Lyophilisation: difference between revisions
Diff·revision 12 → 13·02:53, 12 Oct 2024
Difference between revision 12 and revision 13 of Lyophilisation. 9 lines changed; the page grew by 2,023 bytes.
| Revision 12 — 10:46, 8 Oct 2024 FreightFenna (talk) attribute claim in-text 4,669 bytes +38 | Revision 13 — 02:53, 12 Oct 2024 DrTitration (talk) rv restoration of unsourced claim 6,692 bytes +2,023 | ||
|---|---|---|---|
| 30 | Values follow the standard formulations reviewed by Murphy and Koop.{{r|murphy2005}} The table explains a practical asymmetry of the process: a cycle run with the product at −40 °C rather than −30 °C loses roughly two-thirds of its driving force, and a cycle run 5 °C warmer than intended may dry substantially faster while risking the structural failure described below. | 30 | Values follow the standard formulations reviewed by Murphy and Koop.{{r|murphy2005}} The table explains a practical asymmetry of the process: a cycle run with the product at −40 °C rather than −30 °C loses roughly two-thirds of its driving force, and a cycle run 5 °C warmer than intended may dry substantially faster while risking the structural failure described below. |
| 31 | 31 | ||
| + | 32 | == Freezing == | |
| + | 33 | Cooling an aqueous solution below 0 °C does not immediately produce ice. Nucleation requires supercooling, and in clean pharmaceutical solutions supercooling of 10–20 °C below the equilibrium freezing point is routine. The temperature at which nucleation happens to occur determines the number and size of the ice crystals formed: nucleation close to 0 °C produces few, large crystals and a coarse, low-resistance dried structure, whereas deep supercooling produces many small crystals and a fine structure that impedes vapour escape.{{r|searles2001,kasper2011}} | |
| + | 34 | ||
| + | 35 | Because nucleation is stochastic, vials within one batch nucleate at different temperatures and therefore dry at different rates. This is a principal source of vial-to-vial variability in residual moisture and cake appearance, and it is the reason controlled-nucleation techniques — depressurisation, ice fog, or brief pressure cycling — have been developed to force all vials to nucleate within a narrow window.{{r|kasper2011}} | |
| + | 36 | ||
| + | 37 | As ice forms, solutes are excluded from the crystal lattice and concentrate in the remaining liquid. This freeze concentration continues until the residual phase either crystallises at a eutectic temperature or becomes so viscous that it vitrifies. The temperature at which the maximally freeze-concentrated amorphous phase undergoes its glass transition is written Tg′ and is a formulation property, not a process setting. | |
| + | 38 | ||
| 32 | == References == | 39 | == References == |
| 33 | {{reflist}} | 40 | {{reflist}} |
| ⋮ | ⋮ | ||
| 36 | <ref name="tang2004">Tang X, Pikal MJ. "Design of freeze-drying processes for pharmaceuticals: practical advice." ''Pharmaceutical Research'' 21(2):191–200 (2004).</ref> | 43 | <ref name="tang2004">Tang X, Pikal MJ. "Design of freeze-drying processes for pharmaceuticals: practical advice." ''Pharmaceutical Research'' 21(2):191–200 (2004).</ref> |
| 37 | <ref name="carpenter1997">Carpenter JF, Pikal MJ, Chang BS, Randolph TW. "Rational design of stable lyophilized protein formulations: some practical advice." ''Pharmaceutical Research'' 14(8):969–975 (1997).</ref> | 44 | <ref name="carpenter1997">Carpenter JF, Pikal MJ, Chang BS, Randolph TW. "Rational design of stable lyophilized protein formulations: some practical advice." ''Pharmaceutical Research'' 14(8):969–975 (1997).</ref> |
| + | 45 | <ref name="searles2001">Searles JA, Carpenter JF, Randolph TW. "The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature-controlled shelf." ''Journal of Pharmaceutical Sciences'' 90(7):860–871 (2001).</ref> | |
| + | 46 | <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> | |
| 38 | <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> | 47 | <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> |
| 39 | <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> | 48 | <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> |