Introduction
Within the pharmaceutical industry there has been a drive in recent years for better product understanding through increased product knowledge. Towards this end, the ability to measure the particle size of the active pharmaceutical ingredient(s) (API) in product blends and formulations has provided valuable insights into product efficacy, which has the potential for translation into cost savings. The particle size distribution (PSD) is a particularly important characteristic in the development and manufacture of oral and nasal inhaled drug products (ONIDPs), as it is the main determinant of whether the API particles will reach their intended destination and function as required. The most common method for performing this analysis uses manual microscopy and visual identification of the API particles within a blend dispersion. These analyses can be time consuming, subjective and inaccurate. This application note describes how the combination of automated image analysis with Raman spectroscopy in the Morphologi G3-ID can be applied to increase both the accuracy and robustness of these types of measurements by chemically identifying and isolating the particles of interest within a dry powder inhaler (DPI) formulation.
Method
A commercially available DPI sample comprised of two APIs was dry dispersed using the Morphologi G3's integrated sample dispersion unit (SDU) at high pressure onto an aluminum coated microscope slide. The particle size and shape were measured by automated image analysis, according to a standard operating procedure. For this analysis, the size range of interest was between 1 and 10 μm. All particles in that size range were grouped together in a "class", and subsequently targeted for Raman spectral analysis to determine their chemical identity. A spectral reference library was created by taking Raman point spectra of the pure components. The library and particle spectra were preprocessed to minimize baseline variation and normalized to minimize differences in peak intensities. The chemical identity of a particle is then determined by correlating its spectrum against the library spectra. The more similar a particle spectrum is to a library component, the closer its correlation score is to 1. The particles were classified based on their designated chemical identity and the particle size distribution (PSD) determined on the resulting population. >> Download the full Application Note as PDFMalvern Instruments provides the materials and biophysical characterization technology and expertise that enable scientists and engineers to understand and control the properties of dispersed systems. These systems range from proteins and polymers in solution, particle and nanoparticle suspensions and emulsions, through to sprays and aerosols, industrial bulk powders and high concentration slurries. Used at all stages of research, development and manufacturing, Malvern’s materials characterization instruments provide critical information that helps accelerate research and product development, enhance and maintain product quality and optimize process efficiency. Our products reflect Malvern’s drive to exploit the latest technological innovations and our commitment to maximizing the potential of established techniques. They are used by both industry and academia, in sectors ranging from pharmaceuticals and biopharmaceuticals to bulk chemicals, cement, plastics and polymers, energy and the environment. Malvern systems are used to measure particle size, particle shape, zeta potential, protein charge, molecular weight, mass, size and conformation, rheological properties and for chemical identification, advancing the understanding of dispersed systems across many different industries and applications. Headquartered in Malvern, UK, Malvern Instruments has subsidiary organizations in all major European markets, North America, Mexico, China, Japan and Korea, a joint venture in India, a global distributor network and applications laboratories around the world. www.malvern.com severine.michel@malvern.com
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