Biopharma and Pharma

Analysis of Morphology and Chemical Identification of Pharmaceutical Micro-particles Using Particle Correlated Raman Spectroscopy - Illustration

This study highlights particle correlated Raman spectroscopy (PCRS) as a powerful technique for combining particle characterization with chemical identification, enabling deeper insight into drug performance across various pharmaceutical dosage forms (sprays, tablets, creams).

We introduce EDXRF analysis as a rapid and reliable method for Zinc determination in liquid solution. We demonstrated Zn determination at ppm levels using the calibration curve method with commercial Zinc liquid standard samples. Our calibration curve had a good linearity (R2 > 0.999) and we could accurately determine 22 ppm of Zn in 1 minute. The results demonstrated that EDXRF is an effective tool for rapid and reliable laboratory analysis.

This study demonstrates the potential of A-TEEM™ spectroscopy as a rapid and reliable tool for evaluating lot-to-lot variability in complex cell culture media. By leveraging the distinct spectral fingerprints of aromatic amino acids and vitamins, A-TEEM enables sensitive tracking of compositional differences without the need for extensive sample preparation or lengthy separations.

The Detection of a Low Molecular Weight Enzyme Inhibitor using the OpenPlex system

The use of low molecular weight molecules in the industries of drug discovery and agri-food has become increasingly important over the course of a century of drug research and science development in agriculture and in pharmaceutical field.

This application highlights the development of an oligosaccharide chip (surface functionalization, density of immobilization, spacer arm length) on the same SPRi platform using conductive polymers. These results are highlighted through the example of interactions between HS and SDF-1 α chemokine.

HORIBA provides the pharmaceutical industry, biotech companies and academic research laboratories with high performance instrumentation based on SPRi technology (Surface Plasmon Resonance imaging). To demonstrate the power of this technology, we carried out an experiment based on an antibody-antigen interaction. Original surface chemistry combined with an electrochemical process allows the rapid coupling of biomolecules to the gold layer (polypyrrole co-polymerisation) on the top of a glass prism.

TERS Characterization of phospholipid bilayers and detection of nanoparticles

This application reports on TERS characterization of binary phospholipid bilayer systems deposited onto a gold coated coverslip. Such samples are used as model samples for directly and chemo-selectively visualizing the distribution of a lipid constituent at the nanometer scale.

For the study of a pharmaceutical drug product, particle characteristics (count, size and chemistry) and compound distributions (size and spatial) are among key parameters that strongly determine the quality of the product due to their huge impact on the dissolution rate (and thus bioavailability) for the final solid dosage form. Laser diffraction and Raman microscopy were applied to highlight the benefits of combining two technologies for particle characterization.

We introduced a fast and non-destructive imaging method for inorganic minerals on a multivitamin supplement tablet containing various essential minerals to body functions. We used the HORIBA XGT-9000 X-ray Analytical Microscope for the imaging, and we could visualize the distribution of the key inorganic elements on the tablet less than 20 minutes even though the concentration of the elements are tens of mg or less per tablet.

Quality control of hand sanitizer gels and 70% alcohol products using Raman spectroscopy

Disinfecting your hands with hydroalcoholic gel has become a daily practice. In the meanwhile, 70° alcohol has been used for even longer to disinfect wounds. But, to remain efficient, the alcohol concentration of these products must not be below a defined threshold and must be controlled. This application note demonstrates how to evaluate alcohol concentrations in a quality control process with Raman.

Analysis of microplastics in hand sanitizers using ParticleFinder™ Application Note Picture

Due to the corona crisis, hand sanitizer became part of our daily routine. However, their use is not without potential risks because of their microplastics content. HORIBA offers all the tools necessary to analyze and characterize the presence of Microplastics in hand sanitizers: High-performance Raman microscopes, dedicated filtration kit, and especially the powerful particles detection software ParticleFinder™. We analyzed 3 samples of hand sanitizers, from different countries, and we were able to identify the different plastic content of each.

Raman spectra of DayQuil™ and NyQuil™ collected with an immersion probe fiber-coupled to the MacroRAM™ Raman spectrometer, and a picture of the immersion probe setup.

Raman spectroscopy is well known as a powerful analytical method for qualitative chemical analysis. Less well known is that under certain conditions Raman spectroscopy can also be an effective method for quantitative analysis. Here we demonstrate that capability for quantitative analysis under a variety of conditions, involving different solutes in a solution and solution mixtures, and its applications to pharmaceutical analysis such as content uniformity.

X-ray Fluorescence photons can be partially absorbed by the encapsulated material and will not show in the spectrum. The X-ray transmission image provides a complete picture.

