Why does an API remain amorphous during storage, yet fail to release as expected during dissolution? These questions share a common starting point: the interactions between the API, polymer and water.
Amorphous solid dispersions (ASDs) offer a way to improve the dissolution of poorly soluble drug substances. Their development requires decisions about polymer selection and drug load, followed by suitable manufacturing and storage conditions. Experimental screening provides essential evidence. Thermodynamic modelling helps explain that evidence and identify which experiments are most useful next.
What an ASD phase diagram tells us
A binary API/polymer phase diagram connects composition and temperature. The crystalline solubility boundary shows how much API the polymer can accommodate at equilibrium at a given temperature. When the drug load exceeds that solubility, crystallization becomes thermodynamically favourable. Whether crystallization occurs during a relevant observation period also depends on kinetics.
The glass transition adds another part of the picture. Below the mixture’s glass-transition temperature, reduced molecular mobility can slow crystallization substantially. An ASD can therefore remain physically stable over a useful period even when it is supersaturated. A phase diagram helps distinguish this kinetic stabilization from thermodynamic stability. It can also identify a tendency for the amorphous mixture to separate into API-rich and polymer-rich phases.
Manufacturing: dissolution below the API melting point
For hot-melt extrusion, the neat API melting point does not alone define the temperature required to form an ASD. The API may dissolve in the softened polymer below that melting point. Predicted solubility and glass transition help identify a temperature range worth investigating experimentally.
The usable process window also depends on residence time, mixing and shear, viscosity, and the thermal stability of both components. Modelling can narrow the candidate space, while experiments establish whether the selected conditions produce the intended formulation.
Water changes the formulation during dissolution
During dissolution, the dry ASD takes up water and its composition changes. A ternary API/polymer/water phase diagram makes this hydration path visible. It helps explain which phases can coexist and how the API and polymer partition between them.
This matters when increasing drug load changes the release mechanism. The API and polymer may initially release together, but above a critical composition their release can become incongruent. API-rich phases or crystallization can then contribute to poor release. Phase diagrams provide a framework for investigating such behaviour. They do not, by themselves, predict the time required for phase formation or crystallization.
Why HPMCAS grade selection matters
HPMCAS grades differ in their acetyl and succinyl substitution ratios. Those differences affect their interactions with the API and water. Consequently, the release and precipitation-inhibition behaviour of one grade cannot simply be transferred to another.
In suitable systems, a polymer-rich phase can accommodate dissolved API and act as a reservoir. Understanding this phase behaviour helps explain why a formulation maintains supersaturation or loses it. The most appropriate grade depends on the particular API and the intended formulation conditions.
What you will learn in the webinar
In Amorphous Solid Dispersion Vol. 2: The Mystery Finally Solved, Dr. Christian Lübbert will connect these mechanisms to formulation examples, with Dr. Christian Nowak moderating. Participants will learn how to read ASD phase diagrams, assess polymer and drug-load choices, identify HME conditions for experimental evaluation and interpret dissolution behaviour, including differences between HPMCAS grades.
- Read ASD phase diagrams to guide polymer selection and drug load.
- Distinguish thermodynamic stability from kinetic stabilization.
- Understand dissolution versus melting during hot-melt extrusion.
- Interpret hydration paths and loss of congruent release.
- Explain differences in release and precipitation inhibition between HPMCAS grades.
Wednesday, 21 October 2026, 10:30–11:30 CEST · Free online webinar
