# Evidence: acid-base interaction

Parent: — · class: molecular interaction · names merged here: acid-base interaction

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.

## 2011 Eerdenbrugh — An ab initio polymer selection methodology to prevent crystallization in amorphous solid dispersions by application of crystal engineering principles · Solid state stability / Miscibility and drug-polymer interactions

[2011-van-eerdenbrugh-ab-initio-polymer-selection-asd-crystallization](../../../cards/2011-van-eerdenbrugh-ab-initio-polymer-selection-asd-crystallization/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: acid-base interaction

| id | kind | content | locator |
|---|---|---|---|
| R8 | record, measured | ATR-FTIR of anthranilic acid with PAA and PSSA (data not shown) — melts at equimolar functional groups (P4) — spectral signs of an acid–base reaction with PSSA and not with PAA (spectra not shown) | p.6175 |
| R15 | record, cited (CSD LIDCAN10/LIDCAN11); measured (ATR-FTIR, data not shown) | lidocaine intramolecular contact and proton transfer — lidocaine crystal structures; lidocaine with PSSA and PAA (P4) — intramolecular hydrogen bond reported in the crystals with N–H···N angles 99.0-112.4°; ATR-FTIR: proton transfer with PSSA, not with PAA (spectra not shown) | p.6176 |
| R17 | record, cited (ref 34); measured (ATR-FTIR, data not shown) | dibucaine hydrogen bonding and proton transfer — dibucaine crystal; dibucaine with PSSA and PAA (P4) — amide groups form N–H···O hydrogen bonds in the crystal; ATR-FTIR: proton transfer with PSSA, not with PAA (spectra not shown) | p.6176 |
| C22 | claim, mechanism, authors: "suggest"; "might occur"; "indeed pointed to" | The good anthranilic acid–PSSA performance, a deviation from the pattern, may come from an acid–base reaction (PSSA pKa −1.5 acidic, anthranilic acid 2.0 basic), similar to zwitterion formation in its crystals; ATR-FTIR pointed to an acid–base reaction with PSSA and not with PAA [rests on: R3.e, R8, R7, R1.g, R2.g] | p.6175 |
| C23 | claim, mechanism, authors: "apparently" | The much higher acidic pKa of PAA (4.5) and the much lower basic pKa of flufenamic acid (−2.1) apparently prevent this type of reaction [rests on: R2.c, R9, R8] | p.6175 |

## 2013 Wegiel — Crystallization of Amorphous Solid Dispersions of Resveratrol during Preparation and Storage—Impact of Different Polymers · Solid state stability / Physical stability

[2013-wegiel-resveratrol-asd-polymer-crystallization-stability](../../../cards/2013-wegiel-resveratrol-asd-polymer-crystallization-stability/paper.html) · Solid state stability / Physical stability · measured · as: acid-base interaction

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured | E100 bands at 2820 and 2770 cm−1 (reported in ref 32 as non-ionized dimethylamino groups) — P5, E100 films 0-60% resveratrol — present in neat E100; intensity decreased quickly as resveratrol increased; absent at 50% resveratrol (text) | Fig. 4 (OH-region panel), p.177; text p.175 |
| C15 | claim, conclusion, authors: "provided evidence"; abstract: "Somewhat surprisingly", "showed evidence" | The loss of the 2820 and 2770 cm−1 bands of non-ionized dimethylamino groups is evidence of an acid-base reaction between resveratrol and E100, so resveratrol interacts with E100 through ionic interactions and weak hydrogen bonds to the E100 carbonyl [rests on: R7, R6; cited: ref 32] | p.171, p.175 |
| C38 | claim, mechanism, authors: "likely" | E100 dispersions resisted moisture-induced crystallization, likely due to the strong polymer-resveratrol acid-base interactions [rests on: R12.g, R7] | p.183 |

## 2014 Wegiel — Curcumin amorphous solid dispersions: the influence of intra and intermolecular bonding on physical stability · Solid state stability / Physical stability

[2014-wegiel-curcumin-asd-intramolecular-bonding-physical-stability](../../../cards/2014-wegiel-curcumin-asd-intramolecular-bonding-physical-stability/paper.html) · Solid state stability / Physical stability · measured · as: acid-base interaction