Multiple Characterizations of a Blister Pack Using the XGT-9000

Packaging must provide protection, minimize the loss of constituents and should have no physical or chemical interaction which could alter the quality or present a toxicity risk. With its high degree of versatility, the XGT-9000, HORIBA’s new X-ray microscope, is the perfect tool for the pharmaceutical industry as it can be easily applied within industrial settings, as well as R&D.

Application note - Multimodal Hyperspectral Imaging for Nanotoxicological Applications

An imaging platform that combines Raman microscopy with enhanced darkfield and hyperspectral imaging technology was used to study lung tissue sections containing carbon nanotubes. It enabled easy identification of the regions containing the carbon nanotubes followed by spectroscopic characterization of chemical composition.

We have measured solutions of lysozyme under conditions known to effect its physical state in order to investigate the potential of Raman spectroscopy as a non-invasive and label-free tool to assess protein formulation stability. Results from this study identified specific Raman signature bands in this protein that can be used to identify individual amino acid residues that are reflect structural changes in proteins.

Polymorphisms characterization: when Raman microscopy supports the pharmaceutical industry

Since the physical state can affect the pharmaceutical behavior of drug substances, it is important to know what controls crystallization, solid state reactions, phase stability, and solubility.

Application note: Morphological and chemical characterization of pharmaceutical formulations

One of the major challenges in the pharmaceutical development of a new product consists in its formulation, highly impacting the release and the efficiency of the active molecules in the body.

Raman Hyperspectral Imaging: An essential tool in the pharmaceutical field

Resulting from the combination of Raman spectroscopy and optical microscopy, Raman hyperspectral imaging has proven to be an indispensable tool in the pharmaceutical field. This article will broach a number of Raman hyperspectral imaging applications that were developed in our laboratory, in order to demonstrate the significance of the technique.

In this paper, HORIBA presents evaluation work from CPI showing A-TEEM as a suitable technique to analyze six in-process manufacturing samples of monoclonal antibodies. This work is an initial step toward implementing this technique as a PAT solution in biologics manufacturing.

Accurate monitoring of bioprocesses is essential, as small variations in culture conditions can impact productivity, product quality, and process consistency. One key challenge lies in analyzing the complex, dynamic environment of bioreactors, where media composition, metabolic byproducts, and matrix effects introduce variability. As the industry shifts toward intensified and continuous processing, there's growing demand for rapid, real-time analytical tools that operate under sterile, GMP-compatible conditions. A-TEEM™ technology meets these requirements with its high sensitivity, molecular selectivity, and real-time data output, providing actionable insights for optimizing cell growth and overall bioprocess performance.

Monitoring Cell Culture Media Variability using A-TEEM Spectroscopy

Cell culture media for bioreactors are commonly prepared as aqueous solutions that provide the essential nutrients and conditions required for optimal cell growth, product yield, and quality. Even subtle variations in media composition can significantly impact cell growth rates and yield. Consequently, the identification and analysis of cell culture media are critical for maintaining consistency and optimizing performance.

Kinetic Fluorescence Determination of Vitamin B1

This technical note describes kinetic fluorescence as an analytical technique to quantify non-fluorescent species. The technique is applied to the determination of thiamine (vitamin B1) in solution.

Holistic Analysis of Mammalian Cell Proliferation using Fluorescence Spectroscopy

This study demonstrates the application of Excitation Emission Matrix measurement to monitor cell culture medium conditions during the proliferation of mammalian cells.

Multivariate analysis of different insulin proteins

Stability and aggregation of insulin are studied using simultaneous fluorescence excitation-emission matrices (EEMs) and UV-Vis absorbance spectroscopy. Insulin is a protein-hormone produced by the pancreas and is necessary for basic metabolic processes. Commercial insulin therapeutics generally fall into two categories: short-acting and long-acting insulin. The difference between some short-acting and long-acting insulin lies, in some cases, in only one to three residues in the protein sequence.

Fluorescence Emission spectra of transferrin at increasing concentrations

In this application note, we highlight the high sensitivity of the Duetta for measuring transferrin at very low concentrations. The Duetta spectrofluorometer combines both fluorescence and absorbance measurements simultaneously, thus providing key advantages for protein analysis. In parallel, we compare the fluorescence results obtained using the Duetta with absorbance results obtained with a dedicated low-volume, benchtop spectrophotometer.

Two-dimensional (2D) fluorescence excitation-emission matrix (EEM) spectroscopy has been utilized for over 30 years to characterize or “fingerprint” biological samples. Historically, data acquisition was slow and required extensive corrections. Advances in Charge Coupled Device (CCD) technology and improved data correction methodologies have renewed interest in 2D fluorescence spectroscopy.

