Lyophilisation: difference between revisions
Diff·revision 13 → 14·17:15, 23 Jan 2025
Difference between revision 13 and revision 14 of Lyophilisation. 14 lines changed; the page grew by 1,442 bytes.
| Revision 13 — 23:19, 13 Jan 2025 OpenLabelOtto (talk) sentence case in headings per PP:MOS 15,434 bytes +1,940 | Revision 14 — 17:15, 23 Jan 2025 SurmountSurma (talk) correct the freezer temperature range given for long-term storage 16,876 bytes +1,442 | ||
|---|---|---|---|
| 101 | 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}} | 101 | 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}} |
| 102 | 102 | ||
| + | 103 | == Secondary drying == | |
| + | 104 | Once ice has gone, water remains sorbed to the solid — hydrogen-bonded to the peptide and to any amorphous excipient. Removing it requires desorption rather than sublimation, and desorption is driven by raising the product temperature well above the primary-drying value, typically to between 20 and 40 °C, while holding chamber pressure low.{{r|nail2002}} | |
| + | 105 | ||
| + | 106 | Desorption kinetics are fast at first and then slow markedly, so the last fraction of a percent of moisture is disproportionately expensive in time. Secondary drying is consequently the step most often truncated, and truncation is a common explanation for a cake that meets appearance specifications but exceeds its moisture specification.{{r|wang2000}} | |
| + | 107 | ||
| + | 108 | The heating ramp matters because the glass transition temperature of the partially dried solid rises as water leaves it. Early in secondary drying the solid is plasticised by residual water and its glass transition may be only slightly above the product temperature; heating too quickly can carry the product above the moving glass transition and cause the same collapse phenomenon seen in primary drying, at a much higher temperature. Conventional practice ramps shelf temperature at 0.1–0.5 °C per minute for this reason.{{r|tang2004}} | |
| + | 109 | ||
| 103 | == References == | 110 | == References == |
| 104 | {{reflist}} | 111 | {{reflist}} |
| ⋮ | ⋮ | ||
| 114 | <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> | 121 | <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> |
| 115 | <ref name="usp1207">United States Pharmacopeia, General Chapter <1207>, "Package Integrity Evaluation — Sterile Products". USP–NF, current revision.</ref> | 122 | <ref name="usp1207">United States Pharmacopeia, General Chapter <1207>, "Package Integrity Evaluation — Sterile Products". USP–NF, current revision.</ref> |
| + | 123 | ||
| + | 124 | == See also == | |
| + | 125 | * [[Reconstitution of lyophilised peptides]] | |
| + | 126 | * [[Karl Fischer titration]] | |
| + | 127 | * [[Vial]] | |
| + | 128 | * [[Vial filling and stoppering]] | |
| + | 129 | * [[Peptide aggregation]] | |
| 116 | 130 | ||
| 117 | {{DEFAULTSORT:Lyophilisation}} | 131 | {{DEFAULTSORT:Lyophilisation}} |