability Photostability. Medicine (General) R5-920
spellingShingle	Methotrexate Solid SMEDDS Solubility Bioavailability Photostability. Medicine (General) R5-920 Kim DS Cho JH Park JH Kim JS Song ES Kwon J Giri BR Jin SG Kim KS Choi HG Kim DW Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate
description	Dong Shik Kim1,, Jung Hyun Cho1,, Jong Hyuck Park,1 Jung Suk Kim,1 Eon Soo Song,2 Jaewook Kwon,2 Bhupendra Raj Giri,2 Sung Giu Jin,3 Kyeong Soo Kim,4 Han-Gon Choi,1 Dong Wuk Kim21College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea; 2College of Pharmacy & Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea; 3Department of Pharmaceutical Engineering, Dankook University, Cheonan, South Korea; 4Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology, Jinju, South Korea*These authors contributed equally to this workPurpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability.Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder.Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions.Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.Keywords: methotrexate, solid SMEDDS, solubility, bioavailability, photostability
format	article
author	Kim DS Cho JH Park JH Kim JS Song ES Kwon J Giri BR Jin SG Kim KS Choi HG Kim DW
author_facet	Kim DS Cho JH Park JH Kim JS Song ES Kwon J Giri BR Jin SG Kim KS Choi HG Kim DW
author_sort	Kim DS
title	Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate
title_short	Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate
title_full	Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate
title_fullStr	Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate
title_full_unstemmed	Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate
title_sort	self-microemulsifying drug delivery system (smedds) for improved oral delivery and photostability of methotrexate
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/b80d15b82a1b48238f3d4fcb5870c405
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Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate

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