title: Fuzzy Logic-based expert system for evaluating cake quality of freeze-dried formulations.
abstract: Freeze-drying of peptide and protein-based pharmaceuticals is an increasingly important field of research. The diverse nature of these compounds, limited understanding of excipient functionality, and difficult-to-analyze quality attributes together with the increasing importance of the biosimilarity concept complicate the development phase of safe and cost-effective drug products. To streamline the development phase and to make high-throughput formulation screening possible, efficient solutions for analyzing critical quality attributes such as cake quality with minimal material consumption are needed. The aim of this study was to develop a fuzzy logic system based on image analysis (IA) for analyzing cake quality. Freeze-dried samples with different visual quality attributes were prepared in well plates. Imaging solutions together with image analytical routines were developed for extracting critical visual features such as the degree of cake collapse, glassiness, and color uniformity. On the basis of the IA outputs, a fuzzy logic system for analysis of these freeze-dried cakes was constructed. After this development phase, the system was tested with a new screening well plate. The developed fuzzy logic-based system was found to give comparable quality scores with visual evaluation, making high-throughput classification of cake quality possible.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
authors.forename: Hjalte
authors.initials: H
authors.lastname: Trnka
authors.forename: Jian X
authors.initials: JX
authors.lastname: Wu
authors.forename: Marco
authors.initials: M
authors.lastname: Van De Weert
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
mesh_terms: D005103:Expert Systems; D005612:Freeze Drying / Q000379:methods*; D017143:Fuzzy Logic; D007091:Image Processing, Computer-Assisted / Q000379:methods; D044367:Phase Transition
keywords: cake quality; expert system; freeze-drying; fuzzy logic; high throughput technologies; mathematical models; image analysis; protein formulation