Monitoring Biotinylated Adeno-Associated Virus (AAV) using A-TEEM

Adeno-Associated Viruses (AAVs) are becoming widely used as viral vectors to deliver cell and gene therapies and vaccines. As production methods scale to meet growing demand, more information is needed more quickly.

The objective of the measurements is to identify the unknown components and their respective dispersion within pharmaceutical tabs by Raman and FT-IR microspectrometry.

Raman Spectroscopy is a powerful and widely used analytical tool within the pharmaceutical industry. Excipients and active pharmaceutical ingridients (APIs) can be analysed within seconds, and extensive Raman spectral libraries allow easy chemical identification.

Raman Microscopy in Pharmaceutical Salt Analysis

Pharmaceutical and crystallographic samples typically require detailed characterisation and analysis to optimise a samples stability, physical properties and indeed general efficacy where an active drug substance is involved. Furthermore, strict regulatory and manufacturing procedures demand precise characterisation of a solid salt form drug candidate and the possible influence of environmental conditions. The hydration and structure of such samples under varying conditions is important in this full characterisation.

Laser diffraction based particle size analyzers bring the same benefits to nutraceutical measurement that make the technique popular among the pharmaceutical industry: fast analysis time, excellent precision, sample handling systems for every application, and a wide measurement size range. We can readily observe the importance of particle characterization to the nutraceutical industry as this information impacts research and development concerns as well as quality control.

Exosomes are small extracellular vesicles, 30-150 nm in diameter, which have been determined to play a crucial role in extracellular signaling. They have been observed in both prokaryotic and eukaryotic organisms, meaning they are incredibly widely spread in nature. Exosomes bud off from their parent cells in a sealed package, taking the properties of their parent cell walls with them and encasing many intracellular components.

Full and detailed characterization of pharmaceutical formulations is required before release of new drugs. When exposed to warm and humid weather over time, ingredients may undergo change in their hydration level, thus affecting the properties and/or efficiency of the drug. Raman spectroscopy, combined to a temperature and humidity controller can mimic such harsh conditions and can be used to monitor the properties of the different ingre-dients and track their modifications induced by environmental changes.

Resulting from the combination of Raman spectroscopy and optical microscopy, Raman hyperspectral imaging has proven to be an indispensable tool in the pharmaceutical field, especially to study the distribution of active(s) and excipients in a pharmaceutical drug product.

The use of the transmission raman mode instead of the traditional backscattering one brings additional flexibility for the analysis of material, especially when averaged information of bulky samples is required.

Raman Spectroscopy has many useful properties which can be explored and exploited in the analysis of pharmaceutical formulations.

During the last 5-10 years, the molecular solid state has gained recognition by the pharmaceutical industry for its role in drug manufacturing, stability, and activity. In addition, definition of the crystalline phase has become as important as molecular composition in patent protection.

A virus particle consists of several parts including the genetic material (DNA or RNA), a protein coat that protects these genes, and in some cases an envelope of lipids that surrounds the protein coat when they are outside a cell. The size of viruses ranges from a few tens to a few hundreds of nm, which is equal to 1/100 to 1/1000 of the cell (a few to a few tens of μm in size) of any other common living organism.

Raman Investigation of Micro-organisms on a single cell level

Identification of contaminating microbes is an important public safety issue in many fields such as the control of food quality and the manufacture of pharmaceutical and cosmetic products. Previous research has shown the potential for Raman spectroscopy in combination with chemometric methods to investigate bulk samples as well as a single bacterium and yeast cell for classification on the species and strain level.

Traditionally, Raman has been a technique of the material scientist, physicist or chemist, but as instrumentation continues to evolve, the power of Raman in biological and medical applications is fast being realized, not least because of the high information content provided and an excellent tolerance for water.

Successful ophthalmic drug delivery is a combination of pre-corneal retention time, corneal permeability, effectiveness of drug absorption, and dose-to-dose consistency. Whether the drug product is a suspension or microemulsion, it is a complex application involving careful analyses, research, and development efforts.

Process Analytical Technology, or “PAT” is the term given to analytical instruments developed to measure certain attributes of product within the manufacturing process, eliminating, or substantially minimizing the need for sampling for off-line analysis. This approach offers process measurements in-situ with instant access to data, which facilitates rapid decisions during product development and manufacture.

To an outsider to the pharmaceutical industry, the notion of D-values (e.g. D10, D50, D90) being a measure of particle size and distribution is a difficult concept to accept. Basic statistics and a common understanding of distributions might dictate that, provided one is allowed to assume that the particles are relatively spherical, the most logical means of quantifying the particle size of a sample would be to use the mean diameter and standard deviation values.