title: Study of an ultrasound-based process analytical tool for homogenization of nanoparticulate pharmaceutical vehicles.
abstract: There are currently no adequate process analyzers for nanoparticulate viscosity enhancers. This article aims to evaluate ultrasonic resonator technology as a monitoring tool for homogenization of nanoparticulate gels. Aqueous dispersions of colloidal microcrystalline cellulose (MCC) and a mixture of clay particles with xanthan gum were compared with colloidal silicon dioxide in oil. The processing was conducted using a laboratory-scale homogenizing vessel. The study investigated first the homogenization kinetics of the different systems to focus then on process factors in the case of colloidal MCC. Moreover, rheological properties were analyzed offline to assess the structure of the resulting gels. Results showed the suitability of ultrasound velocimetry to monitor the homogenization process. The obtained data were fitted using a novel heuristic model. It was possible to identify characteristic homogenization times for each formulation. The subsequent study of the process factors demonstrated that ultrasonic process analysis was equally sensitive as offline rheological measurements in detecting subtle manufacturing changes. It can be concluded that the ultrasonic method was able to successfully assess homogenization of nanoparticulate viscosity enhancers. This novel technique can become a vital tool for development and production of pharmaceutical suspensions in the future.
authors.affiliation: Institute of Pharma Technology, University of Applied Sciences Northwestern Switzerland, CH-4132 Muttenz, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Cavegn
authors.affiliation: Krieger Ltd., CH-4132 Muttenz, Switzerland.
authors.forename: Ryan
authors.initials: R
authors.lastname: Douglas
authors.affiliation: Krieger Ltd., CH-4132 Muttenz, Switzerland.
authors.forename: Guy
authors.initials: G
authors.lastname: Akkermans
authors.affiliation: Institute of Pharma Technology, University of Applied Sciences Northwestern Switzerland, CH-4132 Muttenz, Switzerland. Electronic address: martin.kuentz@fhnw.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D000077215:Clay; D005782:Gels; D007700:Kinetics; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D011786:Quality Control; D012822:Silicon Dioxide / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D014463:Ultrasonography; D014783:Viscosity
chemical_list: D000538:Aluminum Silicates; D005782:Gels; D014677:Pharmaceutical Vehicles; D011135:Polysaccharides, Bacterial; D012822:Silicon Dioxide; D002482:Cellulose; C109691:microcrystalline cellulose; D000077215:Clay; C002563:xanthan gum