title: Solubility advantage from amorphous etoricoxib solid dispersions.
abstract: OBJECTIVE
  This study aimed to evaluate kinetic solubility advantage of amorphous etoricoxib solid dispersions prepared with three water soluble polymers and correlate it with solid state and supersaturated drug solution stabilization potential of these polymers.
  
  
  METHODS
  Amorphous solid dispersions (ASDs) of etoricoxib were prepared with polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and hydroxyethyl cellulose (HEC) at 70:30w/w ratio and characterized for glass transition temperature (Tg), miscibility and intermolecular interactions. Kinetic solubility profiles of amorphous etoricoxib and its ASDs were determined in water at 37 °C. Solid-state stability was assessed by enthalpy relaxation studies at a common degree of undercooling of around 19.0 °C at 0% RH. Recrystallization behavior of supersaturated drug solution was evaluated in the absence and presence of pre-dissolved polymer at 37 °C.
  
  
  RESULTS
  Amorphous etoricoxib exhibited rapid solid-to-solid transition to yield a solubility advantage of merely 1.5-fold in water. Among the ASDs, etoricoxib-PVP dispersion exhibited maximal "peak" (2-fold) and "plateau" (1.8-fold) solubility enhancement, while etoricoxib-PVA dispersion could only sustain the "peak" solubility achieved by amorphous etoricoxib. In contrast, etoricoxib-HEC dispersion displayed no solubility advantage. The rank order for solid state and supersaturated solution stabilization followed a similar trend of amorphous etoricoxib < HEC < PVA < PVP.
  
  
  CONCLUSIONS
  Dissolution behavior of ASDs is influenced by concomitantly occurring solid phase changes, thus understanding these processes independently can enable assessment of the predominant route of drug crystallization and stabilization by the polymer.
authors.affiliation: Department of Pharmaceutical Technology (Formulations) and.
authors.forename: Prateek
authors.initials: P
authors.lastname: Dani
authors.forename: Vibha
authors.initials: V
authors.lastname: Puri
authors.forename: A K
authors.initials: AK
authors.lastname: Bansal
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D000077613:Etoricoxib; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013450:Sulfones / Q000008:administration & dosage* / Q000737:chemistry; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D004337:Drug Carriers; D011108:Polymers; D011725:Pyridines; D013450:Sulfones; D011142:Polyvinyl Alcohol; D002482:Cellulose; C002283:hydroxyethylcellulose; D011205:Povidone; D000077613:Etoricoxib