title: Measurement of Shrinkage and Cracking in Lyophilized Amorphous Cakes. Part II: Kinetics.
abstract: OBJECTIVE
  Measurement of the kinetic development of shrinkage and cracking of an amorphous trehalose cake as they take place during lyophilization.
  
  
  METHODS
  A novel technique has been developed which monitors a vial in situ during the freeze-drying cycle. The 2-dimensional degrees of shrinkage and cracking in its top surface are determined quantitatively using a digital camera and evaluated using AxioVision.
  
  
  RESULTS
  Shrinkage and cracking develop largely already during programmed primary drying and are coupled. For trehalose, sucrose and maltose no clear correlation between shrinkage and wg' is found. There is no dependence of cake rim detachment from the vial inner surface on the trehalose concentration. Cake adhesion is therefore likely not the only determining factor for detachment and shrinkage.
  
  
  CONCLUSIONS
  If shrinkage can occur during primary drying, then this relaxes the drying tension produced by desorption of non-frozen water out of the amorphous structure left behind as the sublimation front passes through a volume element, and causes little or no cracking. If shrinkage is restrained, then the drying tension is relaxed by cracking of the brittle cake.
authors: Division of Pharmaceutics, Friedrich Alexander University Erlangen, Cauerstrasse 4, 91058, Erlangen, Germany.
authors: Sabine
authors: S
authors: Ullrich
authors: Stefan
authors: S
authors: Seyferth
authors: Geoffrey
authors: G
authors: Lee
mesh_terms: D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D007700:Kinetics; D008320:Maltose / Q000737:chemistry; D012996:Solutions; D013395:Sucrose / Q000737:chemistry; D013816:Thermodynamics; D014199:Trehalose / Q000737:chemistry*
chemical_list: D005079:Excipients; D012996:Solutions; D013395:Sucrose; D008320:Maltose; D014199:Trehalose
references: Langmuir. 2004 Nov 9;20(23):9885-8
references: 15518466
references: Pharm Res. 2004 Feb;21(2):191-200
references: 15032301
references: AAPS PharmSciTech. 2010 Mar;11(1):73-84
references: 20058107
references: Pharm Dev Technol. 2005;10(1):33-40
references: 15776811
references: J Pharm Sci. 2015 Jan;104(1):155-64
references: 25421825
references: AAPS PharmSciTech. 2011 Mar;12(1):372-8
references: 21347620
references: J Pharm Sci. 2001 Sep;90(9):1345-55
references: 11745787
references: J Pharm Sci. 2010 Jun;99(6):2863-73
references: 19960528