Thermal Analysis of Freeze-Dried Liposome–Carbohydrate Mixtures with Modulated Temperature Differential Scanning Calorimetry†

Abstract

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.

The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems

“…Early studies have indicated that modulated DSC may be particularly useful for measuring transitions of the dried product in terms of identifying and quantifying the value of T g in complex systems (Kett et al, 1988;Van Winden et al, 1998). …”

“…This is possible because the organism accumulates large amounts of saccharides, usually either sucrose or trehalose (Crowe et al, 1984), and their ability to survive dehydration can be correlated with the concentration of sugar present. Both of these sugars have been investigated as additives to freeze dried protein formulations (Carpenter and Crowe, 1989;Hall et al, 1995) and liposomes (Van Winden et al, 1998).…”

Redispersible Freeze‐dried Quercetin‐loaded Liposomal Formulations Stabilized with Lyoprotectants

“…Thus, in this study we aimed to enhance the physical stability of freeze‐dried liposomes loaded with quercetin using four different saccharides such as glucose, lactose, sucrose, and trehalose. The lyoprotectants were selected based on their different glass transition temperatures, which is known to be crucial for the lyoprotective ability . We evaluated the effect of the addition of the saccharides to the liposomal suspension containing quercetin on the physical stability of the liposomes after the freeze‐drying and rehydration processes.…”

Development and Evaluation of Paclitaxel-Loaded Liposomal Formulations for Targeted Drug Delivery to Breast Cancer

“…In contrast, a change in freezing rate did not affect retention of carboxyfluorescein in EPC containing liposomes. The potential of modulated DSC (MDSC) to study the thermal properties of freeze dried and frozen phospholipid and carbohydrate mixtures has been described [229]. The MDSC measurements of slowly and quickly frozen liposomes showed that the glass transition for quick freezing occurred at lower temperatures than slow freezing.…”