AAPS PharmSci 360: Microstructure Intelligence in Predictive Drug Development, Part 2

In part 2 of this 2-part preview of AAPS PharmSci 360’s keynote on predictive drug development, Robert Holt, PhD, associate director, Pharmaceutical Science, digiM Solution, provides examples of how microstructure intelligence compresses development timelines and strengthens regulatory filing, particularly for modern, complex products such as long acting therapies, oral peptides, and combination products.

Holt explains that microstructure data delivers value at each development stage, such as feasibility and screening, baseline scans for calculating critical quality attributes from minimal material, and informing early formulation decisions. During optimization, these tools link particle structure to dissolution and release performance, enabling in silico formulation tuning. At scale-up and tech transfer, platforms like digiM’s dissoLab and ivisLab run mechanistic simulations that stress-test manufacturing variations in minutes, reducing batch-failure risk and generating physics-based data packages for regulators.

Providing an example of the value of microstructure data, Holt shares a case study where a major pharma client saw a dissolution slowdown between lab-scale and good manufacturing practice (GMP) batches of spray-dried dispersions, despite conventional characterization (laser diffraction, mercury injection, BET, XRPD) showing the batches as comparable. X-ray microscopy combined with artificial intelligence (AI) image analysis revealed the real cause: the GMP batch had stronger aggregation from droplet merging, cutting particle surface area by 40% versus the lab batch's looser, electrostatic aggregation.

When asked about this technology’s future, Holt notes that digiM holds an FDA IDIQ contract for regulatory assessment and guideline development on complex drug products, and its work informed product-specific guidelines for minocycline microspheres and dexamethasone ophthalmic implants, with the FDA encouraging microstructural characterization for generics. Holt calls digiM “the first FDA-recognized microstructure platform for drug product development,” positioning the technology as an emerging pillar of quality-by-design and real-time release strategies, with new AI tools that generate 3D drug substance and product models from 2D images.

Looking ahead to AAPS PharmSci 360 in New Orleans, Holt says the keynote his company is presenting will explore imaging science, predictive science, and AI applications for emerging modalities, such as long-acting injectables, high-concentration biologics, and combination products, where microstructure intelligence is poised to address next-generation manufacturing challenges.

AAPS PharmSci 360 is happening in New Orleans from October 25-28, 2026.

Click the video above to watch the interview.

Click here to watch part 1.