Legge, E J; Stewart, M; Contreras Chevez, L P; Zhang, H; Tsikritsis, D; Belsey, N A; McAllister, M; Murphy, J R; Mingard, K; Minelli, C (2024) Advanced chemical and imaging methods for studying structure morphology and excipients solid state transformations in pharmaceutical multiparticulate formulations. Journal of Pharmaceutical Sciences, 113. pp. 2464-2474.

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Abstract

The formulation of paediatric medicines faces significant challenges to meet the requirements for safe and accurate administration to children, 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 the advanced methods of (1) environmentally-controlled SEM to monitor temperature- and humidity-induced changes in-situ, and (2) a variety of Raman spectroscopies including stimulated Raman scattering microscopy to identify and localise the different ingredients at the surface and inside the multiparticulate formulations.

These techniques allowed the unprecedented monitoring of specific changes to the particulate structure and distribution of individual formulation ingredients due to product aging. These techniques should be considered as valuable novel tools for in-depth characterisation of multiparticulate formulations to further understand the chemical changes occurring during their development, manufacturing and long-term storage. We envisage these techniques to be useful in furthering the development of a range of future medicine formulations.

Item Type:	Article
Keywords:	Multiparticulates; Physicochemical properties; Stability; Imaging methods; Formulation; Poloxamer 407; Glyceryl Dibehenate; Stimulated Raman scattering microscopy; Environmental scanning electron microscopy
Subjects:	Biotechnology > Biopharmaceutical Manufacturing and Characterisation
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1016/j.xphs.2024.05.004
Last Modified:	18 Oct 2024 10:59
URI:	https://eprintspublications.npl.co.uk/id/eprint/10073