title: Preparation, in-vitro and in-vivo evaluation of spray-dried ternary solid dispersion of biopharmaceutics classification system class II model drug.
abstract: OBJECTIVE
  The objective of this study was to investigate the impact of a novel spray-dried ternary solid dispersion (TSD) on the dissolution rate and bioavailability of a biopharmaceutics classification system (BCS) class II model drug, atorvastatin calcium trihydrate (ATC), and evaluate its in-vitro and in-vivo performance.
  
  
  METHODS
  TSD of ATC was prepared by spray-drying method employing ethanol/water solvent systems. The TSD formulations, composed of hydroxypropyl methylcellulose (HPMC E5) and nicotinamide, were optimized by rotatable central composite design. Physicochemical characterization along with dissolution, stability and pharmacokinetic study of optimized TSD was evaluated.
  
  
  RESULTS
  The optimized TSD was found to be amorphous with spherical shape morphology. It exhibited a fourfold increase in dissolution rate in comparison to ATC, with a considerable enhancement in oral bioavailability (relative bioavailability of 134.11%). Physicochemical characterization and dissolution study of optimized TSD at the end of stability studies clearly indicated that the stability of optimized TSD was due to hydrogen bonding between drug and HPMC E5 and nicotinamide. This bonding remained unaffected even under stressful conditions of high temperature and humidity.
  
  
  CONCLUSIONS
  The TSD exhibits a significant increase in dissolution rate, and for this reason should be useful as an efficacious tool to enhance the bioavailability of BCS class II drug molecule, ATC.
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab, India.
authors.forename: Sharan K
authors.initials: SK
authors.lastname: Paidi
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Jena
authors.forename: Bhupesh K
authors.initials: BK
authors.lastname: Ahuja
authors.forename: Naresh
authors.initials: N
authors.lastname: Devasari
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000493:pharmacokinetics*; D001682:Biological Availability; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions / Q000493:pharmacokinetics*; D005260:Female; D051381:Rats
chemical_list: D004655:Emulsions; D000069059:Atorvastatin
keywords: atorvastatin; bioavailability; nicotinamide; spray-dried; ternary solid dispersion