# Evidence: incomplete drug release

Parent: — · class: transport and absorption · names merged here: incomplete drug release

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.

## 2018 Dening — Supersaturation Potential of Ordered Mesoporous Silica Delivery Systems. Part 1: Dissolution Performance and Drug Membrane Transport Rates · Mesoporous silica / Mesoporous silica

[2018-dening-ordered-mesoporous-silica-supersaturation-dissolution-flux](../../../cards/2018-dening-ordered-mesoporous-silica-supersaturation-dissolution-flux/paper.html) · Mesoporous silica / Mesoporous silica · measured · as: incomplete drug release

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | ritonavir concentration vs time, 25% w/w formulation — P6; buffer pH 6.8, 37 °C; dose at 100% (S 7.8, maximum 28 µg/mL) and 50% (S 3.9, maximum 14 µg/mL) of amorphous solubility; n = 3, mean ± SD — sub-table below; text: supersaturated within 5 min at both doses; S 7.8: no further release over 2 h, maximum 14 µg/mL, ≈50% release; S 3.9: ≈10 µg/mL maintained over 2 h, release 70% | Fig. 2, p.3492; text p.3492-3493 |
| R18 | record, measured | concentration and percent released during sequential dilution — P7; n = 2, mean ± range — sub-table below; text: release 40% at the start, ≈60% when S was reduced to 2.6 after 75 min, then constant at 60−65%; 2 µg/mL when S was decreased to 1, against a crystalline solubility of 3.6 µg/mL | Fig. 6, p.3494 |
| R19 | record, measured | lopinavir concentration vs time, lopinavir–SBA-15 25% w/w — P6; buffer pH 6.8; dosed at the lopinavir amorphous solubility (16.4 ± 0.1 µg/mL, M2) and at half of it; n = 3, mean ± SD — 100%: ≈7.7 (5 min), ≈7.7 (15), ≈7.6 (30), ≈7.8 (60), ≈7.4 (90), ≈6.7 µg/mL (120); 50%: ≈4.3, ≈4.5, ≈4.8, ≈4.9, ≈4.9, ≈5.7 µg/mL (SD ≈1.5 at 120 min) (read from Fig. S1); right axis: 100% dose ≈47% at 5 min and ≈41% at 120 min, 50% dose ≈52% at 5 min and ≈70% at 120 min (read from Fig. S1); text: 100% ≈7−8 µg/mL, 40−50% release; 50% ≈60% release | Fig. S1, SI p.2; text p.3494 |
| R21 | record, measured | ritonavir concentration vs time in FaSSIF — P6 in FaSSIF; dosed at the FaSSIF amorphous solubility (43 µg/mL); n = 3, mean ± SD — ≈25.4 (5 min), ≈27.7 (15), ≈29.0 (30), ≈30.1 (45), ≈30.4 (60), ≈31.5 (90), ≈30.2 µg/mL (120) (read from Fig. 7); text: 25 µg/mL at 5 min, ≈30 µg/mL after 30−45 min, constant thereafter; release stabilized at ≈71%, against ≈50% in buffer (p < 0.05) | Fig. 7, p.3495 |
| C2 | claim, conclusion, authors: asserted ("always"; "Importantly") | Supersaturated ritonavir solutions were generated from ritonavir-loaded SBA-15, but release was always incomplete, even under sink conditions, and under all dissolution conditions investigated [rests on: R6, R18, R21, R22] | p.3489, p.3495 |

## 2019 Dening — Application of an adsorption isotherm to explain incomplete drug release from ordered mesoporous silica materials under supersaturating conditions · Mesoporous silica / Mesoporous silica

