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Three ways through the library, a reading order, the questions a newcomer asks and the conclusions.

Dissolved drug concentration, high to low

The splitting of a highly supersaturated aqueous drug solution into a water-rich continuous phase and a dispersed, non-crystalline drug-rich phase, before crystals form.

Amorphous solubility

The concentration of dissolved drug at which a supersaturated aqueous solution is in apparent, metastable equilibrium with the amorphous drug, more rigorously with the water-saturated supercooled liquid or glass.

Between the two: supersaturation

A solution concentration above the crystalline solubility of the drug.

Crystalline solubility

The equilibrium solubility of the stable crystalline form of the free drug in a given medium, the reference against which supersaturation and the amorphous advantage are defined.

Start at your level

Three ways through the same library.

Starting out · 5 minutesWhat an ASD isWhy a drug is made amorphous, what the dispersion does in solution, and three ways it can fail.Read the introduction → Formulating · 30 minutesHow to think about a formulationThe main findings in order: the amorphous solubility, drug loading, polymers and thresholds, and exposure in animals.Follow the path → Going deep · 20 minutesWhy dispersions crystallizeDriving force, mobility, nucleation and growth, phase state and water, with what is measured and what is proposed.Read the mechanisms →

The 30-minute path

In this order.

1
The idea in one column
The four concentrations at the top of this page.
2 min
Read it →
2
How the parts fit together
One amorphous drug followed from the solid to the membrane.
5 min
Overview →
3
The 14 conclusions
What the library concludes across all categories, in single sentences.
3 min
Read them →
4
What happens at the ceiling
Past the amorphous solubility a solution splits and the free drug stops rising.
8 min
Solution splits → Free drug stops rising →
5
What drug loading does
One loading step changes how the dispersion releases.
4 min
Loading step →
6
Polymers and thresholds
What a polymer acts on, and why each loading threshold is a different quantity.
5 min
Polymers → Thresholds →
7
Does it work in an animal
Exposure in rats against the amorphous solubility.
3 min
Rat exposure →

Questions

Open a question to see where the wiki answers it, in reading order.

1What is an ASD, and why make one?

PageWhat an ASD is, in 5 minutes
Termamorphous solid dispersionA drug dispersed in a polymer in the amorphous state to raise dissolution rate and supersaturation.
Termamorphous solubility advantageThe factor by which the amorphous drug is more soluble than the crystal, $e^{\Delta G/RT}$ from the crystal–amorphous free-energy difference, reduced by the activity of the water-saturated amorphous drug.
TermsupersaturationA solution concentration above the crystalline solubility of the drug.
PageHow the parts fit together

2What are crystalline solubility, amorphous solubility and supersaturation?

Termcrystalline solubilityThe equilibrium solubility of the stable crystalline form of the free drug in a given medium, the reference against which supersaturation and the amorphous advantage are defined.
Termamorphous solubilityThe concentration of dissolved drug at which a supersaturated aqueous solution is in apparent, metastable equilibrium with the amorphous drug, more rigorously with the water-saturated supercooled liquid or glass.
TermsupersaturationA solution concentration above the crystalline solubility of the drug.
C. Amorphous solubility and LLPS · F1Past a certain concentration, a supersaturated drug solution splits into drug-rich droplets before any crystal appears.
C. Amorphous solubility and LLPS · F8Past the limit, extra drug only adds drug-rich phase; the free drug, its activity and the membrane flux stay level.
PageTaylor and Zhang 2016 followed step by step

3Why does the amorphous form crystallize, and what slows it?

PageWhy dispersions crystallize: the mechanisms
Termthermodynamic driving force for crystallizationThe free-energy difference between the supercooled liquid (amorphous form) and the crystal, written ΔGv per unit volume or ΔG per mole or gram.
Termmolecular mobilityHow fast molecules of an amorphous solid move and rearrange, the kinetic side of crystallization next to the driving force.
Overview · F4The crystallization class of the neat drug orders drugs within one test, but carriers, routes and polymers override it.
Overview · F5Polymers slow nucleation far more than growth, so crystals already present bypass them, and rankings do not transfer.
Solid state stability · F4A polymer can slow growth without lowering nucleation, so a polymer ranking holds only for the step measured.
Solid state stability · F7A few percent polymer removes most nucleation, but the drug loading must stay below the miscibility limit.

4What does a polymer do, and how do I choose one?

5How does drug loading matter?

