title: Inclusion complex of erlotinib with sulfobutyl ether-β-cyclodextrin: Preparation, characterization, in silico, in vitro and in vivo evaluation.
abstract: The aim of the study was to investigate the impact of erlotinib sulfobutyl ether beta-cyclodextrin complex (ERL-SBE-β-CD) on ERL dissolution rate and oral bioavailability. Preliminary comparative phase solubility study indicated ERL exhibited maximum solubility in SBE-β-CD solution. Optimal experimental design confirmed freeze drying of SBE-β-CD:ERL in 1:1.05 molar ratio as the optimum method. Differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), proton nuclear magnetic resonance ((1)H NMR) and two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY NMR) confirmed the inclusion complexation. The in silico computational study, employed to analyze the comparative interactions of ERL with SBE-β-CD and β-CD, indicated ease of ERL-SBE-β-CD complexation. In vitro dissolution and in vivo bioavailability studies further confirmed the ERL-SBE-β-CD as a valuable approach to enhance ERL oral bioavailability with 3.6-fold increase in relative oral bioavailability with higher Cmax (134.29 ± 36.51 vs. 42.36 ± 1.75 μg/ml) and AUC0-∞ (2103.47 ± 156.75 vs.580.43 ± 71.91 μg/ml h) over the free drug. The complex exhibited 3.2-fold increase in Cmax with 5.4-fold decrease in Tmax (0.5 ± 0.2 vs. 2.7 ± 0.8h) in comparison to pure ERL. Thus, ERL-SBE-β-CD complexation exhibits a potential to enhance oral bioavailability of ERL leading to reduce dose and dose-related side effects.
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India.
authors.forename: Naresh
authors.initials: N
authors.lastname: Devasari
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India.
authors.forename: Chander Parkash
authors.initials: CP
authors.lastname: Dora
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India.
authors.forename: Charan
authors.initials: C
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India.
authors.forename: Sharan Reddy
authors.initials: SR
authors.lastname: Paidi
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160067, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160067, India.
authors.forename: Masilamani Elizabeth
authors.initials: ME
authors.lastname: Sobhia
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India. Electronic address: sarasija_s@hotmail.com.
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002236:Carbohydrate Conformation; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D000069347:Erlotinib Hydrochloride
keywords: Ammonium acetate (PubChem CID: 517165); Atorvastatin (PubChem CID: 60823); Cyclodextrin; Erlotinib; Erlotinib hydrocholide (PubChem CID: 176871); Pancreatic cancer; Solubility enhancement; Sulfobutyl ether β-cyclodextrin; Tyrosine kinase inhibitor; α-Cyclodextrin (PubChem CID: 444913); β-Cyclodextrin (PubChem CID: 444041); γ-Cyclodextrin (PubChem CID: 86575)