# Evidence: drug-polymer complexation

Parent: — · class: molecular interaction · names merged here: drug-polymer complex; drug-polymer complexation; drug-polymer complexation in solution

5 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.

## 2010 Eerdenbrugh — Small Scale Screening To Determine the Ability of Different Polymers To Inhibit Drug Crystallization upon Rapid Solvent Evaporation · Solid state stability / Miscibility and drug-polymer interactions

[2010-van-eerdenbrugh-polymer-crystallization-inhibition-spin-coating-screen](../../../cards/2010-van-eerdenbrugh-polymer-crystallization-inhibition-spin-coating-screen/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · used · as: drug-polymer complexation

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | precipitation in drug-polymer solutions and nature of the precipitate — spin-coating solutions in EtOH (P1); bulk solution of LI-PAA (P6) — precipitation in BI-PAA, BI-PSSA, LI-PAA and LI-PSSA solutions at some weight ratios (ratios not printed); precipitation again in the LI-PAA bulk solution; microscopy: no crystalline material in the films made from these solutions | p.1330; p.1334 |
| C25 | claim, mechanism, authors: "it appears" | The precipitates formed by BI or LI with PAA and PSSA in solution are not crystalline; these drugs appear to complex with the polymers in solution, forming amorphous precipitates, as reported earlier for acidic polymer mixtures [rests on: R6; cited: ref 17] | p.1334 |

## 2011 Alonzo — Dissolution and Precipitation Behavior of Amorphous Solid Dispersions · Dissolution / B. Supersaturation from ASD dissolution

[2011-alonzo-asd-dissolution-precipitation-nanoparticles](../../../cards/2011-alonzo-asd-dissolution-precipitation-nanoparticles/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: drug-polymer complexation in solution

| id | kind | content | locator |
|---|---|---|---|
| R14 | record, measured and derived | receptor slope from linear regression over 10–40 min and its ratio with the crystalline slope (n = 3 except crystalline, n = 1; slope units not printed) — P4, 37 °C — sub-table below; text: equilibrium solubility of the crystalline phase about 1 µg/mL; ratio 4.8 for 5 µg/mL and 10 for 10 µg/mL; 8.5 pure amorphous, 9.5 for 50:50, 10.5 for 90:10 | Table 1, p.3325 |
| C23 | claim, conclusion, authors: asserted ("confirms") | The diffusion technique establishes that felodipine was not complexed with HPMC in bulk solution, unlike other systems under similar conditions [rests on: R14; cited: refs 26, 27] | p.3325 |

## 2015 Wegiel — Phase Behavior of Resveratrol Solid Dispersions Upon Addition to Aqueous media · Dissolution / B. Supersaturation from ASD dissolution

[2015-wegiel-resveratrol-solid-dispersions-aqueous-phase-behavior](../../../cards/2015-wegiel-resveratrol-solid-dispersions-aqueous-phase-behavior/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: drug-polymer complexation

| id | kind | content | locator |
|---|---|---|---|
| R5 | record, measured | initial series with increasing PVP concentration — crystalline resveratrol in PVP solutions in PB 6.8 — no clear trend in resveratrol solubility; gel-like precipitate formed as PVP concentration increased; no values printed | text, pdf p.5 |
| R6 | record, measured; derived (nominal and difference columns, relation named, not printed) | resveratrol dissolved after adding crystalline resveratrol to PVP solution — 18 ml of 20 mg/ml PVP in 50 mM PB pH 6.8, 37°C, 24 h (P3) — sub-table R6 | Table II and Fig. 3, pdf p.5 |
| R7 | record, measured | precipitate in PVP solutions — as R6 — ≈650 μg/ml added: complete dissolution, no precipitate; ≈1800 μg/ml added: small amount of gelatinous precipitate; higher additions: larger amount of gelatinous precipitate (photographs labelled precipitate size small to large, B to E); precipitate non-crystalline by PXRD; IR of isolated dried precipitate: contains resveratrol and PVP (data not shown) | text and Fig. 3, pdf p.5 |
| R19 | record, measured | resveratrol and polymer solution concentration vs dispersion loading — 15:85 resveratrol:HPMCAS in 32 ml PB 6.8, 24 h, 37°C (P10 donor) — sub-table R19 | Fig. 10a, pdf p.11; text, pdf p.7 |
| R20 | record, measured | membrane flux vs dispersion loading — side-by-side cell (P10), donor as R19 — sub-table R20 | Fig. 10b, pdf p.11; text, pdf p.7 |
| C29 | claim, mechanism, authors: discussion: It is proposed; suggesting; supporting; it appears; conclusions: asserted ("was observed") | The low concentrations from PVP dispersions are proposed to come from an insoluble resveratrol–PVP complex: the dispersion did not readily dissolve and crystalline resveratrol with PVP gave an amorphous precipitate, so dispersion insolubility appears to arise from complexation, hindering release. [rests on: R6, R7, R11, R12] | Discussion, pdf p.10; Conclusions, pdf p.13 |
| C33 | claim, mechanism, authors: it is clear; it can be inferred; caption: Evidence for | Resveratrol forms both soluble and insoluble complexes with PVP: the concentration increase in Fig. 3 and Table II is inferred to be soluble complex at certain ratios, and further resveratrol forms an insoluble complex that removes resveratrol from solution. [rests on: R6, R7] | Discussion, pdf p.10–11; Fig. 3 caption, pdf p.5 |
| C41 | claim, mechanism, authors: discussion: These results indicate; conclusions: asserted ("This situation was observed") | The results indicate that the resveratrol concentration enhancement from HPMCAS dispersions is mainly from a soluble resveratrol–HPMCAS complex; free resveratrol is at most about twice saturation, supersaturation is very limited and mass transport increases only modestly, unlike felodipine dispersions. [rests on: R19, R20, R24; cited: refs 29, 30] | Discussion, pdf p.12; Conclusions, pdf p.13 |

