Novel Quality by Design Tools for Concentrated Drug Suspensions: Surface Energy Profiling and the Fractal Concept of Flocculation

Autor: Martin Kuentz, Roberto Bravo, Jiyi Khoo, Jan Kendall De Kruif
Rok vydání: 2013
Předmět:
Zdroj: Journal of Pharmaceutical Sciences. 102:994-1007
ISSN: 0022-3549
DOI: 10.1002/jps.23435
Popis: 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 rheolog- ical 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 lab- oratory 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 in- tensities 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 charac- terized 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. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:994-1007, 2013
Databáze: OpenAIRE
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