Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor

Young-Guk Na,1 Jin-Ju Byeon,1 Miao Wang,1 Hyun Wook Huh,1 Gi-Ho Son,1,2 Sung-Hoon Jeon,1,3 Ki-Hyun Bang,1,2 Sung-Jin Kim,1 Hye-Jin Lee,1 Hong-Ki Lee,1 Cheong-Weon Cho1 1College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 2Korea United Pharmaceutical Co. Ltd., Sejong, Repu...

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Autores principales:	Na YG, Byeon JJ, Wang M, Huh HW, Son GH, Jeon SH, Bang KH, Kim SJ, Lee HJ, Lee HK, Cho CW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Ticagrelor SMEDDS Optimization Bioavailability Platelet aggregation Antiplatelet activity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5c9da4c1f51f4a8abf3978d691dd4b4e
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spelling	oai:doaj.org-article:5c9da4c1f51f4a8abf3978d691dd4b4e2021-12-02T07:58:14ZStrategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor1178-2013https://doaj.org/article/5c9da4c1f51f4a8abf3978d691dd4b4e2019-02-01T00:00:00Zhttps://www.dovepress.com/strategic-approach-to-developing-a-self-microemulsifying-drug-delivery-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Young-Guk Na,1 Jin-Ju Byeon,1 Miao Wang,1 Hyun Wook Huh,1 Gi-Ho Son,1,2 Sung-Hoon Jeon,1,3 Ki-Hyun Bang,1,2 Sung-Jin Kim,1 Hye-Jin Lee,1 Hong-Ki Lee,1 Cheong-Weon Cho1 1College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 2Korea United Pharmaceutical Co. Ltd., Sejong, Republic of Korea; 3SamA Pharmaceutical Co. Ltd., Suwon, Republic of Korea Background: Ticagrelor (TCG) is used to inhibit platelet aggregation in patients with acute coronary syndrome, but its poor solubility and low bioavailability limit its in vivo efficacy. The purpose of this study was to manufacture an optimized TCG-loaded self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability and antiplatelet activity of TCG. Materials and methods: Solubility and emulsification tests were conducted to determine the most suitable oils, surfactants, and cosurfactants. Scheffé’s mixture design was applied to optimize the percentage of each component applied in the SMEDDS formulation to achieve optimal physical characteristics, ie, high solubility of TCG in SMEDDS, small droplet size, low precipitation, and high transmittance. Results: The optimized TCG-loaded SMEDDS (TCG-SM) formulation composed of 10.0% Capmul MCM (oil), 53.8% Cremophor EL (surfactant), and 36.2% Transcutol P (cosurfactant) significantly improving the dissolution of TCG in various media compared with TCG in Brilinta® (commercial product). TCG-SM exhibited higher cellular uptake and permeability in Caco-2 cells than raw TCG suspension. In pharmacokinetic studies in rats, TCG-SM exhibited higher oral bioavailability with 5.7 and 6.4 times higher area under the concentration–time curve and maximum plasma concentration, respectively, than a raw TCG suspension. Antiplatelet activity studies exhibited that the TCG-SM formulation showed significantly improved inhibition of platelet aggregation compared with raw TCG at the same dose of TCG. And, a 10 mg/kg dose of raw TCG suspension and a 5 mg/kg dose of TCG-SM had a similar area under the inhibitory curve (907.0%±408.8% and 907.8%±200.5%·hours, respectively) for antiplatelet activity. Conclusion: These results suggest that the developed TCG-SM could be successfully used as an efficient method to achieve the enhanced antiplatelet activity and bioavailability of TCG. Keywords: ticagrelor, SMEDDS, optimization, bioavailability, platelet aggregation, antiplatelet activityNa YGByeon JJWang MHuh HWSon GHJeon SHBang KHKim SJLee HJLee HKCho CWDove Medical PressarticleTicagrelorSMEDDSOptimizationBioavailabilityPlatelet aggregationAntiplatelet activityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1193-1212 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ticagrelor SMEDDS Optimization Bioavailability Platelet aggregation Antiplatelet activity Medicine (General) R5-920
spellingShingle	Ticagrelor SMEDDS Optimization Bioavailability Platelet aggregation Antiplatelet activity Medicine (General) R5-920 Na YG Byeon JJ Wang M Huh HW Son GH Jeon SH Bang KH Kim SJ Lee HJ Lee HK Cho CW Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor
description	Young-Guk Na,1 Jin-Ju Byeon,1 Miao Wang,1 Hyun Wook Huh,1 Gi-Ho Son,1,2 Sung-Hoon Jeon,1,3 Ki-Hyun Bang,1,2 Sung-Jin Kim,1 Hye-Jin Lee,1 Hong-Ki Lee,1 Cheong-Weon Cho1 1College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 2Korea United Pharmaceutical Co. Ltd., Sejong, Republic of Korea; 3SamA Pharmaceutical Co. Ltd., Suwon, Republic of Korea Background: Ticagrelor (TCG) is used to inhibit platelet aggregation in patients with acute coronary syndrome, but its poor solubility and low bioavailability limit its in vivo efficacy. The purpose of this study was to manufacture an optimized TCG-loaded self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability and antiplatelet activity of TCG. Materials and methods: Solubility and emulsification tests were conducted to determine the most suitable oils, surfactants, and cosurfactants. Scheffé’s mixture design was applied to optimize the percentage of each component applied in the SMEDDS formulation to achieve optimal physical characteristics, ie, high solubility of TCG in SMEDDS, small droplet size, low precipitation, and high transmittance. Results: The optimized TCG-loaded SMEDDS (TCG-SM) formulation composed of 10.0% Capmul MCM (oil), 53.8% Cremophor EL (surfactant), and 36.2% Transcutol P (cosurfactant) significantly improving the dissolution of TCG in various media compared with TCG in Brilinta® (commercial product). TCG-SM exhibited higher cellular uptake and permeability in Caco-2 cells than raw TCG suspension. In pharmacokinetic studies in rats, TCG-SM exhibited higher oral bioavailability with 5.7 and 6.4 times higher area under the concentration–time curve and maximum plasma concentration, respectively, than a raw TCG suspension. Antiplatelet activity studies exhibited that the TCG-SM formulation showed significantly improved inhibition of platelet aggregation compared with raw TCG at the same dose of TCG. And, a 10 mg/kg dose of raw TCG suspension and a 5 mg/kg dose of TCG-SM had a similar area under the inhibitory curve (907.0%±408.8% and 907.8%±200.5%·hours, respectively) for antiplatelet activity. Conclusion: These results suggest that the developed TCG-SM could be successfully used as an efficient method to achieve the enhanced antiplatelet activity and bioavailability of TCG. Keywords: ticagrelor, SMEDDS, optimization, bioavailability, platelet aggregation, antiplatelet activity
format	article
author	Na YG Byeon JJ Wang M Huh HW Son GH Jeon SH Bang KH Kim SJ Lee HJ Lee HK Cho CW
author_facet	Na YG Byeon JJ Wang M Huh HW Son GH Jeon SH Bang KH Kim SJ Lee HJ Lee HK Cho CW
author_sort	Na YG
title	Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor
title_short	Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor
title_full	Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor
title_fullStr	Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor
title_full_unstemmed	Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor
title_sort	strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/5c9da4c1f51f4a8abf3978d691dd4b4e
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Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor

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