title: Design of a novel type IV lipid-based delivery system for improved delivery of drugs with low partition coefficient.
abstract: BACKGROUND
  The physicochemical properties of drugs such as partition coefficient play a major role in the development of lipid-based drug delivery systems. The major obstacle lies in encapsulation of a drug with low partition coefficient into these systems.
  
  
  OBJECTIVE
  The objective of this study was to design and optimize a novel lipid-based delivery system with higher loading, improved pharmacokinetics consequently enhancing the oral bioavailability of drugs with low partition coefficient like valsartan.
  
  
  METHODS
  The optimized formulation consists of Capryol 90, Cremophor RH 40, and Transcutol HP. Pseudo ternary phase diagrams were used to optimize the components and their concentrations in the formulation. Dissolution studies of the selected formulations were compared with plain drug and marketed product at three pH conditions (pH 1.2, 4.5 and 6.8). Pharmacokinetic parameters of optimized formulations were determined in Wistar rats and compared with that of plain drug.
  
  
  CONCLUSIONS
  The optimized formulation with a mean particle size of 50 nm showed significant improvement (p < 0.05) in dissolution rate with pH independence compared to plain drug and marketed product. The in vivo studies in Wistar rats revealed about 2.30- and 1.68-fold increase in the oral bioavailability and Cmax of valsartan from lipid-based formulation compared to plain drug.
  
  
  CONCLUSIONS
  The engineered formulation strategy by type IV lipid-based formulations can be successfully exploited to improve the dissolution rate and oral deliverability of drugs like valsartan.
authors.affiliation: a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India.
authors.forename: Laxmi
authors.initials: L
authors.lastname: Narayana
authors.affiliation: a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Chella
authors.affiliation: a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India.
authors.forename: Nalini R
authors.initials: NR
authors.lastname: Shastri
mesh_terms: D020384:Acidic Glycosphingolipids / Q000737:chemistry*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D005026:Ethylene Glycols / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008297:Male; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D000068756:Valsartan / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D020384:Acidic Glycosphingolipids; D004337:Drug Carriers; D005026:Ethylene Glycols; C037242:Lipid IV; D011108:Polymers; D011409:Propylene Glycols; C584816:capryol propylene glycol monocaprylate; C022131:cremophor; D011092:Polyethylene Glycols; D000068756:Valsartan; C010111:carbitol
keywords: Bioavailability; pH-depended solubility; poorly soluble; self nanoemulsifying delivery