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured | E100 bands at 2820 and 2770 cm-1 (assigned to non-ionized dimethylamino groups, cited ref 32) versus curcumin content — E100 films, 20, 40, 60, 80 wt% curcumin (P1, P4) — text: both bands decrease quickly in intensity as curcumin rises and are fully eradicated at 60% curcumin; figure: both bands clear in neat E100 and at 20%, weak at 40%, at most a faint shoulder near ≈2770 at 60%, absent at 80% (read from Fig. 8, upper panel) | Fig. 8, p.981 |
| R10 | record, measured | colour of powders — curcumin and 75:25 curcumin-polymer dispersions (P10) — E100 dispersion rich dark red; curcumin and the PVP, CMCAB, HPMCAS and HPMC dispersions orange | Fig. 9, p.981 |
| C16 | claim, conclusion, authors: results: "provides evidence"; discussion: "it is apparent" | The loss of the 2820 and 2770 cm-1 bands shows ionized dimethylamino groups and an acid-base (ionic) interaction between curcumin's acidic phenol hydroxyls and E100's amino groups [rests on: R7; M1 and M5 pKa] | p.981, p.984 |
| C20 | claim, mechanism, authors: "can be attributed to"; "in good agreement" | The colour change with E100 arises from a change in curcumin's ionization state caused by the basic polymer, in agreement with the IR inference [rests on: R7, R10, R25] | p.981-982 |
| C37 | claim, mechanism, authors: discussion: "appear to be the reason"; conclusions: asserted | Ionic drug-polymer interactions are the reason for the extremely good stability of curcumin-E100 dispersions, since little curcumin-E100 hydrogen bonding was found; ionic interactions with E100 were not hindered and, when formed, increased physical stability [rests on: R7, R13.b, R23] | p.984, p.985 |

## 2017 Saboo — Water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) amorphous solid dispersions: Insights with confocal fluorescence microscopy · Solid state stability / Physical stability

[2017-saboo-water-induced-miconazole-pvpva-asd-phase-separation](../../../cards/2017-saboo-water-induced-miconazole-pvpva-asd-phase-separation/paper.html) · Solid state stability / Physical stability · used · as: acid-base interaction

| id | kind | content | locator |
|---|---|---|---|
| C36 | claim, mechanism, authors: "may arise" | Fluorescein's preference for the drug-rich phase may arise from specific interactions between weakly basic miconazole and acidic fluorescein [rests on: R11] | pdf p.18 |

## 2022 Hiew — Balancing Solid-State Stability and Dissolution Performance of Lumefantrine Amorphous Solid Dispersions: The Role of Polymer Choice and Drug−Polymer Interactions · Solid state stability / Miscibility and drug-polymer interactions

[2022-hiew-lumefantrine-asd-stability-dissolution-polymer-choice](../../../cards/2022-hiew-lumefantrine-asd-stability-dissolution-polymer-choice/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: acid-base interaction

| id | kind | content | locator |
|---|---|---|---|
| R19 | record, measured | subtraction FTIR (25% DL ASD minus amorphous lumefantrine) versus neat polymer — P13; 25% DL HPMCAS, HPMCP, CAP, Eudragit L 100 ASDs — additional peaks between 1594−1560 cm−1 and 1410−1343 cm−1; positions marked in Fig. 7: HPMCAS 1594, 1574, 1343; HPMCP 1574, 1343; CAP 1560, 1410; Eudragit L 100 1594, 1574, 1343 cm−1 | p.405; Fig. 7, p.404 |
| R20 | record, measured | percentage protonation of lumefantrine from N 1s XPS (mean with SD, n = 3) — P16; 25% DL compacts — sub-table below; N 1s spectra in Fig. 8 | Table 4, p.405; Fig. 8, p.405 |
| C25 | claim, conclusion, authors: "provides evidence" | The extra carboxylate stretching bands in the subtracted spectra provide evidence of an acid−base interaction between lumefantrine and the enteric polymers [rests on: R19] | p.405 |
| C48 | claim, conclusion, authors: "indicated"; "Thus" | XPS indicated some salt formation between enteric polymer and drug in the solvent-evaporated ASDs, in agreement with earlier studies, so ionic drug−polymer interactions existed before hydration [rests on: R20; cited: refs 37, 46] | p.408 |