Termdrug loadingThe weight fraction of drug in an ASD (10, 30, 50% in the earlier papers).
Overview · F8Every category has a drug-loading threshold, but storage, release, absorption, silica and peptide thresholds are different quantities.
Dissolution · F7One loading step switches a dispersion from release with the polymer to a drug-rich layer and little release.
Solid state stability · F7A few percent polymer removes most nucleation, but the drug loading must stay below the miscibility limit.

6What is liquid-liquid phase separation, and why does it matter?

Termliquid-liquid phase separationThe splitting of a highly supersaturated aqueous drug solution into a water-rich continuous phase and a dispersed, non-crystalline drug-rich phase, before crystals form.
C. Amorphous solubility and LLPS · F1Past a certain concentration, a supersaturated drug solution splits into drug-rich droplets before any crystal appears.
C. Amorphous solubility and LLPS · F8Past the limit, extra drug only adds drug-rich phase; the free drug, its activity and the membrane flux stay level.
Bioperformance · F2Above the amorphous solubility, adding more drug no longer raises the flux across a membrane.
Bioperformance · F5Tiny drug-rich droplets keep the flux at its maximum for longer; coarse amorphous particles do not.

7What happens when an ASD dissolves?

8How do storage temperature and humidity affect it?

PageWater acts by two routes
Termplasticization by waterThe lowering of the glass transition temperature of an amorphous drug by absorbed water, taken in these papers as about 10 °C per 1% water.
Overview · F9Water separates drug and polymer during manufacture, storage and wetting; the separation raised release in one system and lowered it in another.
Solid state stability · F9In humid storage the best polymer depends on the drug: PVP loses its advantage for felodipine but not for polyphenols.
Solid state stability · F10The drug's affinity for water, not log P or melting data, set what sorbed water did in PVP and in PEO.
Solid state stability · F11A free surface, a crystalline carrier, quenched-in nuclei, the drying route or trapped water can outweigh the formulation.
Solid state stability · F12A stability test ranks only inside a window: the protocol sets the class and the stress changes the route.

9How is an ASD made, and what can go wrong?

10How do I measure crystallinity, miscibility and phase behaviour?

11Does an ASD work in vivo, and how do I test that in vitro?

12If I had to make one for a new drug, what are the steps?

The wiki has no single ordered procedure. The closest material is the “For your drug” block of each finding, and the design target at the end of a review.
PageThe 14 conclusions, each with “For your drug”
PageTaylor and Zhang 2016, step 10: the design target

The 14 conclusions

What the whole library says when the categories are read together. Underlined words show a definition; F numbers open the evidence.

F1In every category free drug and membrane flux stop at the amorphous solubility, and formulations are judged by reaching it.
F2A second drug, a polymer or a bile salt that mixes into the drug-rich phase lowers the amorphous solubility.
F3Near the amorphous solubility and in micellar media, total drug misleads; free drug or flux has to be read.
F4The crystallization class of the neat drug orders drugs within one test, but carriers, routes and polymers override it.
F5Polymers slow nucleation far more than growth, so crystals already present bypass them, and rankings do not transfer.
F6Residual crystals cost supersaturation from the extruder to the animal; a crystallized tacrolimus capsule lost about half its exposure in dogs.
F7Whether a sample is amorphous depends on the method; crystals below the X-ray limit changed dissolution.
F8Every category has a drug-loading threshold, but storage, release, absorption, silica and peptide thresholds are different quantities.
F9Water separates drug and polymer during manufacture, storage and wetting; the separation raised release in one system and lowered it in another.
F10A dispersion can crystallize inside its wetted solid before the drug dissolves; a dissolved polymer does not prevent this.
F11No polymer was best at every stage: fast release and thermal protection favoured PVP or PVPVA, inhibition and humid storage HPMCAS.
F12Surfactants raised release in every category, and in every category they also promoted crystallization or gave no final gain.
F13The gastric stage, the pH shift, the medium and food changed the outcome for every carrier.
F14Flux and absorptive tests tracked animal exposure better than closed vessels, but animal data cover three drugs and no human dispersion.

Other ways in

Glossary and searchEvery term, abbreviation and formula, and a search through all findings. Drugs and polymersEvery property value the papers give, per material.

Three reviews, read closely

Solute activity from crystalline solubility to absorption: the amorphous ceiling, the drug-rich reservoir and the design target

Its argument, step by step → · equations →

Crystals in amorphous solid dispersions: where they come from, what they change in release, and how a limit is set

Its argument, step by step → · equations →

The amorphous solubility as the limit of supersaturation: from the free-energy calculation, through additives and measurement, to the dose number

Its argument, step by step → · equations →