# Evidence: hierarchical particle approach

Parent: — · class: formulation design · names merged here: hierarchical particle; hierarchical particle approach

2 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.

## 2023 Hiew — Improving Dissolution Performance and Drug Loading of Amorphous Dispersions Through a Hierarchical Particle Approach · Dissolution / A. Release mechanism and LoC

[2023-hiew-grazoprevir-hierarchical-cpad-surface-drug-release](../../../cards/2023-hiew-grazoprevir-hierarchical-cpad-surface-drug-release/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: hierarchical particle

| id | kind | content | locator |
|---|---|---|---|
| C7 | claim, conclusion, authors: asserted | The additional polymer in the anti-solvent was deposited on the cPAD particle surfaces during isolation and drying, creating hierarchical particles (a core ASD particle with an additional water-soluble component coating its surface) [rests on: R6, R14] | p.2057 |
| R10 | record, measured | two-stage dissolution of binary and 0.001 N HCl hierarchical cPADs (% of dose released) — P6 rows a, b, d, e, j; P12 — sub-table below; 0-30 min ≈0-1% for all (read from Fig. 3); text: both binary cPADs below 50% of the 150 µg/mL dose; with HPMC pre-dissolved in the anti-solvent >60% at 90 min; washed sample ~47% | Fig. 3, p.2063; text p.2062 |
| R14 | record, measured | XPS surface grazoprevir concentration (%) against release at 90 min (%) and bulk DL as plotted (%) — P14 (surface concentration mean ± SD, n = 5), P12; seven cPADs and SE20 — sub-table below; text: B-75-MTBE/RE60 ~84%, B-75-HCl/FD ~53%; SE20 and H-HPMC-HCl/RE60 both release ~63% at 90 min | Fig. 7, p.2066; text p.2064 |
| R15 | record, measured | pharmacokinetic parameters after 100 mg capsules in dogs — P15, P16, P17; n = 6 — sub-table below | Table 5, p.2066 |
| C54 | claim, conclusion, authors: asserted ("was shown") | Grazoprevir-HPMCAS hierarchical cPAD was shown to release better than binary cPAD; hierarchical cPADs with different external polymers and anti-solvents gave informative release patterns [rests on: R10, R11, R12] | p.2067 |

## 2025 Hiew — The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations · Dissolution / A. Release mechanism and LoC

[2025-hiew-surface-composition-wettability-high-drug-loading-asd](../../../cards/2025-hiew-surface-composition-wettability-high-drug-loading-asd/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: hierarchical particle approach

| id | kind | content | locator |
|---|---|---|---|
| P6 | method | anti-solvent co-precipitation, hierarchical cPAD with HPMC (rotor–stator) | p.291-292 |
| P7 | method | anti-solvent co-precipitation, hierarchical cPAD with non-HPMC excipient | p.292 |
| R22 | record, cited | earlier grazoprevir cPAD results — ref 29 (Hiew 2023) — co-precipitation with HPMC as secondary polymer gave grazoprevir dispersions up to 70% DL with good in vitro release and in vivo bioavailability; in vitro release was a very good predictor of in vivo pharmacokinetics; hydroxypropyl cellulose as secondary polymer did not give similar results | p.290, p.296 |
| C11 | claim, recommendation, authors: abstract: "promising"; conclusion: "promising strategy" | The hierarchical particle approach, with judiciously chosen secondary excipients, is a promising strategy to formulate high DL amorphous dispersions with good wettability and improved dissolution [rests on: R9, R10, R17] | p.289, p.302 |