title: Bioavailability enhancement and pharmacokinetic profile of an anticancer drug ibrutinib by self-nanoemulsifying drug delivery system.
abstract: OBJECTIVE
  The current studies were undertaken to enhance dissolution and bioavailability/pharmacokinetic profile of a newly approved anticancer drug ibrutinib (IBR) via encapsulation of drug into self-nanoemulsifying drug delivery system (SNEDDS).
  
  
  METHODS
  Various SNEDDS formulations of IBR were developed by aqueous phase titration method using Capryol-PGMC (oil phase), Tween-20 (surfactant), Carbitol (cosurfactant) and water (aqueous phase). Developed SNEDDS of IBR was evaluated in vitro for various physicochemical properties and drug release profile.
  
  
  RESULTS
  Based on lowest droplet size (28.7 ± 3.2 nm), least polydispersity (0.123), optimal values of zeta potential (-32.8 mV) and refractive index (1.336), highest % transmittance (98.7 ± 0.2%), highest drug release profile via dialysis membrane (98.9 ± 8.2% after 48 h) and the presence of lowest concentration of Capryol-PGMC (12% w/w), SNEDDS I1 was selected for in-vivo pharmacokinetic/bioavailability studies in female Wistar rats. In-vivo pharmacokinetic studies in rats showed that optimized SNEDDS I1 controlled the absorption of IBR compared with IBR suspension. The bioavailability of IBR from optimized SNEDDS I1 was enhanced around 2.64 times in comparison with IBR suspension.
  
  
  CONCLUSIONS
  These results indicated the potential of developed SNEDDS as an alternative drug delivery system for IBR to enhance its bioavailability and anticancer efficacy.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.|Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
authors.forename: Faiyaz
authors.initials: F
authors.lastname: Shakeel
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.|Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Iqbal
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.|Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Essam
authors.initials: E
authors.lastname: Ezzeldin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005260:Female; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D010880:Piperidines; D011108:Polymers / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004655:Emulsions; D005026:Ethylene Glycols; D010880:Piperidines; D011108:Polymers; D011136:Polysorbates; D011409:Propylene Glycols; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D013501:Surface-Active Agents; C584816:capryol propylene glycol monocaprylate; D014867:Water; C551803:ibrutinib; C010111:carbitol; D000225:Adenine
keywords: bioavailability; cancer; drug release; ibrutinib; pharmacokinetic