Microstructure Analysis of Excipients

Due to the diversification of the routes of administration of active ingredients, formulations design involves the application of different physical carriers. According to different formulation types, polymer excipients have different functions in the formulation, such as matrix forming agents, binders or sustained release agents. The functionality of each excipient is largely determined by its physical properties, which are determined by the its microstructure. Properties such as viscosity, solubility and API status have a great impact on the efficacy of the drug, and these key properties are largely influenced by the microstructure of the substances in the formulation. Insights into the microstructure of excipient materials can help improve the bioavailability and stability of product. Therefore, a correct formulation requires accurate characterization of the microstructure of excipients, which can be used to optimize formulation design and ensure drug quality and potency.

Figure 1. Microstructural characterization of carrier-based dry powder inhalation excipients. (Mustafa, M. A. 2019)

Key performance of microstructure attributes for an excipient sample include but are not limited to:

• Microporosity
• Particle size distribution
• Homogeneity and connectivity of excipients

Why is Microstructure Analysis Important?

• Assist in understanding the link between excipient microstructure and final product performance, thereby avoiding unnecessary manufacturing costs
• Accelerate critical process design and decisions with high-resolution insights on microscale phenomena
• Provide long-term insights across the entire formulation design

Characterization of Microstructure of Excipients

X-ray Microscopy (XRM)

Recently, XRM has been successfully applied as a direct and rapid method for tracking the properties of excipient particles as well as microstructure for the control of final solid dosage forms.

• Our experts are able to apply artificial intelligence (AI)-assisted XRM image analysis tools to quantitatively analyze a wide range of excipient particles, such as microcrystalline cellulose (MCC). We offer the size distribution of MCC particles through the obtained XRM characterization images.
• For some novel excipients which enhance the bioavailability of drug particles by having a high porosity, thus providing rapid liquid uptake and disintegration to accelerate subsequent drug dissolution, BOC Sciences has introduced advanced X-ray computed microtomography for their characterization, providing information on the shape and orientation of the pores within the powders.

Figure 2. X-ray Microscopy for Assessment of API and Excipient Microstructure. (Zhu, A., et al. 2022)

X-ray Scattering (XRS)

XRS has proven to be a powerful tool for characterizing materials containing nanoscale layered structures. BOC Sciences provides small- and wide-angle X-ray scattering (SWAXS) for rapid structural analysis of nano-sized structure of excipient materials.

• We offer characteristic fingerprints of excipients by determining the crystallinity at the atomic level.
• For topically applied pharmaceutical creams containing up to 20 excipients, we analyze the molecular structure of creams using SWAXS and molecular dynamics simulations to determine the structural sites and arrangements of excipients.

Gel Permeation Chromatography (GPC) - Infrared Spectroscopy (FTIR)

At BOC Sciences, our formulation team uses a combination of gel permeation chromatography and infrared spectroscopy to characterize the structural properties of excipients. We can help customers use the GPC-FTIR method to complete the development of excipients for a series of novel pharmaceutical carriers:

• Structural information over the entire molecular weight (MW) distribution.
• Monitor potential degradation during scale-up and manufacturing process.
• QA/QC departments use GPC-FTIR as a control tool for routine monitoring of drug formulations, and to monitor the consistency of excipients by examining compositional variations over the MW distribution.

Raman Spectroscopy

Raman imaging, with its superior chemical specificity and less influence by the physical properties of the sample, is used to obtain 3D structural information of the tablets. Our experts use Raman technology to obtain the general distribution of the entire tablet, which is used to extract structural information by combining the image analysis with statistical methods. For example, the size distribution of individual components can be characterized.