title: Statistical modeling, optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment.
abstract: OBJECTIVE
  Lopinavir (LPV), an antiretroviral protease inhibitor shows poor bioavailability because of poor aqueous solubility and extensive hepatic first-pass metabolism. The aim of the present work was to investigate the potential of the solid self-nanoemulsifying drug delivery system (S-SNEDDS) in improving dissolution rate and oral bioavailability of LPV.
  
  
  METHODS
  Liquid SNEDDS (L-SNEDDS) of LPV were prepared using Capmul MCM C8, Cremophor RH 40 and propylene glycol and their amounts were optimized by Scheffe's mixture design. L-SNEDDS formulations were evaluated for different physicochemical and in vitro drug release parameters. S-SNEDDS were prepared by adsorbing L-SNEDDS on Neusilin US2 and characterized for solid-state properties. In vivo bioavailability of S-SNEDDS, marketed Lopinavir + Ritonavir (LPV/RTV) formulation and pure LPV was studied in Wistar rats. Stability study of S-SNEDDS was performed as per ICH guidelines.
  
  
  CONCLUSIONS
  Optimized L-SNEDDS obtained by Scheffe design had drug loading 160 ± 1.15 mg, globule size 32.9 ± 1.45 nm and drug release >95% within 15 min. Solid state studies suggested the transformation of the crystalline drug to amorphous drug. The size and zeta potential of globules obtained on dilution S-SNEDDS remained similar to L-SNEEDS. In vivo bioavailability study revealed that S-SNEDDS has 2.97 and 1.54-folds higher bioavailability than pure LPV and LPV/RTV formulation, respectively. The optimized S-SNEDDS was found to be stable and had a shelf life of 2.85 years.
  
  
  CONCLUSIONS
  The significant increase in drug dissolution and bioavailability by prepared SNEDDS suggest that the developed S-SNEDDS is a useful solid platform for improving oral bioavailability of poorly soluble LPV.
authors.affiliation: a Department of Pharmaceutics , K. B. Institute of Pharmaceutical Education and Research , Gandhinagar , Gujarat , India.
authors.forename: Grishma
authors.initials: G
authors.lastname: Patel
authors.affiliation: a Department of Pharmaceutics , K. B. Institute of Pharmaceutical Education and Research , Gandhinagar , Gujarat , India.
authors.forename: Pragna
authors.initials: P
authors.lastname: Shelat
authors.affiliation: a Department of Pharmaceutics , K. B. Institute of Pharmaceutical Education and Research , Gandhinagar , Gujarat , India.
authors.forename: Anita
authors.initials: A
authors.lastname: Lalwani
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry*; D005260:Female; D061466:Lopinavir / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D061466:Lopinavir; C022131:cremophor; D011092:Polyethylene Glycols
keywords: Bioavailability; Scheffe design; dissolution; lopinavir; solid carriers; solid self-nanoemulsifying drug delivery system