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1. What is computational fluid dynamics? Give its pharmaceutical application. – 10m
2. Write about the application of CFD in pharmaceutical industry. – 5m

Computational fluid dynamics: Computational fluid dynamics (CFD) is a simulation tool, which uses
powerful computer and applied mathematics to model fluid flow situations for the prediction of heat, mass
and momentum transfer and optimal design in industrial processes.

• CFD is a versatile tool that is mainly used in complex dynamical process characterisation. Fluid
dynamic studies the effect of force on fuild motion.

• With the evolution of computers a branch of dynamics known as CFD has become a powerful an
cost effective way for simulating real fluid flow.

• CFD is an area of fluid dynamics that is based on Navier–Stokes equation which deals with finding
numerical solutions to equations describing the fluid flow and to obtain a description of the entire
flow field.

• CFD is based on the analysis of fluid flow in a large number of points (elements/volumes) in the
system, which is further connected in a numerical grid/mesh. The system of differential equations
describing the fluid flow is converted, using appropriate methods, to a system of algebraic equations
at discrete points. The obtained system of algebraic equations, which can be linear or nonlinear, is
large and requires the use of computers to be solved.

• Unit operations in the pharmaceutical industry typically handle large amounts of fluid as liquids or
solids. As a result, small increments in efficiency may generate large increments in product cost
savings and hence CFD is an important tool in pharma.

• Examples of CFD applications in development of inhalers, analysis of dissolution apparatus
dynamics and fluidised bed simulations.

Application of CFD in pharmaceutical technology:

• CFD has been recognized as a promising tool for the analysis and optimization of various
pharmaceutical unit operations, process equipment, drug delivery devices, quality control equipment,

• Application of CFD methods in pharmaceutical product and process development may lead to better
process understanding with reduced number of experiments, reduced cost and time savings.

• CFD can be a viable tool for analyzing process equipment. Mixing, separation, drying, fluid
transport, and heat generation operations are some of the processes that can benefit from CFD

• Unlike experimental methods, CFD provides full-field data. Pressure, velocity, density, temperature,
and other parameters of interest can be obtained at each point in the simulated flow domain. Thus
CFD can be implemented in analysis, design, and rapid prototyping at various stages.

• Computational fluid dynamics (CFD) has been widely applied as a trouble-shooting and Quality by
Design (QbD) tool for bioprocess such as fermentation, cell culture, crystallization, emulsification,
and resuspension.


1. CFD for mixing

a. Mixing processes lie at the heart of the pharmaceutical industry, CFD methods can be applied to


examine the performance of mixers and to predict the degree of mixing achieved, thus indicating
whether more mixing elements are required.

b. CFD is a viable method to analyze and optimize stirred tank performance. Impeller performance
and flow-field characteristics can be successfully predicted using CFD.

c. CFD also can be applied to predict shear stress distribution within a stirred vessel. This
evaluation is important for dissolution, emulsification, and dispersion applications. Shear stress
distribution also is important during the processing of biochemical products, when excessive
shear may lead to damage of biocells and loss of product efficacy.

2. CFD for solid handling
a. Nearly 60–80% of pharmaceutical products are in the form of solids. The handling and transport

of solid particles pose several challenges. For example, pneumatic transport of particles is very
common. At times, particles impact the walls of the transport equipment, thus increasing the risk
of erosion.

b. CFD techniques can be applied to analyze such flows and minimize or eliminate the risk of
erosion. CFD also can be applied to analyze the unsteady and chaotic flow behavior in fluidized

3. CFD for energy generation and energy-transfer devices
a. Heat-transfer equipment such as heat exchangers is used throughout a chemical processing plant.

Failure of this type of equipment can lead to downtime and a significant loss of revenue.
b. CFD techniques can be applied to analyze thermal and flow fields within such devices.
c. Through the use and design guidance of CFD simulation, manufacturers can reduce the formation

of pollutants such as NOx.
d. CFD modeling methods also can be applied to gain insight into flame characteristics.

Maintaining flame stability and burner efficiency is very critical to the proper functioning of a
process heater, power plant, or furnace. Flame length, shape, and size can influence the process.

