Physical Characterization of Excipients

Characterization of excipients is a very important step in the pre-formulation phase of a product, in which testing and analysis of the physical properties of materials can improve the efficiency of manufacturing process. While a series of testing will involve additional time and cost, failure to perform proper characterization testing can result in more costs to the manufacturer. Changes in the physical properties of excipients may further affect the quality of the drug product. In addition, the knowledge gained from raw material characterization can also help to provide better specifications for material procurement. BOC Sciences provides comprehensive expert solutions to deepen your understanding of the key physical properties of excipients.

Figure 1. Physical-Chemical Characterization and Formulation Considerations for Excipients Analysis. (Fu, X.; et al. 2021)

Physical Characterization Techniques

• Laser Diffraction in Dry and Wet Mode: Particle size distribution.
• X-ray Powder Diffraction (XRPD): Identification and quantification of crystalline and non-crystalline (i.e. amorphous) polymorphs. Determination of crystallinity percentage & impurity detection.
• Differential Scanning Calorimetry (DSC): Measure thermal transitions in a broad range of materials including polymers, pharmaceuticals, organic and inorganic materials.
• Thermogravimetry (TGA): Determine rate of chemical degradation at different temperatures.
• Infrared Spectroscopy: Scanning and identification of functional groups within the molecular structure of excipients.
• Scanning Electron Microscopy (SEM): Obtain three-dimensional images of the excipient surface to study catalytic activity and its properties.
• NMR spectroscopy and Mass Spectrometry (MS)

Rheological Characterization

Rheology is the study of the flow and deformation of substances. Polymeric excipients have already become an important addition to complex tablet mixtures, and their processability and functional properties depend on their rheological behavior. Therefore, to fully characterize macromolecular or polymeric excipients and to further understand their variability, our excipient experts comprehensively characterize a range of macromolecular or polymeric excipients including polylactic acid (PLA), polylactic acid (PLGA) and hydroxymethylcellulose and their derivatives, providing average molecular weight, molecular weight distribution and powder flow properties of these excipients.

Assesment of Degree of Substitution (DS)

DS is a value describing the degree of substitution of cellulose derivatives, which is defined as the average number of substituted hydroxyl groups per glucose unit. Currently, products of cellulose ethers or cellulose derivatives are widely used as drug excipients. The DS of cellulose plays a key role in its physicochemical properties such as water solubility, thermal stability, thickening, gelation and film-forming properties. Therefore, accurate determination of DS is the main measure that determines the properties of excipients. BOC Sciences has developed several quantitative measurement methods including nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy(FTIR), elementary analysis (EA), etc., that can be used as computational screening tools in excipient design.

Assesment of Substituent Distribution

The distribution of substituents on the dehydrated glucose units of cellulose is one of the important topics in the design of cellulose-based excipients. The physicochemical properties have been shown to affect the behavior and suitability of tablet excipients. The physical properties of cellulose derivatives are influenced not only by their molecular weight distribution, type of substituent and degree of substitution, but also by the distribution of substituents within the monomeric units and along the molecular backbone. At BOC Sciences, our experts partially hydrolyze the derivatized cellulose chains using specific hydrolytic enzymes, and then analyze the chemical structure of the resulting oligomers in combination with advanced instrumentation and precise analytical methods.

Figure 2. Characterization of different excipients for direct compression. (Mura, P.; et al. 2019)

Assesment of Monomer Ratio

In addition to monomer content and monomer arrangement, the ratio of monomers in the polymer is also critical for the properties of polymeric materials. Polymeric excipients with different monomer ratios exhibit different properties in terms of hygroscopicity, molecular weight (M_w) and glass transition temperature (T_g). Therefore, accurate characterization and tuning of monomer ratios play important role in designing and manufacturing polymeric excipients that perform just right for your drug activity and your patients. We perform a complete chemical hydrolysis of the excipient sample, and after the completion of the hydrolysis process, all individual monomers are separated, identified and quantified to obtain information on the distribution of substituents within the cellulose derivative monomer unit.

Solid-state Characterization

Pharmaceutical products are mostly produced in the form of solid materials, and solid oral drugs remain the most commonly used category of dosage forms. Therefore, physical and chemical characterization of the solid-state properties of excipients is an important part of formulation design and optimization. In general, techniques such as differential scanning calorimetry and thermogravimetric analysis are the most common techniques used for these purposes. BOC Sciences has introduced a series of complementary analytical methods to characterize different types of excipients in solid forms, and to determine physical properties such as particle size, polymorphs and morphology.

Microstructure Analysis

The function of each excipient depends to a large extent on the specific physical properties of the excipient, which are determined by the nature and microstructure of the excipient particles. Therefore, the microstructure of excipients must be accurately and carefully monitored to ensure quality control, safety, and drug stability. BOC Sciences' pharmaceutical microstructure characterization platform supports the analysis of a wide range of pharmaceutical excipient samples.

How BOC Sciences Helps You?

• Experts from the pharmaceutical industry provide advise on data acquisition techniques through infrared, Raman and NMR spectroscopy, including 600 spectra of 300 of the most commonly used excipients.
• Apply useful information from molecular spectra to the physical characterization services.
• Guide formulation design and optimization.
• Calibrated equipment are available to help you characterize a wide range of excipient materials.