True Density Measurement
Non-destructively measure internal density with digiM’s proprietary method, built to study batch uniformity and stability impact on product quality
Measure the internal true density of drug products for microstructure assessment
Our true density measurement is a patent-pending method for quantification of material true densities and quantitative comparisons of drug product microstructure arrangement (US20240003797A1). Built for X-ray micro-CT and X-ray microscopy scans using specialized algorithms and a custom calibration system, the technique enables true density calculation for each and every sample in a scan, whether it be a couple tablets or hundreds of microspheres. With this approach, sub-resolution variations in porosity, ingredient distribution, and ingredient changes after aging and stability be quanitatively evaluated.
Batch Equivalence and Uniformity
Intra-batch or inter-batch equivelance assessment, including representativeness analysis for higher resolution studies like FIB-SEM.
Aging and Stability Impact on Quality
Determine the impact of aging and ICH stability testing on microstructure quality, with insight into porosity, polymer behavior, and ingredient movement.
Sub-Resolution Features
Quantify structures which are difficult to to capture, such as sub-resolution porosity impact on density.
Rapidly Assess for Product Quality
Get fast, interpretable feedback on density-related CQAs to support regulatory submissions and demonstration of robust product quality.
Traditional density measurements like bulk density and pycnometery work well for routine analytical testing. However, these techniques cannot "see" how the density is associated with formulation constituents and the impacts of manufacturing steps like drying and compression. This is a gap in understanding the relationship of matrix density with ingredient interactions and their porosity, which are critical for drug release. Our density measurement method bridges this blind spot through 3D imaging, offering true, localized density measurements across the entire product, without disrupting its structure. It’s a modern solution to a longstanding problem in pharmaceutical development.
How it Works
In X-ray micro-CT imaging, subtle differences in the grayscale intensity of pixels are correlated to the X-ray attenuation by different material domains and void spaces. This attenuation is related to the material true densities and their elemental composition. In a matrix-based system, when these subtleties in grayscale pixels are sub-resolution, they can be difficult to classify and quantify. Applying a workflow with a calibrant system and specialized algorithms, our density measurement enables density calculation for each sample in the scan (eg each microsphere). For larger products like tablets and implants, density can be measured as a spatial distribution, understanding how microstructures are impacted by the manufacturing operation.
Insight to Impact
For stability studies, batch scale ups, and formulation tuning, internal density assessment of microstructure can be paramount in dissolution optimization. With our calibrated density platform, teams have uncovered hidden structural changes that standard methods overlook. In the use case shown here, our density measurement reveals a drop in density when comparing fresh vs aged microsphere batches. Validated and assessed with further detail via FIB-SEM, the change was found to be associated with an increase in nanoporosity and shift of the polymer over time. The insights are fast, visual, and actionable, enabling formulation scientists, CMC teams, and regulatory scientists to gain deeper knowledge about their product.
Our density measurement system is available as a module through digiM I2S, for contract research projects, or via licensing pathways.
Revolutionizing Development Strategies
Connect with our team to see how density mapping can uncover hidden changes and support critical decisions.
