How amofor Reduces Drying Times by up to 50%

The Challenge

Spray-drying is a well-established method to produce amorphous solid dispersions (ASDs). However, after spray drying, a considerable amount of residual solvent remains trapped inside the polymer matrix. These solvents must be removed during secondary drying to comply with regulatory limits (e.g., ICH thresholds of <600 ppm for dichloromethane) and to ensure physical stability

Traditional secondary drying methods, such as vacuum drying, can take several days. The bottleneck is the slow diffusion of solvent molecules through the dense, amorphous matrix – a process that is inherently inefficient and time-consuming.

Conventional Strategies and Their Limitations

To accelerate solvent removal, pharmaceutical manufacturers often employ:

• Higher drying temperatures and stronger vacuum

• Nitrogen sweeps to lower the solvent partial pressure

• Secondary solvents such as water or methanol to enhance diffusion and evaporation

While effective to some degree, these methods usually require extensive Design of Experiments (DoE) campaigns to identify the best process parameters. This consumes both time and material resources.

amofor’s Predictive PC-SAFT Approach

At amofor, we apply our PC-SAFT (Perturbed Chain Statistical Associating Fluid Theory) thermodynamic model to transform how secondary drying is designed.

Instead of relying on trial-and-error experiments, we simulate drying scenarios in silico. Our predictive modeling can answer key process questions upfront:

• How do temperature, pressure, and nitrogen sweep rates affect drying speed?

• What is the impact of using water or methanol as assisting solvents?

• How quickly can a specific residual solvent be removed under given conditions?

Our simulations produce drying curves, time-dependent Tg profiles, and virtual process maps, giving formulators direct insight into drying kinetics and crystallization risks.

The Benefits for Our Clients

• 50% faster drying: Drying times are cut from several days to hours.

• Regulatory confidence: Solvent levels are predictably reduced below ICH limits.

• Elimination of costly DoE trials: Predictions replace experimental screening.

• Optimized use of secondary solvents: PC-SAFT shows in advance which solvent combinations maximize diffusion and evaporation

For example, in one client project, we modeled the secondary drying of a HPMCAS-based ASD containing dichloromethane. Conventional vacuum drying would have required over two days. By simulating nitrogen-assisted drying, we demonstrated that complete solvent removal could be achieved within hours – exactly as the subsequent lab validation confirmed.

With PC-SAFT-based predictive modeling, amofor makes secondary drying faster, safer, and scientifically justified. Our approach enhances process efficiency while safeguarding product quality and stability – all without the need for lengthy experimental trials.

Learn more about this technique in our blog article: