Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride

Marianne Joseph Naguib,1 Ibrahim Elsayed,1,2 Mahmoud Hassan Teaima1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, College of Pharmacy and Thumbay Research Institute for Precision Medicine, Gulf Medic...

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Autores principales:	Naguib MJ, Elsayed I, Teaima MH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	ivabradine oral transdermal central composite lyophilized extensive first pass Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5d8399936e0446ab869b202c90aa4dba
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spelling	oai:doaj.org-article:5d8399936e0446ab869b202c90aa4dba2021-12-02T15:39:46ZSimultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride1178-2013https://doaj.org/article/5d8399936e0446ab869b202c90aa4dba2021-04-01T00:00:00Zhttps://www.dovepress.com/simultaneous-optimization-of-oral-and-transdermal-nanovesicles-for-bio-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Marianne Joseph Naguib,1 Ibrahim Elsayed,1,2 Mahmoud Hassan Teaima1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, College of Pharmacy and Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Marianne Joseph NaguibDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, EgyptEmail marian.naguib@pharma.cu.edu.egPurpose: Ivabradine hydrochloride is selective pacemaker current (If) ion channel inhibitor used in case of chronic heart failure (CHF) with superior efficacy and lower side effects than most β-blockers. However, the drug suffers from low bioavailability (≈40%) due to extensive first-pass metabolism. Hence, this work aims to formulate nanovesicular platforms to enhance their bioavailability both orally and transdermally.Materials and Methods: A central composite face-centered design was employed to formulate the nanovesicles, both phosphatidylcholine: drug ratio and percentage of pluronic F68 were used as independent variables. The nine developed formulae were characterized in terms of vesicle size (nm), polydispersity index, zeta potential (mV), entrapment efficiency (%). Decreasing vesicle size, increasing negative value of the zeta potential, and increasing entrapment efficiency were the chosen constraints to optimize the engineered nanovesicles. The candidate formula was subjected to further investigation including lyophilization, loading into carbopol gel, in vitro release, imaging with a transmission electron microscope, histopathological examination, in vitro cytotoxicity study and in vivo pharmacokinetics.Results: The optimized nanovesicular formula was composed of lipid: drug ratio of 3.91:1 and 100% pluronic as a stabilizer. It has particle size, zeta potential and entrapment efficiency of 337.6 nm, − 40.5 mV and 30.5, respectively. It was then lyophilized in the presence of 5% trehalose as a cryoprotectant, dispersed in 0.5% carbopol to develop the transdermal gel. The two different forms of the candidate formula (lyophilized and gel form) displayed sustained drug release in comparison to drug solution. The histopathological and cytotoxicity studies showed that the optimized formula was safe and highly biocompatible. The pharmacokinetics parameters measured declared a higher Cmax and half-life of both formulae in comparison to market product (Procoralan®) with a 2.54- and 1.85-folds increase in bioavailability, respectively.Conclusion: Hence, the developed nanovesicles can be reported as the first nanoplatforms to be used for simultaneous ivabradine delivery by both oral and topical routes with enhanced oral and transdermal drug delivery. The developed nanoplatforms hence can be further used to formulate other drugs that suffer from low bioavailability due to extensive first-pass metabolism.Keywords: ivabradine, oral, transdermal, central composite, lyophilized, extensive first passNaguib MJElsayed ITeaima MHDove Medical Pressarticleivabradineoraltransdermalcentral compositelyophilizedextensive first passMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 2917-2931 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ivabradine oral transdermal central composite lyophilized extensive first pass Medicine (General) R5-920
spellingShingle	ivabradine oral transdermal central composite lyophilized extensive first pass Medicine (General) R5-920 Naguib MJ Elsayed I Teaima MH Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride
description	Marianne Joseph Naguib,1 Ibrahim Elsayed,1,2 Mahmoud Hassan Teaima1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, College of Pharmacy and Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Marianne Joseph NaguibDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, EgyptEmail marian.naguib@pharma.cu.edu.egPurpose: Ivabradine hydrochloride is selective pacemaker current (If) ion channel inhibitor used in case of chronic heart failure (CHF) with superior efficacy and lower side effects than most β-blockers. However, the drug suffers from low bioavailability (≈40%) due to extensive first-pass metabolism. Hence, this work aims to formulate nanovesicular platforms to enhance their bioavailability both orally and transdermally.Materials and Methods: A central composite face-centered design was employed to formulate the nanovesicles, both phosphatidylcholine: drug ratio and percentage of pluronic F68 were used as independent variables. The nine developed formulae were characterized in terms of vesicle size (nm), polydispersity index, zeta potential (mV), entrapment efficiency (%). Decreasing vesicle size, increasing negative value of the zeta potential, and increasing entrapment efficiency were the chosen constraints to optimize the engineered nanovesicles. The candidate formula was subjected to further investigation including lyophilization, loading into carbopol gel, in vitro release, imaging with a transmission electron microscope, histopathological examination, in vitro cytotoxicity study and in vivo pharmacokinetics.Results: The optimized nanovesicular formula was composed of lipid: drug ratio of 3.91:1 and 100% pluronic as a stabilizer. It has particle size, zeta potential and entrapment efficiency of 337.6 nm, − 40.5 mV and 30.5, respectively. It was then lyophilized in the presence of 5% trehalose as a cryoprotectant, dispersed in 0.5% carbopol to develop the transdermal gel. The two different forms of the candidate formula (lyophilized and gel form) displayed sustained drug release in comparison to drug solution. The histopathological and cytotoxicity studies showed that the optimized formula was safe and highly biocompatible. The pharmacokinetics parameters measured declared a higher Cmax and half-life of both formulae in comparison to market product (Procoralan®) with a 2.54- and 1.85-folds increase in bioavailability, respectively.Conclusion: Hence, the developed nanovesicles can be reported as the first nanoplatforms to be used for simultaneous ivabradine delivery by both oral and topical routes with enhanced oral and transdermal drug delivery. The developed nanoplatforms hence can be further used to formulate other drugs that suffer from low bioavailability due to extensive first-pass metabolism.Keywords: ivabradine, oral, transdermal, central composite, lyophilized, extensive first pass
format	article
author	Naguib MJ Elsayed I Teaima MH
author_facet	Naguib MJ Elsayed I Teaima MH
author_sort	Naguib MJ
title	Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride
title_short	Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride
title_full	Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride
title_fullStr	Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride
title_full_unstemmed	Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride
title_sort	simultaneous optimization of oral and transdermal nanovesicles for bioavailability enhancement of ivabradine hydrochloride
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/5d8399936e0446ab869b202c90aa4dba
work_keys_str_mv	AT naguibmj simultaneousoptimizationoforalandtransdermalnanovesiclesforbioavailabilityenhancementofivabradinehydrochloride AT elsayedi simultaneousoptimizationoforalandtransdermalnanovesiclesforbioavailabilityenhancementofivabradinehydrochloride AT teaimamh simultaneousoptimizationoforalandtransdermalnanovesiclesforbioavailabilityenhancementofivabradinehydrochloride
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Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride

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