A quality by design approach on polymeric nanocarrier delivery of gefitinib

Formulation, in vitro, and in vivo characterization

Navya Sree Kola Srinivas, Ruchi Verma, Girish Pai Kulyadi, Lalit Kumar

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 Tmaxof 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.

Original languageEnglish
Pages (from-to)15-28
Number of pages14
JournalInternational Journal of Nanomedicine
Volume12
DOIs
Publication statusPublished - 2017

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Strategic materials
Pharmacokinetics
Polyvinyl alcohols
Polydispersity
Zeta potential
Cytotoxicity
Processing
Pharmaceutical Preparations
Atomic force microscopy
Particle size
Cells
Biological Availability
Nanoparticles
Polyvinyl Alcohol
Povidone
Vero Cells
Atomic Force Microscopy
Receptor Protein-Tyrosine Kinases
Particle Size
Epidermal Growth Factor Receptor

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Drug Discovery
  • Organic Chemistry

Cite this

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title = "A quality by design approach on polymeric nanocarrier delivery of gefitinib: Formulation, in vitro, and in vivo characterization",
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{\circledR} 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 Tmaxof 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.",
author = "Srinivas, {Navya Sree Kola} and Ruchi Verma and Kulyadi, {Girish Pai} and Lalit Kumar",
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AU - Kumar, Lalit

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AB - 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 Tmaxof 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.

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