Particle Characterization

Measuring what matters — because the size of a particle defines the performance of a drug.

Particle Characterization

In the pharmaceutical industry, particle characterization is the cornerstone of successful particle engineering, serving as the critical verification tool to confirm that micronization or milling processes have achieved the target Particle Size Distribution (PSD). Because the physical dimensions of drug particles directly impact on biopharmaceutical performance precise measurement is essential for transitioning a NCE from synthesis to clinical formulation.

The Biopharmaceutical Rationale

The fundamental rationale for rigorous particle characterization is the direct correlation between a drug’s Particle Size Distribution (PSD) and its clinical performance, established through the definition of Critical Quality Attributes (CQAs) within a Target Product Profile (TPP). This precision is vital for enhancing bioavailability, particularly for poorly soluble molecules; by increasing the specific surface area, micronization optimizes absorption kinetics, leading to higher peak plasma concentrations (C_max) and improved overall exposure.

For non-oral delivery routes, specifically pulmonary delivery via Dry Powder Inhalers (DPIs), characterization requirements are even more stringent. To ensure efficient deposition in the peripheral airways, particles must be engineered to a precise aerodynamic diameter, typically within the 1–5 μm respirable range. Characterization at this stage must evaluate the interplay between geometric PSD and morphology, as these factors dictate the Fine Particle Fraction (FPF) and the overall efficiency of aerosolization.

Beyond biopharmaceutical performance, precise measurement ensures material homogeneity and allows developers to predict rheological properties, such as powder flow and packing, which are critical for the reliability of high-speed downstream processing and consistent dose uniformity.

Analytical Weighting and Definition Systems

A comprehensive characterization strategy requires an understanding of how different analytical techniques "see" particles. We employ the Moment-Ratio (M-R) definition system to derive mean diameters that possess physical relevance to product properties. It is vital to distinguish between different weighting models:

Number-weighted distributions: Provide equal representation to the fine and coarse fractions; often delivered by microscopy.
Volume-weighted distributions: Where a few large particles can outweigh numerous smaller ones; typical of laser diffraction.

Precise characterization allows developers to predict rheological behaviors, such as poor flow properties or electrostatic charges caused by high surface energy

Customers

Small biotechs to Big Pharma
CDMO’s (API, Dosage Form, Integrated)
Functional Excipient Companies

Phases of Development Supported:

Lifecycle Presence: From Pre-Clinical to Commercial Phase
Fully Equipped from few grams up to metric Ton Batches
One Independent R&D Lab and 3 fully inspected GMP Buildings

Types of Molecules

Small Molecule APIs and HPAPIs
Functional Excipients
NCEs, 505b2s, Generics

Analytical Platforms for Particle Evaluation

To guarantee material homogeneity and confirm the stability of the engineered solid state, we utilize a multi-faceted analytical approach. In the following sections, we will explore the technical specifics of our primary analytical equipment:

Laser Diffraction +

Laser Diffraction (LD) is the industry standard for determining geometric particle size distributions ranging from sub-micron to millimeter scales. Utilizing Low-Angle Laser Light Scattering (LALLS), this technique measures the angular distribution of light intensities as a laser beam passes through a dispersed sample. These scattering patterns are deconvoluted using Mie theory or the Fraunhofer approximation to calculate volume-weighted distributions. LD provides an equivalent spherical diameter, making it highly reproducible for quality control. Its speed and ability to handle both wet and dry dispersions make it indispensable for defining the design space of pharmaceutical processes.

$Laser Diffraction$

Optical Microscopy +

Optical Microscopy is an absolute qualitative technique that provides direct observation of individual drug particles. Unlike indirect analytical methods, it allows for the definitive visual assessment of crystal habit, surface texture, and the quality of dispersion. It serves as a critical tool for identifying unwanted agglomeration or physical modifications.

While manual evaluation is laborious, modern systems utilize graticules or automated stages to improve statistical significance, typically covering a size range from 0.5 μm to 150 μm.

Even considering the above, it remains a vital method for verifying that the physical appearance of the drug substance meets target specifications.

Morphological Characterization +

Imaging techniques utilizes automated static or dynamic systems to provide high-resolution data on individual particle shapes. Because these advanced systems measure particles individually, they generate number-weighted distributions, which provide equal representation to the fine and coarse fractions. These platforms calculate critical parameters such as aspect ratio, sphericity, and circularity, which are essential for predicting a drug's functional performance. By analyzing thousands of particles automatically, imaging bridges the gap between the equivalent spherical diameter and the actual aerodynamic or dissolution behavior of APIs with irregular morphologies.

Laser Diffraction

$Laser Diffraction$

Optical Microscopy

While manual evaluation is laborious, modern systems utilize graticules or automated stages to improve statistical significance, typically covering a size range from 0.5 μm to 150 μm.

Even considering the above, it remains a vital method for verifying that the physical appearance of the drug substance meets target specifications.

Morphological Characterization

Particle Characterization Explained

Particle characterization is how we double-check that medicine pieces have been reduced to the perfect size after processing. This step is vital because the size of these tiny grains directly changes how well the body absorbs the drug and how effective it will be. For treatments like inhalers, particles must be a very specific, tiny size to reach deep into the lungs. Accurate measuring also helps us predict if the powder will clump or move easily through machines. Different tools measure particles in different ways, either by counting each individual piece or measuring the total space they fill

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Particle Characterization

Particle Characterization

The Biopharmaceutical Rationale