title: Formulation and Pharmacokinetic Evaluation of Polymeric Dispersions Containing Valsartan.
abstract: BACKGROUND
  Valsartan exhibits poor aqueous solubility and dissolution rate limited absorption. The lower solubility in the upper part of gastrointestinal tract (pH-dependant solubility) where its absorption window exists further contributes to the low oral bioavailability of valsartan.
  
  
  OBJECTIVE
  The present work was aimed to improve the in vivo pharmacokinetics of valsartan by preparing amorphous polymeric dispersions using Eudragit E 100 as carrier. Eudragit E 100 is a cationic polymer soluble in gastric fluid up to pH 5.0 and exhibits pH-dependent release. Hence, the dispersions prepared using Eudragit E 100 rapidly dissolves at lower pH presenting drug in molecularly dispersed and soluble form at its absorption site.
  
  
  METHODS
  Polymeric solid dispersions were prepared in different drug-to-carrier ratios. The prepared dispersions were evaluated for drug-carrier interactions, solid-state transitions and drug-release properties with the help of Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and in vitro dissolution studies. The optimized formulation containing valsartan was tested in rats for bioavailability and pharmacokinetic parameters and compared with that of valsartan pure drug.
  
  
  RESULTS
  The results from FTIR studies indicated no interactions between drug and excipients. DSC studies confirmed reduction in crystallinity of drug. The dissolution studies performed in 0.1 N HCl showed significant improvement (p < 0.05) in the dissolution of valsartan. In vivo pharmacokinetic studies showed 199 % relative bioavailability with significant improvement (p < 0.05) in area under the curve compared to valsartan pure drug.
  
  
  CONCLUSIONS
  Eudragit E 100 can be used to improve the dissolution of drugs that show low solubility at lower pH and thereby enhancing the bioavailability.
authors.affiliation: National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, 500037, India.|Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, Andhra Pradesh, 522510, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Chella
authors.affiliation: Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, Andhra Pradesh, 522510, India.|Department of Pharmaceutics, Sri Shivani College of Pharmacy, Warangal, Telangana, 506007, India.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Daravath
authors.affiliation: National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, 500037, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutics, Avanthi Institute of Pharmaceutical Sciences, Gunthapally village, Hayath Nagar, Ranga Reddy (D), Hyderabad, Telangana, 501512, India. tramarao2014@gmail.com.
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Tadikonda
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008297:Male; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D000068756:Valsartan / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D000179:Acrylates; D004337:Drug Carriers; C477020:Eudragit E100; D005079:Excipients; D011108:Polymers; D000068756:Valsartan