title: Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using Box Behnken design.
abstract: BACKGROUND
  The objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability.
  
  
  METHODS
  The Polymeric lipid hybrid nanoparticle formulation was prepared by the emulsification solvent evaporation method and 3 factor 3 level Box Behnken statistical design was used to optimize and derive a second order polynomial equation and construct contour plots to predict responses. Biodegradable Polycaprolactone, soya lecithin and Poly vinyl alcohol were used to prepare PLHNs. The independent variables selected were lipid to polymer ratio (X1) Concentration of surfactant (X2) Concentration of the drug (X3).
  
  
  RESULTS
  The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of Itraconazole PLHNs. Itraconazole PLHNs revealed nano size (210 ± 1.8 nm) with an entrapment efficiency of 83 ± 0.6% and negative zeta potential of -11.7 mV and also enhance the permeability of itraconazole as the permeability coefficient (Papp) and the absorption enhancement ratio was higher.
  
  
  CONCLUSIONS
  The tunable particle size, surface charge, and favourable encapsulation efficiency with a sustained drug release profile of PLHNs suggesting that it could be promising system envisioned to increase the bioavailability by improving intestinal permeability through lymphatic uptake, M cell of payer's patch or paracellular pathway which was proven by confocal microscopy.
authors.affiliation: Department of Pharmaceutics & Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus, Changa, 388 421, Gujarat, India. balaramgajra.ph@charusat.ac.in.
authors.forename: Balaram
authors.initials: B
authors.lastname: Gajra
authors.affiliation: Department of Pharmaceutics & Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus, Changa, 388 421, Gujarat, India. chintandalwadi17@yahoo.com.
authors.forename: Chintan
authors.initials: C
authors.lastname: Dalwadi
authors.affiliation: Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University (IIT-BHU), Varanasi, 221 005, UP, India. pravi.rs.phe12@iitbhu.ac.in.
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000648:ultrastructure; D017964:Itraconazole / Q000737:chemistry / Q000493:pharmacokinetics*; D008081:Liposomes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
chemical_list: D000935:Antifungal Agents; D008081:Liposomes; D017964:Itraconazole