Morphological Analysis of Excipients

Pharmaceutical formulations are complex mixtures of active pharmaceutical ingredients (APIs) and excipients. In order to improve the effectiveness and bioavailability of drugs, pharmacologists have made many efforts to optimize drug formulations. Improvements are required not only chemically but also morphologically, since the physical consistency of the formulation (e.g., homogeneity, texture, particle size, etc.) can affect the bioavailability of the active ingredient. Excipients with suitable particle size, good dispersibility and solid-state properties have good potential to be developed as versatile carrier platforms for potent biomolecules. Knowledge of the morphological characteristics of solid excipients used in pharmaceutical formulations is important to verify the quality of raw materials and to identify variations in the production line. For example, understanding the morphological characteristics of the excipients is important for spray-drying applications, tableting and powder handling or transfers. BOC Sciences’ experienced scientists provide our customers with a variety of imaging techniques that allow them to probe the surface structure of test excipient materials, including optical microscopy, birefringence microscopy, FTIR, and scanning electron microscopy.

Figure 1. The effect of amino acid excipients on morphology and solid-state properties of multi-component spray-dried formulations. (Sou, T.; et al. 2013)

Morphological Characterization Services

At BOC Sciences, a variety of quantitative methods have been established to characterize the morphology of solid excipients. Based on the analysis of individual particles and the quantification of particle shape, we can obtain valuable and more definitive pre-production parameters from the precise imaging. Deviations in the performance of pharmaceutical excipients can be predicted if changes in particle characteristics occur.

Polarized Light Microscopy (PLM)

PLM can distinguish different crystalline polymorphs based on shape, morphology, size and other optical features. Therefore, PLM is the technique of choice for determining whether a sample is crystalline or not. Excipients in solid dosage forms are often crystalline, PLM is a useful characterization technique to evaluate their morphology. Our skilled microscopist have the ability to interpret the sometimes subtle differences in PL images of different crystals. In combination with validated analytical methods, we use optical microscopy to quickly and reliably identify solid excipients.

X-ray Powder Diffractometry (XRPD)

XRD techniques are very useful in analyzing and monitoring the crystal morphology of excipients used in pharmaceutical formulations. The XRD method allows the detection of any changes that may have occurred in the crystalline state of the excipient or the morphology of the filler in the final product. For some polymorphic pharmaceutical excipients, we use XRPD technique for the quantitative analysis of morphology.

Figure 2. Correlating Granule Surface Structure Morphology and Process Conditions. (Orth, M.; et al. 2022)

Scanning Electron Microscopy (SEM)

SEM is well suited for morphological analysis because it provides high-quality nanometer-scale images of powders and particles. At BOC Sciences, SEM can be used to characterize the morphology of cellulose-based excipients such as hydroxypropyl cellulose, and we use the secondary electron imaging assay to examine the morphology of the fibers by SEM. Convolutional neural networks (CNNs) are image analysis techniques that have been applied to image classification in various fields. The classification accuracy of CNN models is high enough to classify excipient types. We have applied CNN to classify SEM images of pharmaceutical excipient powders to detect differences in particle morphology, such as particle size, shape, and surface condition.

Applications

• Batch comparison and evaluation
• Analysis of finished products to help analysts identify the root cause of quality issues
• Visualize the degree of aggregation of excipient particles, providing valuable insight into the quality of raw materials and finished products

Optical Microscopy

Optical microscopy is considered the most accurate because the size and shape of the individual particles can be observed and measured. Based on the optical image of the particle spatial distribution, the excipient particles are automatically identified by the software. Statistical distributions for various morphological parameters, such as size and shape, can be obtained.