A PAT Approach to Enhance Process Understanding of Fluid Bed Granulation Using In-line Particle Size Characterization and Multivariate Analysis

Abstract

The purpose of this study was to achieve improved process understanding of fluid bed granulation using in-line particle size analyzer in conjunction with multivariate methods. The combined use of process analyzers and multivariate tools provides a useful means to drug development within the framework of quality by design utilizing process analytical technology. The evaluation of in-line monitoring manufacturability quality attributes, particle size, and particle size distribution, was conducted using the Parsum probe which is based on spatial filtering technique. Several granulation batches were manufactured and monitored using a commercial-scale fluid bed granulator. Reference measurements by offline Malvern MasterSizer showed good agreement with those by Parsum at end-of-spray phase. Multivariate/batch statistical process control methods were used to evaluate batch process performance, batch-to-batch variation and develop potential control strategy. The results indicated that the Parsum analyzer is a viable tool for in-line particle size characterization and improved process understanding in combination with multivariate tools.

In-line spatial filtering velocimetry for particle size and film thickness determination in fluidized-bed pellet coating processes

“…Plitzko and Dietrich focussed on the in-line SFV detection of pellet agglomeration during Wurster coating [30], while SFV has recently been established for in-line particle size monitoring in fluidized bed granulation [27,[31][32][33][34][35][36]. The obtained SFV data improved the understanding of the impact of process variables by using model-based process control approaches, such as DoE, univariate and multivariate PLS.…”

Monitoring and control of coating and granulation processes in fluidized beds – A review

“…Huang et al [58] applied the SFV technique to monitor the growing of particles in-line in a fluidized bed, utilizing a multivariable analysis to verify the performance, process variations and study the possibility of implementation of process control. The evolution of chord length (volume based) and particles circulation rate, were determined by the Malvern Parsum SFV probe IPP 70-S.…”

“…Comparisons performed with sieving were concordant Burggraeve et al [57] 2010 SFV Used the SFV technique for the understanding and monitoring of the granulation process. Comparisons with off-line techniques showed good prevision of data Huang et al [58] 2010 SFV Monitored the growing of particles during the granulation and used multivariable analysis to evaluate the performance of the process Dieter et al [59] 2011 SFV Particle size was monitored in granulation and coating processes. The end-point in the granulation and undesirable agglomeration in the coating process could be detected feed-back controller (PID) using moisture content as the controlled variable and the atomizing liquid flow rate as the manipulated variable.…”

In-line particle size measurement and agglomeration detection of pellet fluidized bed coating by Spatial Filter Velocimetry

“…The application of the relatively new method of Spatial Filter Velocimetry (SFV) for the measuring of rate and chord length of the particles in fluidized bed granulation is already under investigation [9][10][11][12][13][14] but the use in fluidized bed coating is in the early stage [15,16]. In general the application of the SFV method in fluidized bed apparatus in laboratory, pilot and production scale is possible.…”