Fractal analysis of pharmaceutical particles by atomic force microscopy

Area of Science:

• Materials Science
• Pharmaceutical Technology
• Surface Science

Background:

• Accurate characterization of pharmaceutical solid particle surface roughness is essential for quality control.
• Understanding surface properties aids in correlating roughness with other critical material attributes.

Purpose of the Study:

• To evaluate fractal analysis as a method for describing pharmaceutical particle surface roughness.
• To assess the reliability of the variation method for calculating fractal dimensions from AFM data.

Main Methods:

• Employed atomic force microscopy (AFM) to acquire 3D surface profiles of pharmaceutical particles.
• Utilized the variation method to compute fractal dimensions from the obtained surface profiles.
• Analyzed fractal dimensions of granule, powder, and freeze-dried powder samples.

Main Results:

• Developed and verified a computer program for the variation method using fractional Brownian motion models.
• Most particles and granules exhibited fractal dimensions between 2.1 and 2.2, independent of scan size.
• Freeze-dried samples showed scale-dependent fractal dimensions, increasing up to 2.5 with larger scan sizes.

Conclusions:

• Fractal analysis, particularly with the variation method and AFM, reliably describes pharmaceutical particle surface roughness.
• Fractal dimension estimation requires careful consideration of algorithms, data size, and observation scale (scan size).
• Scale-dependency and multi-fractal features in pharmaceutical materials reflect underlying artificial process controls on surface morphology.