Thermal analysis of freeze-dried liposome-carbohydrate mixtures with modulated temperature differential scanning calorimetry.
In this study we investigated the use of modulated temperature differential scanning calorimetry (MTDSC) for the detection of the glass transition temperature (Tg) in freeze-dried cakes of lyoprotected liposomes and for the analysis of frozen carbohydrate solutions. The glass transition appeared in the reversing heat flow, whereas the bilayer melting endotherm was observed in the nonreversing heat flow. This enabled the detection of Tg even in samples were the glass and bilayer transition overlapped. In addition, relaxation processes occurring in nonannealed freeze-dried carbohydrate-liposome mixtures, which hinder the determination of Tg with conventional DSC, were also separated from the heat capacity related heat flow. Analysis of frozen carbohydrate solutions with MTDSC facilitated the identification of the glass transition, devitrification peak, and "softening" transition, which could help to further optimize freeze-drying conditions by rationale. Sampling and selection of experimental parameters are discussed for the special case of porous, freeze-dried cakes.
van Winden
E C
EC
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands.
Talsma
H
H
Crommelin
D J
DJ
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry*; D004337:Drug Carriers; D005612:Freeze Drying; D005947:Glucose / Q000737:chemistry; D008051:Lipid Bilayers; D008081:Liposomes / Q000737:chemistry*; D013696:Temperature
D004187:Disaccharides; D004337:Drug Carriers; D008051:Lipid Bilayers; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; D005947:Glucose