Freeze-dry microscopy: impact of nucleation temperature and excipient concentration on collapse temperature data

冻干显微镜:成核温度和赋形剂浓度对塌陷温度数据的影响

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Abstract

The objective of this study was to investigate the impact of nucleation temperature (T(n)) and excipient concentration on the collapse temperature data obtained from freeze-dry microscopy (FDM) experiments. T(n), the temperature of the onset of collapse (T(oc)), and the full collapse temperature (T(fc)) were determined for aqueous solutions of polyvinylpyrrolidone (PVP) 40 kDa and 2-(hydroxypropyl)-beta-cyclodextrin. Concentrations were varied from 1% to 20% (w/w) for PVP and from 1% to 30% (w/w) for the 2-(hydroxypropyl)-beta-cyclodextrin. Mutual correlation coefficients were calculated for the observed T(n), T(oc), and concentrations of the solutions. In addition, outliers were detected and eliminated by applying the leaving-one-out routine and calculating correlation coefficients without it. T(n) was found to be non-correlated with concentrations and only weakly correlated with T(oc). The correlation between these two temperatures was particularly poor for the solutions of the highest and lowest concentrations. In contrast, T(oc) correlated much better with the corresponding concentrations, resulting in a quadratic fit for PVP and a linear fit for 2-(hydroxypropyl)-beta-cyclodextrin.

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