## 2023 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: Role of Drug Load and Molecular Interactions · Dissolution / A. Release mechanism and LoC

[2023-deac-asd-drug-load-molecular-interactions-loc](../../../cards/2023-deac-asd-drug-load-molecular-interactions-loc/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: drug-polymer complex

| id | kind | content | locator |
|---|---|---|---|
| C15 | claim, mechanism, authors: results: "likely due to"; discussion: "it is apparent" | The lower PHPH amorphous solubility with PVPVA is likely due to insoluble PHPH-PVPVA complexes, as reported for other compound-polymer pairs [rests on: R1; cited: refs 16, 39-42] | p.726, p.732 |
| C44 | claim, conclusion, authors: "was further demonstrated"; "Remarkable amounts" | Complex formation was further shown for PHPH and TIPP by the large PVPVA content of their amorphous insoluble phase, while MePHPH and MeTIPP insoluble phases held very little polymer [rests on: R3, R8] | p.732 |
| C47 | claim, conclusion, authors: asserted | MePHPH-PVPVA separates segregatively (insoluble phase rich in drug and poor in polymer, PVPVA in the aqueous phase) and PHPH-PVPVA associatively (insoluble phase enriched in both, a complex coacervate); in the conclusions TIPP is grouped with PHPH as associative and MeTIPP with MePHPH as segregative [rests on: R2, R3, R8; cited: refs 70, 71] | p.732-733, p.734 |

## 2024 Bapat — Interplay of Drug−Polymer Interactions and Release Performance for HPMCAS-Based Amorphous Solid Dispersions · Dissolution / A. Release mechanism and LoC

[2024-bapat-hpmcas-drug-polymer-complexation-release-performance](../../../cards/2024-bapat-hpmcas-drug-polymer-complexation-release-performance/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: drug-polymer complexation

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | control coprecipitation tests — pH 6.0, 50 mM phosphate, P9 — neat CNZ added to 460 µg/mL: solution turbid, pellet after centrifugation consisted of drug; neat HPMCAS added to 1 mg/mL: clear solution, no pellet; CNZ + HPMCAS co-added: precipitate pelleted by ultracentrifugation, containing HPMCAS (HPLC or colorimetry); precipitate amorphous by PLM | p.1469 |
| R11 | record, measured | percent HPMCAS complexed versus CNZ/COOH molar ratio (n = 3) — CNZ + HPMCAS-MF, pH 6.0, 50 mM phosphate, P9 — 0.25:1 ≈41; 0.5:1 ≈67; 0.75:1 ≈82; 1:1 ≈90; 1.5:1 ≈99; 2:1 ≈100; 3:1 ≈99 (read from Fig. 9); text: >90% at 1:1, ∼100% at 2:1, ∼40% at 0.25:1; plateau from approximately 1.5 mol drug per mol COOH (p.1475); 1:1 corresponds to ∼30% DL and 0.25:1 to 10% DL | Fig. 9, p.1473; text p.1470, p.1475 |
| R12 | record, measured | percent HPMCAS-MF complexed at given drug/COOH molar ratio, with the matching ASD DL, mean ± SD, n = 3 — pH 6.0, 50 mM phosphate, P9 — sub-table below | Table 4, p.1473 |
| R13 | record, measured | percent HPMCAS complexed with LOR versus pH (n = 3) — LOR/COOH 1:1, 50 mM phosphate (Table S1 rows a-e, g, h), P9 — pH 5.8 ≈85; 6.0 ≈70; 6.2 ≈60; 6.3 ≈50; 6.5 ≈25; 6.8 ≈5; 7.5 ≈2 (read from Fig. 10); complexation rises as pH falls from 7.5 to 5.8 | Fig. 10, p.1473; text p.1472 |
| R16 | record, measured | percent HPMCAS complexed with LOR at three ionic strengths (n = 3) — LOR:HPMCAS 1:1, pH 6, P9 — 100 mM phosphate (μ = 130 mM) ≈48; 50 mM phosphate + NaCl (μ = 150 mM) ≈65; 50 mM phosphate (μ = 63 mM) ≈70 (read from Fig. S1) | Fig. S1, SI p.3 |
| C19 | claim, conclusion, authors: asserted ("Interestingly") | At 1:1 only ca. 5-17% of the polymer complexed with unionized RTV, CIL, INDester and anionic IND, whereas ionized or partially ionized cationic LOR, CNZ and CLO gave ≥70%; unionized PHPH also complexed extensively [rests on: R12] | p.1471-1472 |
| C29 | claim, conclusion, authors: asserted | HPMCAS dissolves to ≈5 mg/mL at pH 6.0 from extensive ionization, but with certain lipophilic drugs its solubility at this pH was reduced by drug-polymer complexation, leading to precipitation [rests on: R10, R12; M9] | p.1474 |