Optimized formulation of solid self-microemulsifying sirolimus delivery systems

Wonkyung Cho,1,2 Min-Soo Kim,3 Jeong-Soo Kim,2 Junsung Park,1,2 Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Jeong-Sook Park,2 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Cho W, Kim MS, Kim JS, Park J, Park HJ, Cha KH, Park JS, Hwang SJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7134d2a54d5843f9a1f5b1fdc28c0bd5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7134d2a54d5843f9a1f5b1fdc28c0bd5
record_format	dspace
spelling	oai:doaj.org-article:7134d2a54d5843f9a1f5b1fdc28c0bd52021-12-02T03:17:09ZOptimized formulation of solid self-microemulsifying sirolimus delivery systems1176-91141178-2013https://doaj.org/article/7134d2a54d5843f9a1f5b1fdc28c0bd52013-04-01T00:00:00Zhttp://www.dovepress.com/optimized-formulation-of-solid-self-microemulsifying-sirolimus-deliver-a12889https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Wonkyung Cho,1,2 Min-Soo Kim,3 Jeong-Soo Kim,2 Junsung Park,1,2 Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Jeong-Sook Park,2 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea Background: The aim of this study was to develop an optimized solid self-microemulsifying drug delivery system (SMEDDS) formulation for sirolimus to enhance its solubility, stability, and bioavailability. Methods: Excipients used for enhancing the solubility and stability of sirolimus were screened. A phase-separation test, visual observation for emulsifying efficiency, and droplet size analysis were performed. Ternary phase diagrams were constructed to optimize the liquid SMEDDS formulation. The selected liquid SMEDDS formulations were prepared into solid form. The dissolution profiles and pharmacokinetic profiles in rats were analyzed. Results: In the results of the oil and cosolvent screening studies, Capryol™ Propylene glycol monocaprylate (PGMC) and glycofurol exhibited the highest solubility of all oils and cosolvents, respectively. In the surfactant screening test, D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was determined to be the most effective stabilizer of sirolimus in pH 1.2 simulated gastric fluids. The optimal formulation determined by the construction of ternary phase diagrams was the T32 (Capryol™ PGMC:glycofurol:vitamin E TPGS = 30:30:40 weight ratio) formulation with a mean droplet size of 108.2 ± 11.4 nm. The solid SMEDDS formulations were prepared with Sucroester 15 and mannitol. The droplet size of the reconstituted solid SMEDDS showed no significant difference compared with the liquid SMEDDS. In the dissolution study, the release amounts of sirolimus from the SMEDDS formulation were significantly higher than the raw sirolimus powder. In addition, the solid SMEDDS formulation was in a more stable state than liquid SMEDDS in pH 1.2 simulated gastric fluids. The results of the pharmacokinetic study indicate that the SMEDDS formulation shows significantly greater bioavailability than the raw sirolimus powder or commercial product (Rapamune® oral solution). Conclusion: The results of this study suggest the potential use of a solid SMEDDS formulation for the delivery of poorly water-soluble drugs, such as sirolimus, through oral administration. Keywords: sirolimus, solubility, stability, bioavailability, self-emulsifying drug delivery systems, microemulsionCho WKim MSKim JSPark JPark HJCha KHPark JSHwang SJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1673-1682 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Cho W Kim MS Kim JS Park J Park HJ Cha KH Park JS Hwang SJ Optimized formulation of solid self-microemulsifying sirolimus delivery systems
description	Wonkyung Cho,1,2 Min-Soo Kim,3 Jeong-Soo Kim,2 Junsung Park,1,2 Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Jeong-Sook Park,2 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea Background: The aim of this study was to develop an optimized solid self-microemulsifying drug delivery system (SMEDDS) formulation for sirolimus to enhance its solubility, stability, and bioavailability. Methods: Excipients used for enhancing the solubility and stability of sirolimus were screened. A phase-separation test, visual observation for emulsifying efficiency, and droplet size analysis were performed. Ternary phase diagrams were constructed to optimize the liquid SMEDDS formulation. The selected liquid SMEDDS formulations were prepared into solid form. The dissolution profiles and pharmacokinetic profiles in rats were analyzed. Results: In the results of the oil and cosolvent screening studies, Capryol™ Propylene glycol monocaprylate (PGMC) and glycofurol exhibited the highest solubility of all oils and cosolvents, respectively. In the surfactant screening test, D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was determined to be the most effective stabilizer of sirolimus in pH 1.2 simulated gastric fluids. The optimal formulation determined by the construction of ternary phase diagrams was the T32 (Capryol™ PGMC:glycofurol:vitamin E TPGS = 30:30:40 weight ratio) formulation with a mean droplet size of 108.2 ± 11.4 nm. The solid SMEDDS formulations were prepared with Sucroester 15 and mannitol. The droplet size of the reconstituted solid SMEDDS showed no significant difference compared with the liquid SMEDDS. In the dissolution study, the release amounts of sirolimus from the SMEDDS formulation were significantly higher than the raw sirolimus powder. In addition, the solid SMEDDS formulation was in a more stable state than liquid SMEDDS in pH 1.2 simulated gastric fluids. The results of the pharmacokinetic study indicate that the SMEDDS formulation shows significantly greater bioavailability than the raw sirolimus powder or commercial product (Rapamune® oral solution). Conclusion: The results of this study suggest the potential use of a solid SMEDDS formulation for the delivery of poorly water-soluble drugs, such as sirolimus, through oral administration. Keywords: sirolimus, solubility, stability, bioavailability, self-emulsifying drug delivery systems, microemulsion
format	article
author	Cho W Kim MS Kim JS Park J Park HJ Cha KH Park JS Hwang SJ
author_facet	Cho W Kim MS Kim JS Park J Park HJ Cha KH Park JS Hwang SJ
author_sort	Cho W
title	Optimized formulation of solid self-microemulsifying sirolimus delivery systems
title_short	Optimized formulation of solid self-microemulsifying sirolimus delivery systems
title_full	Optimized formulation of solid self-microemulsifying sirolimus delivery systems
title_fullStr	Optimized formulation of solid self-microemulsifying sirolimus delivery systems
title_full_unstemmed	Optimized formulation of solid self-microemulsifying sirolimus delivery systems
title_sort	optimized formulation of solid self-microemulsifying sirolimus delivery systems
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/7134d2a54d5843f9a1f5b1fdc28c0bd5
work_keys_str_mv	AT chow optimizedformulationofsolidselfmicroemulsifyingsirolimusdeliverysystems AT kimms optimizedformulationofsolidselfmicroemulsifyingsirolimusdeliverysystems AT kimjs optimizedformulationofsolidselfmicroemulsifyingsirolimusdeliverysystems AT parkj optimizedformulationofsolidselfmicroemulsifyingsirolimusdeliverysystems AT parkhj optimizedformulationofsolidselfmicroemulsifyingsirolimusdeliverysystems AT chakh optimizedformulationofsolidselfmicroemulsifyingsirolimusdeliverysystems AT parkjs optimizedformulationofsolidselfmicroemulsifyingsirolimusdeliverysystems AT hwangsj optimizedformulationofsolidselfmicroemulsifyingsirolimusdeliverysystems
_version_	1718401861865701376

Optimized formulation of solid self-microemulsifying sirolimus delivery systems

Ejemplares similares