title: The secondary drying and the fate of organic solvents for spray dried dispersion drug product.
abstract: OBJECTIVE
  To understand the mechanisms of secondary drying of spray-dried dispersion (SDD) drug product and establish a model to describe the fate of organic solvents in such a product.
  
  
  METHODS
  The experimental approach includes characterization of the SDD particles, drying studies of SDD using an integrated weighing balance and mass spectrometer, and the subsequent generation of the drying curve. The theoretical approach includes the establishment of a Fickian diffusion model.
  
  
  RESULTS
  The kinetics of solvent removal during secondary drying from the lab scale to a bench scale follows Fickian diffusion model. Excellent agreement is obtained between the experimental data and the prediction from the modeling.
  
  
  CONCLUSIONS
  The diffusion process is dependent upon temperature. The key to a successful scale up of the secondary drying is to control the drying temperature. The fate of primary solvents including methanol and acetone, and their potential impurity such as benzene can be described by the Fickian diffusion model. A mathematical relationship based upon the ratio of diffusion coefficient was established to predict the benzene concentration from the fate of the primary solvent during the secondary drying process.
authors.affiliation: Drug Product Science & Technology, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, New Jersey, 08903, USA, daniel.hsieh@bms.com.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Hsieh
authors.forename: Hongfei
authors.initials: H
authors.lastname: Yue
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nicholson
authors.forename: Daniel
authors.initials: D
authors.lastname: Roberts
authors.forename: Richard
authors.initials: R
authors.lastname: Schild
authors.forename: John F
authors.initials: JF
authors.lastname: Gamble
authors.forename: Mark
authors.initials: M
authors.lastname: Lindrud
mesh_terms: D000096:Acetone / Q000302:isolation & purification*; D003890:Desiccation / Q000379:methods*; D004058:Diffusion; D004355:Drug Stability; D007700:Kinetics; D000432:Methanol / Q000302:isolation & purification*; D008956:Models, Chemical; D012997:Solvents / Q000302:isolation & purification*; D013696:Temperature
chemical_list: D012997:Solvents; D000096:Acetone; D000432:Methanol