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DSC. As reported in the literature, Tg' does not significantly change with concentration because the composition of the maximally freeze-concentrated solute is
independent of the initial concentration (9). For this reason, only the 5% (w/v) solution was investigated by DSC. At first,
the sample solution was scanned with a 10 °C/min heating rate to roughly detect the temperature range of Tg'. A fast heating rate increases sensitivity, but can also impair representativeness of the measurement by shifting Tg' to higher temperatures (9). To obtain the true result, additional heating rates of 3 and 1 °C/min were applied. Results
are summarised in Table I, where the Tg' onset and midpoint values are listed to illustrate the magnitude of the transition. The implementation of an annealing step
revealed a glass transition that was comparable to the experiment without annealing regarding extend and temperature range.
Crystallisation of gentamicin sulphate, therefore is not expected.
Figure 1
FDM. The collapse behaviour of gentamicin sulphate solution is exemplarily shown in Figure 1 for the 5% (w/v) sample. Figure 1(a) shows the typical appearance of the drying sample at a temperature where no collapse occurred yet. The dark and dense matrix
on the left represents the already dried amorphous matrix while the colourful area on the right shows the frozen structure.
With proceeding drying, the sublimation interface progresses, in this case, from left to right. The temperature of the onset
of collapse (Toc) is reached when the first structural changes can be visibly detected by formation of little pink holes or fissures in the
dried structure adjacent to the sublimation interface as a result of viscous flow (Figure 1(b)). During ongoing sublimation, the initial holes and gaps grow until the temperature of full collapse (Tfc) is reached, where the structural loss is so severe that there is no coherent dried-product matrix any more (Figure 1(c)). Table II summarises the results of the FDM measurements. As reported earlier, Tc is not a material constant but depends on concentration (3, 10, 11). In the case of gentamicin sulphate, an increase of approximately
3 °C can be observed in the range of 2–30% total solid content. The gap between Toc and Tfc (also denoted as the microcollapse regime) can offer valuable information about the temperature tolerance of the product
(5). Depending on the formulation, this temperature range can widen up to 10 or 15 °C (7, 8, 12), and recent publications
describe primary drying in the microcollapse region without significant macroscopic structural loss (5–7). With a difference
of about 2 °C, the gap between Toc and Tfc for the presented measurements is relatively small and does not increase distinctly with concentration.
Henning Gieseler, PhD, works in the Department of Pharmaceutics at the University of Erlangen, Erlangen, Germany 91058.
tel. +49 9131 85 29545, gieseler@freeze-drying.eu.
Articles by Henning Gieseler, PhD
