title: Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on Stability II: stability of a vaccine.
abstract: OBJECTIVE
  To investigate the impact of drying method on the storage stability of dried vaccine formulations.
  
  
  METHODS
  A sucrose-based formulation of a live attenuated virus vaccine of a parainfluenza strain, with and without surfactant, was dried from by different methods; freeze drying, spray drying and foam drying. Dried powders were characterized by differential scanning calorimetry, specific surface area (SSA) analysis and by electron spectroscopy for chemical analysis (ESCA) to evaluate vaccine surface coverage in the dried formulations. Dried formulations were subjected to storage stability studies at 4, 25 and 37 degrees C. The vaccine was assayed initially and at different time points to measure virus-cell infectivity, and the degradation rate constant of the vaccine in different dried preparations was determined.
  
  
  RESULTS
  SSA was highest with the spray dried preparation without surfactant (approximately 2.8 m(2)/g) and lowest in the foam dried preparations (with or without surfactant) (approximately 0.1 m(2)/g). Vaccine surface coverage was estimated based on ESCA measurements of nitrogen content. It was predicted to be highest in the spray dried preparation without surfactant and lowest in the foam with surfactant. Stability studies conducted at 25 degrees C and 37 degrees C showed that the vaccine was most stable in the foam dried preparation with surfactant and least stable in spray dried preparations without surfactant and in all freeze dried preparations regardless of the presence of surfactant. Addition of surfactant did lower the SSA and vaccine surface coverage in freeze dried preparations but still did not improve storage stability.
  
  
  CONCLUSIONS
  In drying methods that did not involve a freezing step, good storage stability of Medi 534 vaccine in the dried form was found with low SSA and low vaccine surface accumulation, both of which integrate into low fraction of vaccine at the surface. Ice appears to be a major destabilizing influence.
authors: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors: Ahmad M
authors: AM
authors: Abdul-Fattah
authors: Vu
authors: V
authors: Truong-Le
authors: Luisa
authors: L
authors: Yee
authors: Emilie
authors: E
authors: Pan
authors: Yi
authors: Y
authors: Ao
authors: Devendra S
authors: DS
authors: Kalonia
authors: Michael J
authors: MJ
authors: Pikal
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002522:Chlorocebus aethiops; D003460:Crystallization; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D003890:Desiccation / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D004583:Electrons; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D007252:Influenza Vaccines / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D010224:Parainfluenza Virus 3, Human / Q000276:immunology* / Q000472:pathogenicity; D020442:Poloxamer / Q000737:chemistry; D011208:Powders; D013057:Spectrum Analysis / Q000379:methods; D013395:Sucrose / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D044366:Transition Temperature; D014613:Vaccines, Attenuated / Q000737:chemistry; D014709:Vero Cells; D014867:Water / Q000737:chemistry
chemical_list: D005079:Excipients; D007252:Influenza Vaccines; D011208:Powders; D013501:Surface-Active Agents; D014613:Vaccines, Attenuated; D014867:Water; D020442:Poloxamer; D013395:Sucrose