Lyophilisation: difference between revisions
Diff·revision 15 → 16·16:40, 27 Oct 2024
Difference between revision 15 and revision 16 of Lyophilisation. 8 lines changed; the page grew by 812 bytes.
| Revision 15 — 07:30, 23 Oct 2024 CounterfeitCato (talk) merge two short sections 7,435 bytes ±0 | Revision 16 — 16:40, 27 Oct 2024 BacWaterBarnaby (talk) attribute range as a review estimate per talk 8,247 bytes +812 | ||
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| 5 | | Physical requirement = Pressure below the triple point of water | 5 | | Physical requirement = Pressure below the triple point of water |
| 6 | | Typical cycle length = 20–70 hours | 6 | | Typical cycle length = 20–70 hours |
| + | 7 | <!-- Representative process conditions --> | |
| + | 8 | | Freezing shelf temperature = −40 to −50 °C | |
| + | 9 | | Chamber pressure, primary drying = 5–20 Pa (roughly 40–150 mTorr) | |
| + | 10 | | Product temperature, primary drying = −40 to −20 °C | |
| + | 11 | | Shelf temperature, secondary drying = 20–40 °C | |
| 7 | }} | 12 | }} |
| 8 | 13 | ||
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| 13 | A lyophilisation cycle has three phases: freezing, primary drying in which ice is sublimed, and secondary drying in which water sorbed to the solid is desorbed. Each phase is bounded by a physical constraint. Freezing determines the ice-crystal structure and therefore the resistance the vapour must overcome later; primary drying must be conducted below the temperature at which the freeze-concentrated matrix loses rigidity; secondary drying must reach a residual moisture low enough for stability without over-drying a solid that may require a small amount of water for conformational integrity.{{r|tang2004,carpenter1997}} | 18 | A lyophilisation cycle has three phases: freezing, primary drying in which ice is sublimed, and secondary drying in which water sorbed to the solid is desorbed. Each phase is bounded by a physical constraint. Freezing determines the ice-crystal structure and therefore the resistance the vapour must overcome later; primary drying must be conducted below the temperature at which the freeze-concentrated matrix loses rigidity; secondary drying must reach a residual moisture low enough for stability without over-drying a solid that may require a small amount of water for conformational integrity.{{r|tang2004,carpenter1997}} |
| 14 | 19 | ||
| + | 20 | The finished cake is characterised by appearance, residual moisture, reconstitution time and the chemical purity of the reconstituted solution. None of these is visible from a purity figure alone, which is one reason a [[certificate of analysis]] that reports only [[Area percent purity|area percent purity]] leaves the physical quality of the vial undocumented.{{r|usp1207}} | |
| + | 21 | ||
| 15 | == Physical basis == | 22 | == Physical basis == |
| 16 | Water can pass directly from solid to vapour only at pressures below its triple point, which lies at 611.657 Pa and 0.01 °C. Above that pressure, warming ice produces liquid; below it, warming ice produces vapour. Every lyophilisation cycle therefore operates at a chamber pressure well beneath 611 Pa, typically between 5 and 20 Pa, so that heat supplied to the product drives sublimation rather than melting.{{r|nail2002}} | 23 | Water can pass directly from solid to vapour only at pressures below its triple point, which lies at 611.657 Pa and 0.01 °C. Above that pressure, warming ice produces liquid; below it, warming ice produces vapour. Every lyophilisation cycle therefore operates at a chamber pressure well beneath 611 Pa, typically between 5 and 20 Pa, so that heat supplied to the product drives sublimation rather than melting.{{r|nail2002}} |
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| 50 | <ref name="chang2009">Chang LL, Pikal MJ. "Mechanisms of protein stabilization in the solid state." ''Journal of Pharmaceutical Sciences'' 98(9):2886–2908 (2009).</ref> | 57 | <ref name="chang2009">Chang LL, Pikal MJ. "Mechanisms of protein stabilization in the solid state." ''Journal of Pharmaceutical Sciences'' 98(9):2886–2908 (2009).</ref> |
| 51 | <ref name="murphy2005">Murphy DM, Koop T. "Review of the vapour pressures of ice and supercooled water for atmospheric applications." ''Quarterly Journal of the Royal Meteorological Society'' 131(608):1539–1565 (2005).</ref> | 58 | <ref name="murphy2005">Murphy DM, Koop T. "Review of the vapour pressures of ice and supercooled water for atmospheric applications." ''Quarterly Journal of the Royal Meteorological Society'' 131(608):1539–1565 (2005).</ref> |
| + | 59 | <ref name="usp1207">United States Pharmacopeia, General Chapter <1207>, "Package Integrity Evaluation — Sterile Products". USP–NF, current revision.</ref> | |
| 52 | 60 | ||
| 53 | {{DEFAULTSORT:Lyophilisation}} | 61 | {{DEFAULTSORT:Lyophilisation}} |