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STUDIES ON GRANULATION, DRYING AND TRIBOCHARGING BEHAVIOUR OF PHARMACEUTICAL POWDERS IN A FLUIDIZED BED DRYER

Date

2021-06-23

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Type

Thesis

Degree Level

Doctoral

Abstract

Wet granulation and drying are two crucial unit operations in the pharmaceutical industry. The two operations can be conducted in one piece of equipment, namely a fluidized bed. Fluidized beds have the advantages of excellent mixing, large contact area, and superior heat and mass transfer. Drying is typically operated at bubbling and turbulent regions. Despite the wide applications of fluidized beds in wet granulation and drying, there still remain challenges. Observation and measuring the dynamic granulation process are challenging with conventional experimental methods due to the opaque nature of pharmaceutical powders and the complex interaction between powders and liquid taking place in a short period of time. In this study, the dynamic granulation process was, for the first time, captured with synchrotron-based X-ray imaging techniques. The dynamic interaction between the pharmaceutical powders and the liquid binder was captured by high-resolution X-ray images. Results show that pharmaceutical powder properties, including particle size, hydrophilicity, and morphology, have significant influences on the dynamic granulation process and the final granular product. After wet granulation, the presence of high moisture content within pharmaceutical granules results in considerable cohesiveness. Agglomeration, channeling, defluidization, caused by the strong inter-particle forces, pose significant challenges to fluidization and drying, particularly at the beginning of the drying process. In this work, the drying performance of pharmaceutical granules was investigated in a pulsation-assisted fluidized bed dryer. It was found that pulsed airflow is effective in eliminating channeling and enhancing the drying rate at higher superficial gas velocity. Lower pulsation frequency is more favoured to improve the drying rate. Two typical drying stages were observed during the drying process, the constant rate period and the falling rate period. During the constant rate period, energy efficiency is between 60% to 45% for the drying process. The energy efficiency falls to 10% during the falling rate period. Nine thin-layer drying models were examined to predict the drying curve of the pharmaceutical granules. It was found that the Midilli and Kucuk model provided the best agreement between the experimental results and the predicted values. The pharmaceutical granules can be easily charged because of repeated collision and separation between particles and between particles and wall. The tribocharging behaviour of the pharmaceutical granules in a conventional FBD and a PFBD was investigated by varying operating conditions such as superficial gas velocity, inlet air temperature, pulsation frequency, and pulsed air ratio. It was found that the specific charge of the pharmaceutical granules remained lower than 0.2 µC/kg during the constant rate period. When the moisture content was reduced to a critical moisture content, namely 10%, the specific charge increased sharply regardless of the superficial gas velocity and inlet air temperature. Then, the increase in the specific charge continued before it reached an equilibrium value during the falling rate period. The equilibrium specific charge is influenced by the superficial gas velocity and pulsation frequency. Higher superficial gas velocity and lower pulsed frequency resulted in a higher specific charge. When the superficial gas velocity is low, there is no noticeable difference between the conventional FBD and the PFBD at different pulsation frequencies. The inlet air temperature and pulsed air ratio did not show an impact on the equilibrium specific charge value.

Description

Keywords

Wet granulation, Synchrotron X-ray imaging, Pharmaceutical powders, Fluidized bed, Drying, Electrostatic, Charging, Tribocharging.

Citation

Degree

Doctor of Philosophy (Ph.D.)

Department

Chemical and Biological Engineering

Program

Chemical Engineering

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