Identifying overarching excipient properties towards an in-depth understanding of process and product performance for continuous twin-screw wet granulation

Abstract

The overall objective of this work is to understand how excipient characteristics influence the process and product performance for a continuous twin screw wet granulation process. The knowledge gained through this study is intended to be used for a Quality by Design (QbD)-based formulation design approach and formulation optimization. A total of 9 preferred fillers and 9 preferred binders were selected for this study. The selected fillers and binders were extensively characterized regarding their physico-chemical and solid state properties using 21 material characterization techniques. Subsequently, principal component analysis (PCA) was performed on the data sets of filler and binder characteristics in order to reduce the variety of single characteristics to a limited number of overarching properties. Four principal components (PC) explained 98.4% of the overall variability in the fillers data set, while three principal components explained 93.4% of the overall variability in the data set of binders. Both PCA models allowed in-depth evaluation of similarities and differences in the excipient properties.

A multivariate approach to predict the volumetric and gravimetric feeding behavior of a low feed rate feeder based on raw material properties

“…In a next step, the material properties can be linked via multivariate models with the process behavior at different unit operations of a continuous manufacturing line (e.g., feeders, blenders) (Clayton, 2015). Research has already been successfully conducted using this approach for granulation and tableting processes (Fonteyne et al, 2014;Garcia-Munoz, 2014;Haware et al, 2009aHaware et al, , 2009bThoorens et al, 2015;Van Snick et al, 2018b;Willecke et al, 2017). Once a predictive platform is developed for a unit operation, the characterization of a small amount of powder is sufficient to predict the behavior of that material at the specific unit operation.…”

A novel approach to support formulation design on twin screw wet granulation technology: Understanding the impact of overarching excipient properties on drug product quality attributes

“…Avicel PH101 vs. Avicel PH301). The 8 selected fillers were extensively characterized as described in a previous paper [12]. Using PCA, the overarching properties of the filler data set were identified.…”

“…5 factors were studied in the experimental design. 3 factors were the score values of the 3 principal components (PC) derived from the PCA of the fillers data set which consisted of the fillers' physicochemical and solid state properties [12]. These 3 PCs together defined the filler type in the formulation where PC1 represented the moisture-related, PC2 the flow-related and PC3 the density/particle sizerelated filler properties.…”

“…Therefore, one of the main challenges was to investigate a broad range of excipient properties which might potentially impact the drug product's pCQAs as factors in the same DoE study. As previously described by the authors in [12], principle component analysis (PCA) was used to reduce large data sets of excipient characteristics (1 data set for fillers and 1 data set for binders) to a limited number of overarching properties (i.e. the principal components).…”

“…Figure 1 depicts the step-wise systematic approach that was followed in this study [13]. The performance and results of steps 1-4 were published in [12], while steps 5-8 are presented in this publication. First, pharmaceutical fillers and binders suitable for twin screw wet granulation were selected and extensively characterized with regard to their physico-chemical properties and solid state characteristics (steps 1 & 2).…”