# Evidence: polymer rejection at the crystal growth front

Parent: — · class: kinetics · names merged here: drug-polymer demixing at the growth front; polymer accumulation at the crystal growth front; polymer enrichment at the crystal growth front; polymer rejection at the crystal growth front

3 papers measured or used it, 1 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.

## 2006 Konno — Influence of Different Polymers on the Crystallization Tendency of Molecularly Dispersed Amorphous Felodipine · Solid state stability / Physical stability

[2006-konno-felodipine-polymer-crystallization-nucleation-solid-dispersions](../../../cards/2006-konno-felodipine-polymer-crystallization-nucleation-solid-dispersions/paper.html) · Solid state stability / Physical stability · used · as: polymer accumulation at the crystal growth front

| id | kind | content | locator |
|---|---|---|---|
| C39 | claim, mechanism, authors: "potentially relevant"; "it is unlikely"; "would impede"; "may also increase" | A crystallizing drug rejects the miscible polymer, which accumulates at the crystal-amorphous interface if it diffuses away slowly, as expected below Tg; this polymer-rich layer would impede drug transport (lower local drug concentration, higher local Tg) and may raise the energy penalty for new surface (ΔGs); a similar mechanism was proposed for indomethacin with low PVP [rests on: argument only; cited: refs 45, 46] | p.2703 |
| C42 | claim, conclusion, authors: "Some evidence"; "It is thought"; "requires further investigation" | Fig. 2 gives some evidence for the accumulation mechanism: polymers disrupt uniform spherulitic growth, and small droplets in ring-like patterns and at crystal edges are thought to be a polymer-rich phase; this needs further investigation [rests on: R2] | p.2703 |

## 2010 Kestur — Role of polymer chemistry in influencing crystal growth rates from amorphous felodipine · Solid state stability / Miscibility and drug-polymer interactions

[2010-kestur-polymer-chemistry-felodipine-crystal-growth-inhibition](../../../cards/2010-kestur-polymer-chemistry-felodipine-crystal-growth-inhibition/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · used · as: drug-polymer demixing at the growth front

| id | kind | content | locator |
|---|---|---|---|
| C42 | claim, mechanism, authors: "can be rationalized"; "This speculation" | Crystal growth requires drug–polymer demixing so that drug molecules can join the crystal at the growth front; if mixing is favourable, demixing is an activated process that breaks drug–polymer interactions, and stronger interactions make demixing less favourable and slow the addition of molecules to the growth front [rests on: argument only] | p.2396-2397 |
| C43 | claim, mechanism, authors: "would be expected"; "This speculation is supported" | The temperature data support the demixing picture: at high temperature thermal energy weakens and disrupts drug–polymer hydrogen bonds, especially weak ones, so demixing is easier and the polymers inhibit poorly; at lower temperature hydrogen bonding matters more, the polymers inhibit better and differ more [rests on: R5, R6] | p.2397 |

## 2010 Kestur — Effects of the Molecular Weight and Concentration of Polymer Additives, and Temperature on the Melt Crystallization Kinetics of a Small Drug Molecule · Solid state stability / Physical stability

[2010-kestur-pvp-mw-concentration-temperature-felodipine-melt-crystallization](../../../cards/2010-kestur-pvp-mw-concentration-temperature-felodipine-melt-crystallization/paper.html) · Solid state stability / Physical stability · used · as: polymer rejection at the crystal growth front

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: asserted; "possible accumulation" | Certain polymers inhibit crystallization of amorphous drugs even below 10 wt%; the mechanism at such low concentrations is unexplained; proposed explanations are polymer accumulation at the interface between crystal and amorphous matrix (ref 14), local antiplasticization (ref 15), decreased molecular mobility (ref 17) and specific drug-polymer interactions such as hydrogen bonding (ref 18) [rests on: cited: refs 8-18] | p.3585-3586 |
| C39 | claim, prior hypothesis, authors: "it is not unreasonable to expect"; "may appear surprising" | Polymer would be expected to accumulate at the crystal surface as crystallization proceeds, since polymer diffusivity should be much smaller than the crystallization speed, and in mixtures of crystalline and noncrystalline polymers crystallization expels much of the amorphous polymer [rests on: cited: ref 42] | p.3593 |
| C41 | claim, conclusion, authors: "we expect"; "confirming" | With complete expulsion a large accumulation of PVP is expected near the crystallization front and grows over time; even when 99% of the polymer is incorporated (ε = 0.01) the surface concentration stays considerably time-dependent; raising Dt by 2 orders of magnitude does not change this, so using Dt for Dm is acceptable for a qualitative picture [rests on: R20, R21, R22] | p.3594 |
| R20 | record, simulated | predicted PVP concentration profiles c(r,t) (weight fraction; values ≈, read from Fig. 11) — P10: 3 wt% PVP K-29/32 (c∞ = 0.03), 100 °C, Dt = 4.976 × 10⁻¹⁶, v = 2.37 × 10⁻⁸ m/s, ε = 1; t = 5, 10, 20, 50, 100, 150, 200 s — a sharp peak at the crystal front at r ≈0.12, ≈0.24, ≈0.47, ≈1.19, ≈2.37, ≈3.56, ≈4.74 µm with peak weight fractions ≈0.08, ≈0.13, ≈0.22, ≈0.48, ≈0.90, ≈1.33, ≈1.75; profiles fall back to 0.03 within ≈0.2-0.3 µm ahead of the front | Fig. 11, p.3594 |
| R21 | record, simulated | predicted PVP concentration at the crystal surface c(R(t),t) versus time (weight fraction; values ≈, read from Fig. 12) — as R20, ε = 1, 0.1, 0.01, 0-500 s — all start at 0.03; ε = 1 reaches 0.50 at ≈52 s; ε = 0.1 rises to ≈0.46 at 500 s; ε = 0.01 rises to ≈0.07 at 500 s; text: at ε = 0.01 the surface concentration remains considerably time-dependent | Fig. 12, p.3594 |

## Mentioned only

- 2013 Kestur — [2013-kestur-particle-size-crystallization-amorphous-felodipine-pvp](../../../cards/2013-kestur-particle-size-crystallization-amorphous-felodipine-pvp/paper.html) · Solid state stability / Physical stability (ref C31 R27)