Powder Drying Optimization: Turning an Overlooked Unit Operation into a Source of Speed, Stability, and Predictability

Drying is often treated as a bottleneck in drug-substance development. This operation is one of the single biggest determinants of cycle time, form stability, solvent clearance, and downstream performance. Most problems that appear during scale-up can be prevented far earlier, through decisions around washing strategy, solvent selection, and particle-size control.

APC’s Powder Drying Optimization platform reframes drying as a controllable design variable, integrating solid-state analytics, process engineering, and predictive modeling to deliver predictable, scalable outcomes.

Why Drying Fails at Scale

Binary solvent effects, form instability, agglomeration or attrition, and undefined scale-down rules, are persistent challenges that cause schedule risk and variability.

These issues persist because drying is rarely characterized with the same rigor as crystallization or filtration.

Our Approach

A three-platform workflow provides an end-to-end scientific view of drying behavior, enabling confident decisions from milligram quantities through pilot scale.

1. Map Kinetics & Critical Points

Dynamic Vapor Sorption (DVS)

• Defines drying curves and solvent–surface interactions

• Identifies critical moisture content (Xc)

• De-risks single/binary solvent systems

• Requires minimal material andeliminates guesswork early

2. Confirm Regimes & Endpoints

Tray Dryer Studies

• Distinguish constant-rate vs falling-rate regimes

• Track solvent-removal pathways

• Check form stability through the cycle

• Offer observable kinetics and direct sampling

3. Replicate Plant Conditions & Stress-Test Scale-up

Agitated Filter-Dryer (AFD) Experiments

• Control agitation, temperature, and pressure

• Use hydrostatic-pressure and sticky-point tests to avoid attrition/agglomeration

• Establish operating envelopes that translate directly to the plant

These insights feed predictive tools (VLE, Dynochem, gPROMS) and are visualized via APC’s drying model web application to set explicit equivalence criteria for transfer.

Impact Across Development

Form Control

Hydrates and solvates remain stable when drying conditions are matched to their stability windows. DVS and non-ambient PXRD define the safe zone; RH/temperature profiles preserve the desired form or intentionally drive transformation.

Cycle-Time Compression

Optimizing particle size, washing strategy, and solvent interactions shortens drying phases and transforms an unpredictable hold time into a short, reliable step.

Residual Solvent Clearance

By characterizing solvent–solvent interactions and desorption mechanisms, binary systems can be cleared 2× faster while expanding the quality margin.

Particle Integrity

AFD-based stress testing ensures agitation strategies prevent agglomeration or attrition, maintaining the PSD needed for downstream processing.

Robust Tech Transfer

Clearly defined instructions around parameters such as cake depth, pressure, RH/temperature trajectory, agitation and sampling enable first-pass success and reduce transfer timelines by multiple weeks.

Case Study: Cutting Cycle Time from 81 to 48 Hours

A late-phase intermediate exhibited drying times exceeding 81 hours with poor residual solvent clearance, PSD drift, and batch-to-batch variability - issues that escalated during scale-up.

APC’s digitally led redesign produced major gains:

• 41% shorter cycle time: Drying reduced from 81 to 48 hours via targeted wash optimization and improved particle-size control.

• 69% lower residual solvent: Binary-solvent removal accelerated significantly.

• Hydrate retention: Form maintained consistently across pilot batches.

• Improved consistency: RSD reduced by 66%; downstream recovery increased by 50%.

• Higher yield: Overall product yield increased by 15%.

Embedding drying science early converted an unreliable bottleneck into a predictable, data-driven operation that transferred seamlessly from lab to plant.