1. Advanced Chemical and Imaging Methods for Studying Structure Morphology and Excipients Solid State Transformations in Pharmaceutical Multiparticulate Formulations.
- Author
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Legge, Elizabeth J., Stewart, Mark, Contreras Chávez, Lourdes P., Zhang, Hannah, Tsikritsis, Dimitrios, Belsey, Natalie A., McAllister, Mark, Murphy, John Richard, Mingard, Ken, and Minelli, Caterina
- Subjects
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RAMAN microscopy , *RAMAN scattering , *LASER microscopy , *RAMAN spectroscopy , *SCANNING electron microscopy - Abstract
The formulation of paediatric medicines faces significant challenges to meet the requirements for safe and accurate administration, while maintaining a suitable taste. Multiparticulate formulations have a strong potential to address these challenges because they combine dose flexibility with ease of administration. Understanding the stability of multiparticulate formulations over storage as a function of time and environmental parameters, such as humidity and temperature, is important to manage their commercialisation and use. In this work, we have expanded the toolkit of available techniques for studying multiparticulates beyond those such as scanning electron microscopy (SEM) and confocal laser scanning microscopy. We include advanced methods of environmentally-controlled SEM to monitor temperature- and humidity-induced changes in-situ , and a variety of Raman spectroscopies including stimulated Raman scattering microscopy to identify and localise the different ingredients at the surface and inside the multiparticulates. These techniques allowed unprecedented monitoring of specific changes to the particulate structure and distribution of individual ingredients due to product aging. These methods should be considered as valuable novel tools for in-depth characterisation of multiparticulate formulations to further understand chemical changes occurring during their development, manufacturing and long-term storage. We envisage these techniques to be useful in furthering the development of future medicine formulations. [Display omitted] • Raman spectroscopy mapping of the surface of multiparticulates, with corresponding scanning electron microscopy (SEM) imaging to combine chemical and physical information. • Accelerated aging studies within environmental SEM (ESEM), combined with Raman spectroscopy point measurements to identify chemical and structural changes. • Stimulated Raman scattering (SRS) microscopy imaging to rapidly identify the location of the API and excipients across large particle populations. • Insights into the behaviour of poloxamer 407 and glyceryl dibehenate in multiparticulates when exposed to different environmental conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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