# Evidence: solution-mediated phase transformation

Parent: — · class: kinetics · names merged here: solution-mediated phase transformation; solution-mediated polymorphic transformation; solvent-mediated phase transformation

4 papers measured or used it, 3 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.

## 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 · measured · as: solution-mediated phase transformation

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured | indomethacin concentration–time on dissolution of amorphous solid, no polymer (µg/mL) — P3; pH 2 buffer; 300 µg solid per mL — sub-table below. Text: peak around 15 µg/mL at 25 °C and 11.5 µg/mL at 37 °C; at both temperatures the concentration drops after the maximum | Fig. 7, p.612-613 |
| R17 | record, measured | indomethacin concentration–time after solvent shift, 37 °C (µg/mL) — P4; pH 2 buffer — sub-table below. Text: without polymer the concentration drops rapidly; with HPMC the initial concentration is held for about 2.5 h, then decreases; with PVP an initial drop to about 33 µg/mL, fairly steady until 160 min, then decreasing | Fig. 13, p.615 |
| R18 | record, measured | indomethacin concentration–time after solvent shift, 25 °C (µg/mL) — P4; pH 2 buffer — sub-table below. Text: initial concentration around 25 µg/mL; without polymer a 25 min delay before desupersaturation; with either polymer a very slow desupersaturation over the 4 h experiment to approximately 20 µg/mL | Fig. 14, p.615 |
| R19 | record, measured | polarized-light micrographs of amorphous indomethacin in pH 2 buffer — P9; room temperature — no polymer: (A) initially, amorphous particles and no crystals; (B) after 60 min, dendritic needle-like crystals in several areas of the liquid between the particles (one circled); no crystallization of the amorphous solid seen. With PVP or HPMC at 250 µg/mL (images not shown): no needle-like crystals formed, text "completely arrested" | Fig. 15, p.615 |
| C16 | claim, conclusion, authors: "suggesting" | The fall in concentration after the maximum at both temperatures reflects indomethacin crystallizing from the supersaturated solution [rests on: R7] | p.612 |
| C31 | claim, conclusion, authors: "indicating"; polymers: "quite clear" | The dendritic needle-like crystals in the micrographs show indomethacin crystallizing from the solution phase, with no evidence of crystallization of the amorphous solid; with PVP and HPMC this solution-mediated crystal formation was completely arrested [rests on: R19] | p.615 |
| C44 | claim, conclusion, authors: asserted | Solution-mediated transformation was the dominant mechanism depleting the elevated concentrations of indomethacin at 25 °C and of felodipine with pre-dissolved polymers [rests on: R18, R19, R4, R6] | p.617 |

## 2014 Raina — Impact of Polymers on the Crystallization and Phase Transition Kinetics of Amorphous Nifedipine during Dissolution in Aqueous Media · Dissolution / B. Supersaturation from ASD dissolution

[2014-raina-polymers-nifedipine-crystallization-phase-transition-dissolution](../../../cards/2014-raina-polymers-nifedipine-crystallization-phase-transition-dissolution/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: solution-mediated phase transformation

| id | kind | content | locator |
|---|---|---|---|
| C34 | claim, prior hypothesis, authors: asserted | A solution-mediated phase transformation has three stages: dissolution of the metastable phase to a supersaturated solution, nucleation of the new phase driven by supersaturation, and its growth, which depletes the solution so that more metastable phase dissolves [rests on: argument only] | p.3574 |
| C35 | claim, mechanism, authors: "as they appear to be" | When nucleation and growth are rapid, as they appear to be for nifedipine, dissolution controls the solution-mediated transformation [rests on: R12, R13] | p.3574 |
| C36 | claim, mechanism, authors: "may"; "would"; "may explain" | The dispersion can dissolve faster and may reach higher supersaturation before crystallizing; higher supersaturation would give faster nucleation and many small crystals, whose larger surface area speeds their dissolution and offers more surface for heterogeneous nucleation, which may explain the faster γ-to-α conversion of the ASDs [rests on: R13, R14] | p.3574 |

## 2016 Lu — Vemurafenib: A Tetramorphic System Displaying Concomitant Crystallization from the Supercooled Liquid · Solid state stability / Crystallization tendency

[2016-lu-vemurafenib-tetramorphic-cold-crystallization-supercooled-liquid](../../../cards/2016-lu-vemurafenib-tetramorphic-cold-crystallization-supercooled-liquid/paper.html) · Solid state stability / Crystallization tendency · measured · as: solvent-mediated phase transformation

| id | kind | content | locator |
|---|---|---|---|
| R23 | record, measured | solvent-mediated β-to-α conversion — room temperature (P8) — β converted to α; data not shown | p.20 |
| C38 | claim, conclusion, authors: "appears"; "at least at the higher temperatures studied"; "confirming" | α appears to be the most stable polymorph at least at the higher temperatures studied, since all other forms eventually transform to it; solvent-mediated conversion of β to α shows α is also the room-temperature stable form [rests on: R13, R15, R17, R23] | p.19-20 |

## 2017 Correasoto — Second harmonic generation microscopy as a tool for the early detection of crystallization in spray dried dispersions · Characterization methods / Solid-state methods

[2017-correa-soto-shg-early-crystallization-spray-dried-asds](../../../cards/2017-correa-soto-shg-early-crystallization-spray-dried-asds/paper.html) · Characterization methods / Solid-state methods · used · as: solvent-mediated phase transformation

| id | kind | content | locator |
|---|---|---|---|
| C39 | claim, mechanism, authors: "quite unexpected"; "Clearly"; "further studies are needed" | Hollow organic crystals are rare and in all reported cases arise from solvent-mediated phase transformation (the new phase grows on the surface of the old one, leaving a hollow centre); such a transformation is not responsible for the hollow FTM crystals, and further studies are needed [rests on: argument only; R16] | p.94 |

## Mentioned only

- 2008 Marsac — [2008-marsac-peo-water-spontaneous-drug-crystallinity-loss](../../../cards/2008-marsac-peo-water-spontaneous-drug-crystallinity-loss/paper.html) · Solid state stability / PEG dispersions (ref 32)
- 2015 Chen — [2015-chen-bile-salts-crystallization-inhibitors-supersaturated-solutions](../../../cards/2015-chen-bile-salts-crystallization-inhibitors-supersaturated-solutions/paper.html) · Dissolution / D. Crystallization from solution (ref 17)
- 2015 Chen — [2015-chen-surfactants-crystallization-celecoxib-hpmcas-asd-suspensions](../../../cards/2015-chen-surfactants-crystallization-celecoxib-hpmcas-asd-suspensions/paper.html) · Dissolution / B. Supersaturation from ASD dissolution (ref C1)