title: Defining the design space for freeze-dried orodispersible tablets with meloxicam.
abstract: OBJECTIVE
  This work focused on simultaneously investigating formulation variables and freeze-drying parameters when preparing orodispersible tablets with meloxicam (Mel), by a Quality by Design (QbD) approach.
  
  
  METHODS
  Methylcellulose (MC) was selected as a matrix forming agent and mannitol (Man) as cryoprotectant, both at two concentration levels. The freezing regime was also varied between fast and shelf-ramped, to find out how it affects the final products. The tablet formulations were characterized for their disintegration time, wetting properties, mechanical properties, morphology and in vitro dissolution. Response Surface Modeling completed the statistical analysis that assessed the effects of independent variables on the responses.
  
  
  RESULTS
  All the responses showed good fitting to the chosen model. The increase in MC content determined a positive effect on disintegration time, wetting time, mechanical strength and a negative effect on Mel dissolution. High levels of Man-determined brittle products with low-absorption capacity and fast Mel dissolution. The freezing rate had an important effect on the structure of tablets: fast freezing determined slightly thicker pore walls with smooth surfaces, while shelf-ramped freezing led to a multiple-layer structure with increased hardness. Still, shelf-ramped freezing yielded higher Mel release, due to physical changes of the active substance during the freeze-drying process.
  
  
  CONCLUSIONS
  From the generated design space, an optimal formulation was obtained and the results validated the experimental design. The QbD approach was an efficient manner of understanding formulation and process parameters at the freeze-dried orodispersible tablets preparation.
authors.affiliation: a Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy , University of Medicine and Pharmacy Iuliu Hatieganu , Cluj-Napoca , Romania ;
authors.forename: Sonia
authors.initials: S
authors.lastname: Iurian
authors.affiliation: a Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy , University of Medicine and Pharmacy Iuliu Hatieganu , Cluj-Napoca , Romania ;
authors.forename: Ioan
authors.initials: I
authors.lastname: Tomuta
authors.affiliation: b Department of Dermopharmacy and Cosmetics , University of Medicine and Pharmacy Iuliu Hatieganu , Cluj-Napoca , Romania ;
authors.forename: Cătălina
authors.initials: C
authors.lastname: Bogdan
authors.affiliation: c Department of Drug Analysis , University of Medicine and Pharmacy Iuliu Hatieganu , Cluj-Napoca , Romania ;
authors.forename: Lucia
authors.initials: L
authors.lastname: Rus
authors.affiliation: a Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy , University of Medicine and Pharmacy Iuliu Hatieganu , Cluj-Napoca , Romania ;
authors.forename: Timea
authors.initials: T
authors.lastname: Tokes
authors.affiliation: d Electron Microscopy Center, Babeş-Bolyai University , Cluj-Napoca , Romania.
authors.forename: Lucian
authors.initials: L
authors.lastname: Barbu-Tudoran
authors.affiliation: a Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy , University of Medicine and Pharmacy Iuliu Hatieganu , Cluj-Napoca , Romania ;
authors.forename: Marcela
authors.initials: M
authors.lastname: Achim
authors.affiliation: a Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy , University of Medicine and Pharmacy Iuliu Hatieganu , Cluj-Napoca , Romania ;
authors.forename: Mirela
authors.initials: M
authors.lastname: Moldovan
authors.affiliation: a Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy , University of Medicine and Pharmacy Iuliu Hatieganu , Cluj-Napoca , Romania ;
authors.forename: Sorin
authors.initials: S
authors.lastname: Leucuta
keywords: Design of experiments; design space; freezing rate; meloxicam; oral lyophilisates; quality by design