Fractal and Polarization Properties of Light Scattering Using Microcrystalline Pharmaceutical Aggregates

Fractal and polarization analysis of diffusively scattered light is applied to determine the complex relationship between fractal dimension of structural morphology and concentration of chemically active ingredients in two pharmaceutical mixture systems including a series of binary mixtures of acetaminophen in lactose and three multicomponent blends with a proprietary active ingredient. A robust approach is proposed to identify and filter out multiple- and single-scattering components of scattering indicatrix. The fractal dimension extracted from scattering field reveals complex structural details of the sample, showing strong dependence on low-dose drug concentration in the blend. Low-angle diffraction shows optical halo patterns near the angle of specular reflection caused by light refraction in microcrystalline aggregates. Angular measurements of diffuse reflection demonstrate noticeable dependence of Brewster's angle on drug concentration. It is shown that the acetaminophen microcrystals produce scattered light depolarization due to their optical birefringence. The light scattering measurement protocol developed for diffusively scattered light by microcrystalline pharmaceutical compositions provides a novel approach for the pattern recognition, analysis and classification of materials with a low concentration of active chemical ingredients.

Automated summary

Fractal and polarization analysis of diffusively scattered light were applied to determine the complex relationship between the fractal dimension of structural morphology and concentration of chemically active ingredients in pharmaceutical mixtures. A robust approach was proposed to identify and filter out multiple- and single-scattering components of scattering indicatrix, revealing complex structural details of the sample. The study shows a novel approach for pattern recognition, analysis, and classification of materials with low concentration of active chemical ingredients using light scattering measurement protocol.