Process analytical tools for monitoring, understanding, and control of pharmaceutical fluidized bed granulation: A review

Abstract

Fluidized bed granulation is a widely applied wet granulation technique in the pharmaceutical industry to produce solid dosage forms. The process involves the spraying of a binder liquid onto fluidizing powder particles. As a result, the (wetted) particles collide with each other and form larger permanent aggregates (granules). After spraying the required amount of granulation liquid, the wet granules are rapidly dried in the fluid bed granulator. Since the FDA launched its Process Analytical Technology initiative (and even before), a wide range of analytical process sensors has been used for real-time monitoring and control of fluid bed granulation processes. By applying various data analysis techniques to the multitude of data collected from the process analyzers implemented in fluid bed granulators, a deeper understanding of the process has been achieved. This review gives an overview of the process analytical technologies used during fluid bed granulation to monitor and control the process. The fundamentals of the mechanisms contributing to wet granule growth and the characteristics of fluid bed granulation processing are briefly discussed. This is followed by a detailed overview of the in-line applied process analyzers, contributing to improved fluid bed granulation understanding, modeling, control, and endpoint detection. Analysis and modeling tools enabling the extraction of the relevant information from the complex data collected during granulation and the control of the process are highlighted.

Multiobjective Design Method for the Use Processes of Pharmaceutical Excipients Considering Quality and Cost-Effectiveness

“…engineering or pharmaceutical engineering. Process analytical technology (PAT), a group of novel analytical technologies enabling quality control at a higher precision with minimal end testing, such as soft sensors, is one of the most intensively studied fields [4][5][6][7]. Continuous manufacturing of solid drug products is another emerging theme, e.g., [8], which is expected to increase productivity while decreasing batch-to-batch variations in quality.…”

A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

“…∂ ∂t F (n, x, y, t) + ∂ ∂x F (n, x, y, t) dx dt + ∂ ∂y F (n, x, y, t) dy dt = Inf low − Outf low (25) The mass balance of a single component can be simplified according to the equation given below:…”

“…Bardin et al [24] have provided a discussion on the control of PSD during granulation in batch mode, in a high shear mixer. A review on the control of a fluid bed granulation process has been presented by Burggraeve et al [25]. Ramachandran and Chaudhury [26] have suggested a control scheme for a continuous drum granulation process.…”

Applications of Electrical Capacitance Tomography for Research on Phenomena Occurring in the Fluidised Bed Reactors

“…Like EIT, capacitance tomography is mainly used to monitor multiphase processes, such as mixing processes or separation of substances (Tapp et al, 2003). ECT tomography is also used in the petrochemical industry (Ismail et al 2005), drying technology (Rimpilainen et al, 2012;Wang et al, 2009) or pharmaceutical industry (Burggraeve et al, 2013). In the monitoring of multiphase flow, ECT devices may also be applied as flowmeters (Pradeep et al, 2012).…”