Dissolution of medicines formulated as amorphous solid dispersions, FHNW School of Life Sciences

Some medicines do not dissolve well in the body, meaning they can’t be properly absorbed and do not provide their desired therapeutic effects. To overcome this problem, these drugs can be formulated as amorphous solid dispersions (ASD). In ASDs, a drug’s crystal-based molecular structure is chemically converted into an amorphous structure and dispersed using a solid polymer carrier.

This formulation strategy works well up to a given point. When larger quantities of a drug substance are loaded into the formulation, it may not dissolve alongside the polymer, recrystallising and leading to erratic release. This point is known as the limit of congruency (LoC), and it’s crucial to identify especially in formulations where a greater amount of the drug is needed.

In collaboration with Nisso Chemical Europe, our team developed a new test that measures intrinsic dissolution of medicines formulated as amorphous solid dispersions using Nisso’s hydroxypropyl cellulose (HPC) as the carrier.

In higher concentrations of drug substance (30% or more), it’s desirable to use HPC plus other additives in the formulation, to increase drug stability and release. We developed computational tools to predict ideal ratios of different drugs + carriers + additives.

Finally, we are now working with Nisso on the possibility of formulating a new class of molecules called proteolysis-targeting chimeras (PORTACs) using HPC. PORTACs combine some properties of small molecules and biologics, and like biologics, are challenging or impossible for oral delivery. Building on work we did as part of the Horizon Europe project FASS, our aim is to enable these new medicines to be taken orally and be absorbed by the body.

• Guiding excipient selection for physically stable amorphous solid dispersions: A combined in-vitro in-silico approach
• Guiding excipient selection for amorphous solid dispersions by combining an in vitro-in-silico approach – II: Supersaturation and drug release