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®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, 23full 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.
authors.affiliation: Department of Pharmaceutics.
authors.forename: Navya Sree
authors.initials: NS
authors.lastname: Kola Srinivas
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Verma
authors.affiliation: Department of Pharmaceutics.
authors.forename: Girish
authors.initials: G
authors.lastname: Pai Kulyadi
authors.affiliation: Department of Pharmaceutics.
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001682:Biological Availability; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D000077156:Gefitinib; D006207:Half-Life; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D011799:Quinazolines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D017208:Rats, Wistar; D013535:Suspensions / Q000737:chemistry; D014709:Vero Cells / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D011109:Polymethacrylic Acids; D011799:Quinazolines; D013535:Suspensions; C038300:methylmethacrylate-methacrylic acid copolymer; D011142:Polyvinyl Alcohol; D011205:Povidone; D000077156:Gefitinib
keywords: Biopharmaceutical Classification System class II; Eudragit® RL100; PVA; PVP K30; QbD; bioavailability; cancer; design of experiment; epidermal growth factor receptor tyrosine kinase receptors inhibitor; full factorial design; gefitinib