کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2083992 | 1545340 | 2014 | 8 صفحه PDF | دانلود رایگان |
• TVIS measures the composite impedance at the glass wall-solution interface.
• Solute crystallization is manifested with secondary changes in fpeak and R.
• Inclusion of non-crystallizing solute will inhibit the crystallization on mannitol.
The aim of this work was to evaluate the application of through-vial impedance spectroscopy in the measurement of eutectic crystallization during the freezing stage of the lyophilisation cycle.Impedance measurements of various sugar solutions (mannitol 5%, 10% and 15% w/v, sucrose 5% w/v and mannitol 5% w/v, and sucrose 5% w/v solutions) were taken during a freeze–thaw cycle, over a frequency range 10–106 Hz with a scan interval of 1.5 min, using measurement vials with externally attached electrodes connected to a high resolution impedance analyzer.Estimates for the electrical resistance of the mannitol solutions record the exothermic crystallization of mannitol at a temperature of −24 °C during the temperature ramp down stage of the freezing cycle, which is in close agreement with the off-line DSC measurement of −22 °C. The freezing profile of a 5% mannitol solution with 5% sucrose (a component that does not crystallize in the frozen solution) demonstrated the inhibition of mannitol crystallization (with the implication that the product will then require sub-Tg′ freezing and drying).The work suggests a role for through-vial impedance spectroscopy in the concurrent development of the product formulation and freeze drying cycle without the uncertainty introduced when using off-line date to define the critical process parameters.
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Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 87, Issue 3, August 2014, Pages 598–605