Lyophilisation: difference between revisions
Diff·revision 27 → 28·11:45, 10 Jan 2025
Difference between revision 27 and revision 28 of Lyophilisation. 11 lines changed; the page grew by 1,601 bytes.
| Revision 27 — 17:20, 5 Jan 2025 UnitsUrsula (talk) rm unsourced claim per PP:V 13,494 bytes +317 | Revision 28 — 11:45, 10 Jan 2025 CouplingCillian (talk) expand §Cake attributes and their interpretation 15,095 bytes +1,601 | ||
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| 13 | | Product temperature, primary drying = −40 to −20 °C | 13 | | Product temperature, primary drying = −40 to −20 °C |
| 14 | | Shelf temperature, secondary drying = 20–40 °C | 14 | | Shelf temperature, secondary drying = 20–40 °C |
| + | 15 | <!-- Quality attributes --> | |
| + | 16 | | Residual moisture, usual target = below 3% w/w | |
| + | 17 | | Determined by = [[Karl Fischer titration]] or [[Loss on drying|loss on drying]] | |
| + | 18 | | Principal cake defect = Collapse above the collapse temperature | |
| + | 19 | | Reconstitution time, usual expectation = under 1 minute for a small peptide | |
| 15 | }} | 20 | }} |
| 16 | {{hatnote|For the reverse operation performed by the end user, see [[Reconstitution of lyophilised peptides]]. For measurement of the water that remains, see [[Karl Fischer titration]].}} | 21 | {{hatnote|For the reverse operation performed by the end user, see [[Reconstitution of lyophilised peptides]]. For measurement of the water that remains, see [[Karl Fischer titration]].}} |
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| 89 | Conservative practice therefore sets the target product temperature 2–5 °C below Tc and accepts the longer cycle. Aggressive cycles that run within a degree of Tc exist and are defensible when the critical temperature has been measured for the specific formulation rather than assumed from a table.{{r|tang2004}} | 94 | Conservative practice therefore sets the target product temperature 2–5 °C below Tc and accepts the longer cycle. Aggressive cycles that run within a degree of Tc exist and are defensible when the critical temperature has been measured for the specific formulation rather than assumed from a table.{{r|tang2004}} |
| 90 | 95 | ||
| + | 96 | === Endpoint determination === | |
| + | 97 | Primary drying ends when the last ice sublimes, and the transition is detectable because the vapour load on the condenser falls. Several signals are used. Comparative pressure measurement exploits the difference between a capacitance manometer, which reads total pressure, and a Pirani gauge, whose calibration depends on gas composition: as water vapour is replaced by nitrogen, the Pirani reading converges on the manometer reading, and the convergence marks the endpoint. Pressure-rise testing isolates the chamber briefly and measures the rate at which pressure recovers. Product thermocouples show a rise toward shelf temperature once no ice remains to consume heat, though a thermocouple perturbs nucleation in the vial it occupies and reads that vial rather than the batch.{{r|patel2010}} | |
| + | 98 | ||
| + | 99 | The practical difficulty is that the last vials to finish are not the ones being monitored. Endpoint criteria are therefore normally applied with a hold period appended, and the batch is held under primary-drying conditions for a defined time after the signal is observed.{{r|patel2010}} | |
| + | 100 | ||
| 91 | == References == | 101 | == References == |
| 92 | {{reflist}} | 102 | {{reflist}} |
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| 98 | <ref name="kasper2011">Kasper JC, Friess W. "The freezing step in lyophilization: physico-chemical fundamentals, freezing methods and consequences on process performance and quality attributes of biopharmaceuticals." ''European Journal of Pharmaceutics and Biopharmaceutics'' 78(2):248–263 (2011).</ref> | 108 | <ref name="kasper2011">Kasper JC, Friess W. "The freezing step in lyophilization: physico-chemical fundamentals, freezing methods and consequences on process performance and quality attributes of biopharmaceuticals." ''European Journal of Pharmaceutics and Biopharmaceutics'' 78(2):248–263 (2011).</ref> |
| 99 | <ref name="rambhatla2003">Rambhatla S, Pikal MJ. "Heat and mass transfer scale-up issues during freeze-drying, I: atypical radiation and the edge vial effect." ''AAPS PharmSci'' 5(2):article 14 (2003).</ref> | 109 | <ref name="rambhatla2003">Rambhatla S, Pikal MJ. "Heat and mass transfer scale-up issues during freeze-drying, I: atypical radiation and the edge vial effect." ''AAPS PharmSci'' 5(2):article 14 (2003).</ref> |
| + | 110 | <ref name="patel2010">Patel SM, Doen T, Pikal MJ. "Determination of end point of primary drying in freeze-drying process control." ''AAPS PharmSciTech'' 11(1):73–84 (2010).</ref> | |
| 100 | <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> | 111 | <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> |
| 101 | <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> | 112 | <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> |