[2019-dening-adsorption-isotherm-incomplete-release-sba15](../../../cards/2019-dening-adsorption-isotherm-incomplete-release-sba15/paper.html) · Mesoporous silica / Mesoporous silica · measured · as: incomplete drug release

| id | kind | content | locator |
|---|---|---|---|
| R16 | record, cited (ref 6) for % release; derived (relation not printed) for adsorbed amount | sequential-dilution release and ritonavir remaining adsorbed — P10; n = 2, mean ± range — sub-table R16 a–f (read from Fig. 8); text: release ≈40% at start, 60% after 75 min (theoretical S 2.6), no further change; remaining adsorbed ≈170 mg/g after 15 min, 100–110 mg/g from 75 min on; Qm line at 103 mg/g | Fig. 8 and Section 4.8, p. 193; Section 5.3, p. 197 |
| R17 | record, measured; surfactant-free column cited (ref 6) | ritonavir concentration vs time with monomeric surfactants — P9; dose 28 μg/mL; mean ± SD, n = 3 — sub-table R17 a–g (read from Fig. 9); text: Vit E TPGS 15 → 17 μg/mL over first 30 min, maximum 61% release; surfactant-free maximum 14 μg/mL, 50% release, equilibrium after 5 min; Vit E TPGS vs surfactant-free at 30 min p < 0.05; Vit E TPGS concentration falls from 45 min and reaches approximately the crystalline solubility (within experimental error) at 120 min; SDS equilibrium after 45 min, release 40% at 5 min to approximately 50% after 2 h, maximum 14 μg/mL; SDS vs surfactant-free maximum p > 0.05 | Fig. 9, p. 193; Section 4.8, pp. 193–194 |
| R19 | record, derived (relation not printed) | ritonavir remaining adsorbed to SBA-15 at maximum release — P9; 120 min (buffer, SDS) or 30 min (Vit E TPGS media); mean ± SD, n = 3 — sub-table R19 a–d; text: above Qm in buffer and SDS media, below Qm in both Vit E TPGS media; micellar Vit E TPGS vs buffer and vs monomeric Vit E TPGS p < 0.05 | Section 4.8, p. 194; Section 5.3, p. 197; Fig. S6, SI p. 7 |
| C1 | claim, generalisation, authors: asserted | Earlier work showed incomplete drug release to be a constant feature of OMS formulations under supersaturating conditions, persisting even when diluted towards sink conditions. [rests on: cited: refs 3, 6, 12–18] | Abstract, p. 186; Section 1, p. 187; Section 5.1, pp. 194–195 |
| C32 | claim, conclusion, authors: asserted ("It becomes obvious"; "clearly demonstrates"; "excellent correlation") | On sequential dilution release plateaued at ≈60% after 75 min despite favourable conditions, leaving 100–110 mg/g adsorbed, equal to Qm; the excellent correlation shows ritonavir adsorption to OMS is partially irreversible and release stops at monolayer adsorption. [rests on: R16, R6] | Section 4.8, p. 193; Section 5.3, p. 197; Section 6, p. 198 |

## 2020 Hate — Interplay of Adsorption, Supersaturation and the Presence of an Absorptive Sink on Drug Release from Mesoporous Silica-Based Formulations · Mesoporous silica / Mesoporous silica

[2020-hate-atazanavir-mesoporous-silica-adsorption-absorptive-sink-release](../../../cards/2020-hate-atazanavir-mesoporous-silica-adsorption-absorptive-sink-release/paper.html) · Mesoporous silica / Mesoporous silica · measured · as: incomplete drug release

| id | kind | content | locator |
|---|---|---|---|
| R15 | record, derived (E4) | total drug release (%) — as R13 — sub-table below; text: 5 and 10% approximately 80%; 20% 66% after 90 min; 25–30% released instantaneously for 5, 10, 20%; 30% released 50% in 90 min; 50% maximum 35% (p.11); 5% DL 30% burst, 50% DL negligible burst (p.14) | Fig. 8c, p.10; text p.11, p.14 |
| R20 | record, derived (E4) for dissolution-absorption; measured for closed compartment | total drug release (%) with and without the absorptive compartment — 20% DL ATZ-MPS, dose 75 µg/mL, pH 6.8; dissolution-absorption (P9) versus closed compartment (P7), 240 min — sub-table below; text: dissolution-absorption released constantly, reaching almost 90%; closed compartment only 40%, plateau after 60 min (p.13); "plateaued at 40%" versus "90% release" (p.15) | Fig. 10c, p.11; text p.13, p.15 |
| C5 | claim, mechanism, authors: abstract: "largely due to"; results: "can likely be partially attributed" | Incomplete release is largely (abstract) or partially (results) caused by the adsorption tendency of ATZ onto silica [rests on: R15, R2] | p.1, p.11 |
| C43 | claim, conclusion, authors: asserted ("it is apparent") | The amount of ATZ remaining in the silica after dissolution was much greater than expected from the adsorption isotherm, especially for higher DL [rests on: R2, R15] | p.14 |

