title: Novel quality by design tools for concentrated drug suspensions: surface energy profiling and the fractal concept of flocculation.
abstract: Quality by design is an important concept, but only limited research has been invested in concentrated pharmaceutical suspensions. A need exists for novel analytical tools to thoroughly characterize the drug as well as its aggregated particle structure in suspension. This work focuses on lipid-based pharmaceutical suspensions for filling of capsules. A rheological approach, namely the fractal concept of flocculation, is introduced to the pharmaceutical field. The model drug mebeverine hydrochloride was first physicochemically analyzed. A special aim was to study the surface energy profiles using inverse gas chromatography as a critical characteristic for the suspension's rheological behavior. Suspensions were manufactured in laboratory process equipment while applying different homogenization speeds. Flow curves of the final suspensions were measured using a cone-and-plate rheometer. As a result, surface energy profiles revealed differences from one mebeverine lot to another. Different homogenization intensities greatly affected the viscosity and the Mooney model was able to predict experimental values as a function of the drug volume fraction. The fractal concept of flocculation characterized mebeverine in suspension and a slight increase of fractal dimension was noted when homogenization speed was increased. It was concluded that the introduced concepts have large potential for designing quality into concentrated pharmaceutical suspensions.
authors.affiliation: Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
authors.forename: Jan Kendall
authors.initials: JK
authors.lastname: de Kruif
authors.forename: Jiyi
authors.initials: J
authors.lastname: Khoo
authors.forename: Roberto
authors.initials: R
authors.lastname: Bravo
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D002214:Capsules; D005427:Flocculation; D017709:Fractals; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D010276:Parasympatholytics / Q000737:chemistry*; D010316:Particle Size; D010627:Phenethylamines / Q000737:chemistry*; D012212:Rheology; D013499:Surface Properties; D013535:Suspensions; D014783:Viscosity
chemical_list: D002214:Capsules; D008055:Lipids; D010276:Parasympatholytics; D010627:Phenethylamines; D013535:Suspensions; C005096:mebeverine