A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization

Navya Sree Kola Srinivas,1 Ruchi Verma,2 Girish Pai Kulyadi,1 Lalit Kumar1 1Department of Pharmaceutics, 2Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India Abstract: Gefitinib is an anticancer agent which acts by inhib...

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Autores principales:	Kola Srinivas NS, Verma R, Pai Kulyadi G, Kumar L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Gefitinib cancer EGFR tyrosine kinase receptors inhibitor bioavailability Eudragit® RL 100 PVP K 30 PVA BCS Class II QbD DoE Full factorial design. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f33cc91ad291476b93ac0b71fab0d6f6
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spelling	oai:doaj.org-article:f33cc91ad291476b93ac0b71fab0d6f62021-12-02T00:37:18ZA quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization1178-2013https://doaj.org/article/f33cc91ad291476b93ac0b71fab0d6f62016-12-01T00:00:00Zhttps://www.dovepress.com/a-quality-by-design-approach-on-polymeric-nanocarrier-delivery-of-gefi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Navya Sree Kola Srinivas,1 Ruchi Verma,2 Girish Pai Kulyadi,1 Lalit Kumar1 1Department of Pharmaceutics, 2Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India Abstract: Gefitinib is an anticancer agent which acts by inhibiting epidermal growth factor receptor tyrosine kinase receptors. The aim of the present study was to prepare gefitinib nanosuspension. Gefitinib was encapsulated in Eudragit® RL100 and then dispersed in stabilizer solution, polyvinyl alcohol, and polyvinylpyrrolidone K30. Nanosuspension was prepared by using homogenization and ultrasonication techniques. The quality by design approach was also used in the study to understand the effect of critical material attributes (CMAs) and critical processing parameters (CPPs) on critical quality attributes and to improve the quality and safety of formulation. To study the effect of CMAs and CPPs, 23 full factorial design was applied. The particle size, polydispersity index, and zeta potential of the optimized solution were 248.20 nm, 0.391, and -5.62 mV, respectively. Drug content of the optimized nanoformulation was found to be 87.74%±1.19%. Atomic force microscopy studies of the optimized formulation confirmed that the prepared nanoparticles are smooth and spherical in nature. In vitro cytotoxicity studies of the nanosuspension on Vero cell line revealed that the formulation is nontoxic. The gefitinib nanosuspension released 60.03%±4.09% drug over a period of 84 h, whereas standard drug dispersion released only 10.39%±3.37% drug in the same duration. From the pharmacokinetic studies, half-life, Cmax, and Tmax of the drug of an optimized nanosuspension were found to be 8.65±1.99 h, 46,211.04±5,805.97 ng/mL, and 6.67±1.77 h, respectively. A 1.812-fold increase in relative bioavailability of nanosuspension was found, which confirmed that the present formulation is suitable to enhance the oral bioavailability of gefitinib. Keywords: gefitinib, cancer, epidermal growth factor receptor tyrosine kinase receptors inhibitor, bioavailability, Eudragit® RL100, PVP K30, PVA, Biopharmaceutical Classification System class II, QbD, design of experiment, full factorial designKola Srinivas NSVerma RPai Kulyadi GKumar LDove Medical PressarticleGefitinibcancerEGFR tyrosine kinase receptors inhibitorbioavailabilityEudragit® RL 100PVP K 30PVABCS Class IIQbDDoEFull factorial design.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 15-28 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gefitinib cancer EGFR tyrosine kinase receptors inhibitor bioavailability Eudragit® RL 100 PVP K 30 PVA BCS Class II QbD DoE Full factorial design. Medicine (General) R5-920
spellingShingle	Gefitinib cancer EGFR tyrosine kinase receptors inhibitor bioavailability Eudragit® RL 100 PVP K 30 PVA BCS Class II QbD DoE Full factorial design. Medicine (General) R5-920 Kola Srinivas NS Verma R Pai Kulyadi G Kumar L A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization
description	Navya Sree Kola Srinivas,1 Ruchi Verma,2 Girish Pai Kulyadi,1 Lalit Kumar1 1Department of Pharmaceutics, 2Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India Abstract: Gefitinib is an anticancer agent which acts by inhibiting epidermal growth factor receptor tyrosine kinase receptors. The aim of the present study was to prepare gefitinib nanosuspension. Gefitinib was encapsulated in Eudragit® RL100 and then dispersed in stabilizer solution, polyvinyl alcohol, and polyvinylpyrrolidone K30. Nanosuspension was prepared by using homogenization and ultrasonication techniques. The quality by design approach was also used in the study to understand the effect of critical material attributes (CMAs) and critical processing parameters (CPPs) on critical quality attributes and to improve the quality and safety of formulation. To study the effect of CMAs and CPPs, 23 full factorial design was applied. The particle size, polydispersity index, and zeta potential of the optimized solution were 248.20 nm, 0.391, and -5.62 mV, respectively. Drug content of the optimized nanoformulation was found to be 87.74%±1.19%. Atomic force microscopy studies of the optimized formulation confirmed that the prepared nanoparticles are smooth and spherical in nature. In vitro cytotoxicity studies of the nanosuspension on Vero cell line revealed that the formulation is nontoxic. The gefitinib nanosuspension released 60.03%±4.09% drug over a period of 84 h, whereas standard drug dispersion released only 10.39%±3.37% drug in the same duration. From the pharmacokinetic studies, half-life, Cmax, and Tmax of the drug of an optimized nanosuspension were found to be 8.65±1.99 h, 46,211.04±5,805.97 ng/mL, and 6.67±1.77 h, respectively. A 1.812-fold increase in relative bioavailability of nanosuspension was found, which confirmed that the present formulation is suitable to enhance the oral bioavailability of gefitinib. Keywords: gefitinib, cancer, epidermal growth factor receptor tyrosine kinase receptors inhibitor, bioavailability, Eudragit® RL100, PVP K30, PVA, Biopharmaceutical Classification System class II, QbD, design of experiment, full factorial design
format	article
author	Kola Srinivas NS Verma R Pai Kulyadi G Kumar L
author_facet	Kola Srinivas NS Verma R Pai Kulyadi G Kumar L
author_sort	Kola Srinivas NS
title	A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization
title_short	A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization
title_full	A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization
title_fullStr	A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization
title_full_unstemmed	A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization
title_sort	quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/f33cc91ad291476b93ac0b71fab0d6f6
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A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization

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