title: Introducing diffusing wave spectroscopy as a process analytical tool for pharmaceutical emulsion manufacturing.
abstract: Emulsions are widely used for pharmaceutical, food, and cosmetic applications. To guarantee that their critical quality attributes meet specifications, it is desirable to monitor the emulsion manufacturing process. However, finding of a suitable process analyzer has so far remained challenging. This article introduces diffusing wave spectroscopy (DWS) as an at-line technique to follow the manufacturing process of a model oil-in-water pharmaceutical emulsion containing xanthan gum. The DWS results were complemented with mechanical rheology, microscopy analysis, and stability tests. DWS is an advanced light scattering technique that assesses the microrheology and in general provides information on the dynamics and statics of dispersions. The obtained microrheology results showed good agreement with those obtained with bulk rheology. Although no notable changes in the rheological behavior of the model emulsions were observed during homogenization, the intensity correlation function provided qualitative information on the evolution of the emulsion dynamics. These data together with static measurements of the transport mean free path (l*) correlated very well with the changes in droplet size distribution occurring during the emulsion homogenization. This study shows that DWS is a promising process analytical technology tool for development and manufacturing of pharmaceutical emulsions.
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, Institute of Pharma Technology, Muttenz CH-4132 Switzerland; LS Instruments, Fribourg CH-1700, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Reufer
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, Institute of Pharma Technology, Muttenz CH-4132 Switzerland.
authors.forename: Alexandra H E
authors.initials: AHE
authors.lastname: Machado
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, Institute of Pharma Technology, Muttenz CH-4132 Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Niederquell
authors.affiliation: Galderma Spirig, Spirig Pharma AG, Egerkingen CH-4622, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Bohnenblust
authors.affiliation: Galderma Spirig, Spirig Pharma AG, Egerkingen CH-4622, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.affiliation: LS Instruments, Fribourg CH-1700, Switzerland.
authors.forename: Andreas Charles
authors.initials: AC
authors.lastname: Völker
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, Institute of Pharma Technology, Muttenz CH-4132 Switzerland. Electronic address: martin.kuentz@fhnw.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D004058:Diffusion; D004655:Emulsions / Q000737:chemistry*; D010316:Particle Size; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D012212:Rheology; D013057:Spectrum Analysis / Q000379:methods*; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; D011135:Polysaccharides, Bacterial; D014867:Water; C002563:xanthan gum
keywords: diffusing wave spectroscopy (DWS); emulsions; gel; light scattering; manufacturing; microrheology; physical characterization; polymer; process analytical technology (PAT)