title: Elucidation of Compression-Induced Surface Crystallization in Amorphous Tablets Using Sum Frequency Generation (SFG) Microscopy.
abstract: To investigate the effect of compression on the crystallization behavior in amorphous tablets using sum frequency generation (SFG) microscopy imaging and more established analytical methods.
  
  
  
  Tablets containing neat amorphous griseofulvin with/without excipients (silica, hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC) and polyethylene glycol (PEG)) were prepared. They were analyzed upon preparation and storage using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM) and SFG microscopy.
  
  
  
  Compression-induced crystallization occurred predominantly on the surface of the neat amorphous griseofulvin tablets, with minimal crystallinity being detected in the core of the tablets. The presence of various types of excipients was not able to mitigate the compression-induced surface crystallization of the amorphous griseofulvin tablets. However, the excipients affected the crystallization rate of amorphous griseofulvin in the core of the tablet upon compression and storage.
  
  
  
  SFG microscopy can be used in combination with ATR-FTIR spectroscopy and SEM to understand the crystallization behaviour of amorphous tablets upon compression and storage. When selecting excipients for amorphous formulations, it is important to consider the effect of the excipients on the physical stability of the amorphous formulations.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.|Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Pei T
authors.initials: PT
authors.lastname: Mah
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Dunja
authors.initials: D
authors.lastname: Novakovic
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Saarinen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Stijn
authors.initials: S
authors.lastname: Van Landeghem
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.affiliation: Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.|Department of Chemistry and Bioengineering, Faculty of Natural Sciences, Tampere University of Technology, Tampere, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
authors.affiliation: Biomedicum Imaging Unit, Department of Anatomy, Medicum, Faculty of Medicine, FIN-00014 University of Helsinki, Haartmaninkatu 8, P.O. Box 63, Helsinki, Finland. antti.isomaki@helsinki.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Isomäki
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
mesh_terms: D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D005079:Excipients / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry; D011312:Pressure; D012822:Silicon Dioxide / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013607:Tablets / Q000737:chemistry*
chemical_list: D005079:Excipients; D013607:Tablets; D006118:Griseofulvin; D011092:Polyethylene Glycols; C048331:hydroxypropylmethylcellulose acetate succinate; D012822:Silicon Dioxide; D002482:Cellulose; D008747:Methylcellulose; C109691:microcrystalline cellulose
keywords: amorphous; attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy; compression; crystallization; griseofulvin; scanning electron microscopy (SEM); sum frequency generation (SFG) microscopy