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Lyophilisation: difference between revisions

Diff·revision 31 → 32·12:03, 10 Feb 2025

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Revision 31 — 23:17, 31 Jan 2025
StopperingSteff (talk)
add citation
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Revision 32 — 12:03, 10 Feb 2025
ParentCatPansy (talk)
correct percentage: source reports placebo-adjusted
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89Vials do not all behave alike. Those at the edge of a shelf receive additional radiant heat from chamber walls and door, sublime faster, and reach higher product temperatures; this edge-vial effect can amount to several degrees and is the usual reason a cycle validated on a laboratory dryer fails at production scale.{{r|rambhatla2003}}89Vials do not all behave alike. Those at the edge of a shelf receive additional radiant heat from chamber walls and door, sublime faster, and reach higher product temperatures; this edge-vial effect can amount to several degrees and is the usual reason a cycle validated on a laboratory dryer fails at production scale.{{r|rambhatla2003}}
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+91{{note|Product temperature during primary drying is below shelf temperature, sometimes by 20 °C or more. Shelf temperature is not a proxy for product temperature, and a cycle described only by its shelf settings cannot be evaluated.}}
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91=== Collapse and eutectic melting ===93=== Collapse and eutectic melting ===
92Two distinct structural failures bound primary drying. In a system whose freeze-concentrate crystallises, exceeding the eutectic melting temperature produces liquid, and the vial dries as a shrunken residue or a glassy shell — usually described on inspection as melt-back. In an amorphous system, exceeding a temperature a few degrees above Tg′ allows viscous flow of the freeze-concentrated matrix into the pores that the sublimed ice has vacated. The dried layer loses its structure, and the result is a shrunken, sometimes glassy or foamed cake. The temperature at which this becomes observable by freeze-drying microscopy is the collapse temperature, Tc, conventionally 1–3 °C above Tg′ for small-molecule and peptide systems.{{r|tang2004}}94Two distinct structural failures bound primary drying. In a system whose freeze-concentrate crystallises, exceeding the eutectic melting temperature produces liquid, and the vial dries as a shrunken residue or a glassy shell — usually described on inspection as melt-back. In an amorphous system, exceeding a temperature a few degrees above Tg′ allows viscous flow of the freeze-concentrated matrix into the pores that the sublimed ice has vacated. The dried layer loses its structure, and the result is a shrunken, sometimes glassy or foamed cake. The temperature at which this becomes observable by freeze-drying microscopy is the collapse temperature, Tc, conventionally 1–3 °C above Tg′ for small-molecule and peptide systems.{{r|tang2004}}