Anna-Kaisa Koskinen1, Sara J Fraser-Miller2, Johan P Bøtker3, Ville P Heljo4, Jonathan E Barnsley5, Keith C Gordon5, Clare J Strachan2, Anne M Juppo2. 1. Formulation and Industrial Pharmacy, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00014, Helsinki, Finland. anna-kaisa.koskinen@helsinki.fi. 2. Formulation and Industrial Pharmacy, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00014, Helsinki, Finland. 3. Department of Pharmacy, Faculty of Health and Medicinal Sciences, University of Copenhagen, Copenhagen, Denmark. 4. Formulation Research Injectables, Protein Engineering, Novo Nordisk A/S, Måløv, Denmark. 5. Department of Chemistry, University of Otago, Dunedin, New Zealand.
Abstract
PURPOSE: 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.
PURPOSE: 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: Ville Petteri Heljo; Antti Nordberg; Mikko Tenho; Tommi Virtanen; Kirsi Jouppila; Jarno Salonen; Sirkka Liisa Maunu; Anne Mari Juppo Journal: Pharm Res Date: 2011-12-28 Impact factor: 4.200