4. CFD for packaging.
a. Liquid pharmaceutical products primarily are supplied in bottles, and decreasing filling time can

shorten time-to-market and increase productivity. To save time, filling equipment can be adapted
to package various products, but splashing, spillover, and frothing are some of the problems
associated with such filling lines.

b. CFD can be applied to conduct virtual experiments before changes are made to the filling lines or
to the package geometry. This method allows a wide range of conditions to be tested and leads to
an optimized filling process

5. CFD in Inhaler development
a. Inhalers have been used for a long time for drug delivery to the lower respiratory tract, in order

to achieve local or systemic effects. These inhalers release a metered quantity of powder in the
airflow, which is drawn through the device by the patient’s inspiration.

b. Besides the optimization of formulation and selection of an appropriate metering system design,
an important factor that determines the performance and efficiency of DPIs (Dry powder
inhalers) is flow path design.

c. DPI performance seems to be most dependent on the airflow through the device, such as on the
patient’s inspiration, in order to achieve sufficient turbulence to fluidize the powder bed.



d. Different mouthpiece designs, cylindrical, conical, and oval, were analyzed using CFD. They

found pronounced influence of mouthpiece geometry on flow field in the mouthpiece, which
affected the velocity of the exiting airflow.

e. Further CFD was used to design various grids for different aperture sizes and was analyzed to
evaluate the influence of impaction against a grid structure at different flow rates (60, 100, or 140
L/min) on agglomerate break-u p and aerosolization efficiency.

f. They investigated the influence of device design, size, and morphology of carrier particles on
performance of the carrier- based DPI system. Carrier particle trajectories were modeled with
CFD and the results were compared with those obtained by in vitro drug deposition studies.

6. Dissolution apparatus hydrodynamics
a. Dissolution testing is widely used in the pharmaceutical industry for optimization of formulation,

testing of batch- to-batch reproducibility, stability testing, obtaining marketing approval for new
and generic drugs, testing how the post- approval changes made to formulation or manufacturing
procedure affect drug product performance, development of an in vitro- in vivo correlation.

b. CFD can be successfully applied for simulation, analysis, and gaining insight into the
hydrodynamic conditions present in different dissolution apparatus.

c. CFD is partly attributed to the complex hydrodynamics, which are not well understood and seem
to be variable at different locations within the vessel. It was shown that small differences in tablet
position within the vessel can affect the hydrodynamics, leading to pronounced differences in
dissolution rates

d. Application of CFD provided an insight into the three-dimensional mixing route throughout the
paddle apparatus, which has not been possible to achieve with velocimetry measurements.

e. CFD was used to simulate fluid flow within the basket dissolution apparatus at different stirring
speeds. Results obtained by CFD simulations were compared with results from flow visualization
techniques and with published ultrasound- pulse-echo velocity data. It was shown that CFD can
give good predictions of fluid flow within basket apparatus.

7. Fluidized bed process simulation:

a. Fluid bed processors are used in the pharmaceutical industry for various unit operations, such as
mixing, drying, granulation, and coating.

b. Process optimization usually requires laborious and extensive experimental work and thorough
process understanding, which is the main obstacle for the wider use of fluid bed processors in the
pharmaceutical industry.

c. Application of numerical modeling techniques, such as CFD, might improve process
understanding and reduce the experimental work.

d. One of the most important factors affecting the efficiency of the fluid bed process is the air flow
and its distribution within the processing chamber.

e. CFD is used to investigate the effects of the air distributor design and the upstream air supply
system on the airflow in a top- spray fluid bed processor. CFD simulations were verified by
experimental methods, using air mass flow rate, pressure drop, and inner wall temperature

f. Theoretical analysis coupled with CFD simulations to predict granule–granule and droplet–
granule collision rates of fluidized bed melt granulation. CFD simulations provided interesting
information about hydrodynamics in the region around the spray nozzle.



g. It was concluded that analysis of droplet spreading and solidification, may improve

understanding of the events occurring during granulation and may be useful for qualitative and
quantitative prediction of aggregation rates.