# Evidence: metastable zone

Parent: — · class: kinetics · names merged here: metastable zone

3 papers measured or used it, 0 only mentioned it (of 207 kept papers). Papers in year order; each section heading ends with the paper's category / subcategory. Generated by tools/build_evidence.py from registry/concepts.csv and the cards; do not edit.

## 2008 Konno — Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine · Dissolution / B. Supersaturation from ASD dissolution

[2008-konno-polymer-type-felodipine-asd-dissolution](../../../cards/2008-konno-polymer-type-felodipine-asd-dissolution/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: metastable zone

| id | kind | content | locator |
|---|---|---|---|
| C27 | claim, mechanism, authors: "it appears"; "presumably" | After the initial drop the solution has moved from the labile into the metastable zone, where nucleation is no longer spontaneous and only crystal growth can lower the concentration; if growth is inhibited the concentration stays elevated [rests on: argument only] | p.498 |

## 2010 Alonzo — Understanding the Behavior of Amorphous Pharmaceutical Systems during Dissolution · Dissolution / B. Supersaturation from ASD dissolution

[2010-alonzo-amorphous-pharmaceutical-dissolution-crystallization-polymers](../../../cards/2010-alonzo-amorphous-pharmaceutical-dissolution-crystallization-polymers/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: metastable zone

| id | kind | content | locator |
|---|---|---|---|
| C43 | claim, generalisation, authors: asserted | Framework of Fig. 16: dissolution rate scales with surface area and a concentration difference, nucleation rate with supersaturation, growth rate with a concentration difference; matrix crystallization fast relative to dissolution gives no supersaturation, while slow or absent matrix crystallization leaves crystallization from the supersaturated solution as the cause of lost performance; above the metastable zone nucleation and growth deplete the solution, and the higher the supersaturation the higher these rates [rests on: E3, E4, E5; cited: refs 35–37] | p.615-617 |

## 2013 Ilevbare — Liquid-Liquid Phase Separation in Highly Supersaturated Aqueous Solutions of Poorly-Water Soluble Drugs – Implications for Solubility Enhancing Formulations · Dissolution / C. Amorphous solubility and LLPS

[2013-ilevbare-llps-supersaturated-poorly-water-soluble-drugs](../../../cards/2013-ilevbare-llps-supersaturated-poorly-water-soluble-drugs/paper.html) · Dissolution / C. Amorphous solubility and LLPS · measured · as: metastable zone

| id | kind | content | locator |
|---|---|---|---|
| R11 | record, measured | temperature-concentration phase diagram of ritonavir: binodal (TL-L), spinodal (Tsp), CL-L and equilibrium crystalline solubility — Fig. 7 "Phase diagram of ritonavir"; binodal and spinodal by P12, CL-L by P5, solubility by P1; horizontal error bars on binodal and spinodal points — binodal TL-L ≈11.4 °C at ≈58 µg/mL, ≈15.7 °C at ≈50, ≈20.0 °C at ≈46.5 and ≈24.7 °C at ≈42.7 µg/mL; spinodal Tsp at the same concentrations ≈17.6, ≈23.4, ≈25.2 and ≈29.2 °C; CL-L ≈57.9 at 10, ≈49.9 at 15, ≈46.4 at 20, ≈42.6 at 25, ≈37.1 at 35, ≈39.7 at 45, ≈42.5 at 55, ≈49.6 at 60 and ≈54.8 µg/mL at 65 °C; equilibrium solubility ≈1.2 at 25, ≈2.5 at 37 and ≈6.4 µg/mL at 50 °C; labels: (I) on an arrow at 35 °C between solubility and CL-L, (IIa) between binodal and spinodal points, (IIb) beyond the spinodal points (all read from Fig. 7) | Fig. 7, p.31; text p.17 |
| C32 | claim, generalisation, authors: asserted | In region I the solution is supersaturated with respect to the crystal, so nucleation and growth can occur; above the binodal (IIa) it is supersaturated with respect to both LLPS and crystal nucleation, and LLPS occurs only if crystal nucleation is slow relative to LLPS; above the spinodal (IIb) demixing is spontaneous by spinodal decomposition; between binodal and spinodal LLPS is activated and requires nucleation of the new liquid phase [rests on: R11; cited: ref 12] | p.17 |
| C34 | claim, conclusion, authors: asserted ("It is clear") | The metastable zone for LLPS (distance between binodal and spinodal) is small, as observed previously, consistent with the agreement between continuous addition and cloud and clear points [rests on: R11; cited: ref 12] | p.17-18 |