title: Physical Stability of Freeze-Dried Isomalt Diastereomer Mixtures.
abstract: OBJECTIVE
  Isomalt is a sugar alcohol used as an excipient in commercially available solid oral dosage forms. The potential of isomalt as a novel freeze-drying excipient was studied in order to increase knowledge of the behavior of isomalt when it is freeze-dried.
  
  
  METHODS
  Isomalt was freeze-dried in four different diastereomer compositions and its physical stability was investigated with differential scanning calorimetry, Fourier-transform infrared and Raman spectroscopy, X-ray powder diffraction, Karl-Fischer titration and thermogravimetric analysis in order to verify the solid state form of isomalt after freeze-drying and observe any changes occurring during storage in three different relative humidity conditions.
  
  
  RESULTS
  Isomalt was successfully transformed into the amorphous form with freeze-drying and three diastereomer combinations remained stable as amorphous during storage; one of the diastereomer compositions showed signs of physical instability when stored in the highest relative humidity condition. The four different crystalline diastereomer mixtures showed specific identifiable solid state properties.
  
  
  CONCLUSIONS
  Isomalt was shown to be a suitable excipient for freeze-drying. Preferably a mixture of the diastereomers should be used, as the mixture containing only one of the isomers showed physical instability. A mixture containing a 1:1 ratio of the two diastereomers showed the best physical stability in the amorphous form.
authors.affiliation: Formulation and Industrial Pharmacy, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00014, Helsinki, Finland. anna-kaisa.koskinen@helsinki.fi.
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Koskinen
authors.affiliation: Formulation and Industrial Pharmacy, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00014, Helsinki, Finland.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Fraser-Miller
authors.affiliation: Department of Pharmacy, Faculty of Health and Medicinal Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Johan P
authors.initials: JP
authors.lastname: Bøtker
authors.affiliation: Formulation Research Injectables, Protein Engineering, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Ville P
authors.initials: VP
authors.lastname: Heljo
authors.affiliation: Department of Chemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Barnsley
authors.affiliation: Department of Chemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Keith C
authors.initials: KC
authors.lastname: Gordon
authors.affiliation: Formulation and Industrial Pharmacy, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00014, Helsinki, Finland.
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
authors.affiliation: Formulation and Industrial Pharmacy, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00014, Helsinki, Finland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Juppo
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004187:Disaccharides / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying / Q000379:methods; D006813:Humidity; D011208:Powders / Q000737:chemistry; D012995:Solubility; D013402:Sugar Alcohols / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004187:Disaccharides; D005079:Excipients; D011208:Powders; D013402:Sugar Alcohols; C016640:Palatinit
keywords: amorphous; diastereomer; freeze-drying; isomalt; physical stability