## 2020 Hate — Influence of Drug-Silica Electrostatic Interactions on Drug Release from Mesoporous Silica-Based Oral Delivery Systems · Mesoporous silica / Mesoporous silica

[2020-hate-drug-silica-electrostatic-interactions-mesoporous-release](../../../cards/2020-hate-drug-silica-electrostatic-interactions-mesoporous-release/paper.html) · Mesoporous silica / Mesoporous silica · measured · as: incomplete drug release

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured | KET release from 20% DL KET-MPS (total drug release %, mean ± SD, n = 3) — P5; target 50 µg/mL; 50 mL, 37 °C — sub-table below; text: immediate and almost complete release (80-90%) at pH 1 and 4.5; release substantially reduced at pH 5.5 and 6.8 | Fig. 4a, p.14; text p.13 |
| R8 | record, measured | CLZ release from 20% DL CLZ-MPS (as R7) — P5; target 150 µg/mL — sub-table below; text: rapid and complete release at pH 1 and 4.5, slight reduction at pH 5.5, considerably lowered release at pH 6.8 | Fig. 4b, p.14; text p.13 |
| R9 | record, measured | ATZ release from 20% DL ATZ-MPS (as R7) — P5; target 75 µg/mL — sub-table below; text: burst release of 70% at pH 1 and no further release over 60 min; at pH 4.5, 5.5 and 6.8 a burst of 10-20% and a plateau at about 40% after 60 min | Fig. 4c, p.14; text p.14 |
| C49 | claim, generalisation, authors: asserted | Adsorption was higher when the drug interacted with silica by electrostatic interaction than by hydrogen bonding, and higher adsorption led to a lower extent of release [rests on: R3, R4, R5, R7, R8, R9, R14] | p.3 |

## 2020 Mccarthy — A Comparison of Drug Release and Adsorption Under Supersaturating Conditions for Ordered Mesoporous Silica with Indomethacin or Indomethacin Methyl Ester · Mesoporous silica / Mesoporous silica

[2020-mccarthy-indomethacin-indme-sba15-adsorption-release](../../../cards/2020-mccarthy-indomethacin-indme-sba15-adsorption-release/paper.html) · Mesoporous silica / Mesoporous silica · measured · as: incomplete drug release

| id | kind | content | locator |
|---|---|---|---|
| R20 | record, measured | non-sink dissolution of 50% monolayer formulations (µg/mL, mean, n = 3; error bars "too small to be visible") — P14; dose 35.1 µg/mL (IND), 9.0 µg/mL (INDME) — sub-table below (≈, read from Fig. 11); text: burst release to a supersaturated solution at 5 min; IND release "peaked at 5 min"; INDME increased until 30 min, then plateaued; Cmax 16.6 µg/mL (IND) and 2.9 µg/mL (INDME); 45% and 35% release; Cmax over equilibrium solubility 7.2 (IND) and 7.0 (INDME); right-hand % axes of Fig. 11 put 100% at ≈40 µg/mL (IND) and ≈9.5 µg/mL (INDME), giving ≈41% and ≈31% at Cmax | p.29; Fig. 11, p.30 |
| R23 | record, measured | drug retained in the recovered solid (% of dose, mean ± SD, n = 3) — P14 — IND 58.8 ± 6.6%; INDME 61.8 ± 6.8%; stated to account for 103% of the IND dosed and 94% of the INDME; drug loading of the harvested solid approximately 60% of the initial loading for both drugs | p.30-31 |
| C52 | claim, mechanism, authors: conclusion: "can be rationalized"; abstract: "was, in turn, found to limit"; "provides an explanation" | The incomplete release can be rationalized by the strong tendency of each compound to adsorb to mesoporous silica from water, particularly from highly supersaturated solution; the abstract states that this adsorption was found to limit release under non-sink conditions and explains incomplete release [rests on: R7, R8, R12, R20, R23, R24, R26] | p.2, p.40 |