Rebecca Power is studying chemical and biopharmaceutical engineering in Cork Institute of Technology. She undertook her industrial placement in a pharmaceutical company. This article describes the final-year research project she subsequently completed for the client pharmaceutical company. [caption id="attachment_35810" align="alignright" width="300"]pic1 Fig 1: Film coating pan and tablet cores (Ima Pharma, 2017)[/caption] The formulation of excipients and active pharmaceutical ingredients (API) into tablets involves a number of operations. The final operation is the film coating of tablet cores. Tablet cores are loaded into a pan, which rotates, and film-coating suspension is then sprayed onto the tablet cores through guns (as shown in Fig 1). The film-coating suspension is prepared and pumped through the film-coating machine. The main focus of this project was the optimisation of the suspension mixing for a product in the client pharmaceutical company. In the film-coating unit operation in the client pharmaceutical company, an aqueous pigmented suspension is prepared in a 150L mixing vessel using pigmented powder and purified water and sprayed onto tablet cores. As part of a cycle-time reduction project, it is desired to scale up the vessel size and quantity of suspension prepared to reduce preparation and cleaning time for the product. The aim of this project was to optimise the mixing of the suspension in the larger scale 300L vessel, following on from issues with unsuspended solids during industrial trials, with the areas of study shown below. [caption id="attachment_35811" align="aligncenter" width="300"]pic2 CLICK TO ENLARGE Fig 2. Project outline and areas of study[/caption] With regard to carrying out a material properties analysis, a number of different properties of the suspension and pigmented powder were determined experimentally, with the apparatus used and the average values obtained shown below. These values were used in subsequent calculations and modelling.

Property Apparatus Used Average Result
Suspension viscosity Brookfield Rheometer 0.0436 Pa.s
Suspension zeta potential Malvern Zetasizer -14.45mV
Suspension density Graduated cylinder 1113.7kg/m3
Pigmented powder particle size Scanning Electron Microscope 30μm
Table 1: Material properties analysis results
 

Mixing apparatus/methodology

[caption id="attachment_35812" align="alignright" width="209"]film-coating suspension Fig 3: Lab mixing vessel set-up[/caption] To experimentally study the mixing of the film-coating suspension, the industrial 300L mixing vessel was scaled down to a laboratory scale using a constant tank diameter to impeller diameter ratio, yielding the laboratory set-up as shown below. The suspension preparation steps were as follows: powder addition, five-minute high speed mix to incorporate the powder, one hour of deaeration to remove entrapped air from the suspension and recirculation to simulate mixing during use in the film-coating unit operation. The parameters shown below relate to the mixing vessel set-up and suspension preparation which were studied through mixing modelling and mixing trials to determine the optimum set-up parameters to leave no unsuspended solids.  
Impeller height Suspension fill level Impeller speed
Powder addition rate Number of impellers Position of agitator shaft
Table 2: Parameters studied to determine optimum vessel configuration
[caption id="attachment_35820" align="alignright" width="260"]pic4 Fig 4. Dynochem representation of laboratory vessel[/caption] With regard to the modelling of mixing, the just suspension speed (Njs) is the impeller speed at which the solid particles are just suspended (Zwietering, 1958). The following calculations and modelling were completed:
  • Both the Zwietering correlation and gas-material balance (GMB) correlation were used to calculate Njs for different laboratory vessel configurations.
  • These configurations were also modelled in Dynochem software, which calculated Njs based on the Zwietering correlation. The Dynochem representation of the laboratory vessel is shown in Fig 4.
  • The Bittorff and Kresta correlation determined the impeller speed needed to achieve a uniform suspension with the results for each vessel configuration below.
Distance between impellers (cm) Shaft Location Impeller Speed for Uniform Suspension (rpm)
1.8 Central 252
0 Central 230
1.8 Side-mounted 297
0 Side-mounted 271
Table 3: Impeller speed results for different lab vessel configurations

Experimental mixing trials

[caption id="attachment_35823" align="alignright" width="300"]film-coating suspension Fig 5: Unsuspended solids at bottom of laboratory vessel with side-mounted shaft[/caption] Experimental trials were completed using different impeller and shaft configurations in the chosen laboratory vessel. The impeller speeds calculated during mixing modelling were used for the one hour deaeration step. The amount of unsuspended solids post mixing was measured in each case as shown below with the initial main results also shown below. A side-mounted impeller shaft (position 1), as is present in the industrial vessel, gave a high amount of unsuspended solids with very little observed for a centrally located shaft (position 2). A configuration with two impellers, with one placed higher along the shaft, is also more favourable. Further experimentation with this impeller configuration and a side-mounted impeller shaft was completed. Doubling the mass of suspension prepared in the vessel with this configuration was the optimum case, with no unsuspended solids observed.

Conclusions and recommendations

  • [caption id="attachment_35825" align="alignright" width="300"]pic6 CLICK TO ENLARGE Fig 6; Graph of mean of means of unsuspended solids versus parameter levels[/caption] The zeta potential results prove that the suspension is unstable, therefore unsuspending of solids can occur at any stage during the mixing process due to insufficient mixing.
  • During mixing modelling, it was determined that the GMB correlation gave a large overestimation of Njs so the Zwietering correlation is more applicable for this mixing system.
  • From the mixing experimentation, it was determined that a centrally located impeller shaft produces less unsuspended solids.
  • Experimental results showed that the impeller speed must be increased during in use mixing to prevent the unsuspending of solids.
  • The optimum case for the off-centrally located shaft was scaled up to industrial scale. The scaling up results are shown below.
 Parameter 300L Mixing Vessel
Powder addition impeller speed (rpm) 361
Five minute, high-speed mix impeller speed (rpm) 399
One hour deaeration impeller speed (rpm) 120
In-use mixing impeller speed (rpm) >120
Table 4: Results for 300L mixing vessel
Acknowledgements Many thanks to my industrial supervisor and my academic supervisor in Cork Institute of Technology, Dr Caroline O’Sullivan. References Zwietering T.N., 1958, Chemical Engineering Science, Vol. 8, pp. 244-253, 1958. Ima Pharma, 2017, Coating pan - GS HT-HE-HP, [online]. Available at: http://www.ima-pharma.com/Product/EN/Products-F575/Solid_Dose_Processing_%2F_Manufacturing-S591/Coating-T619/Solid_wall_pans-Q622/Coating_pan___GS_HT_HE_HP-M39.html [Accessed on: 18/04/17]

Engineers Journal competition for best student article of 2017

The competition is for the best article by an undergraduate chemical or bioprocess engineering student published in the Engineers Journal during 2017. The first prize is €300, with two further runners-up prizes of €100 each. The aim of the award is to encourage chemical and bio-process engineering students to publish articles in the Engineers Journal, thereby publicising the work of undergraduate students. The competition, which is being run in association with the Chemical and Process Engineering Division of Engineers Ireland, is open to all undergraduate chemical-engineering students studying in Ireland (including those who graduate during the year of the competition). Both content and presentation will be considered when judging articles. The editor of the Engineers Journal may choose a judging panel. The decision of the editor of the Engineers Journal will be final. Chemical-engineering students who wish to enter the competition should send their articles (and any accompanying images) to Mary Anne Carrigan at mcarrigan@engineersireland.ie.