CITRIC ACID PRODUCTION

The upstream part of the production process does not do anything with the material itself,
such as processing the material. The upstream stage of the production process involves
searching for and extracting raw materials. This part of the process simply finds and extracts
the raw material. For citric acid production, the upstream process involves starch hydrolysis
with α- amylase which resulted dextrin formation. Also at upstream step, mineral nutrients
and nitrogen sources prepared and sterilized.

The downstream stage in the production process involves processing the materials collected
during the upstream stage into a finished product. For citric acid production, the downstream
process starts after fermentation. This stage involves biomass separation, which held by rotary
filter and ultrafiltration.After filtration, the dilute solution of citric acid is passed through
columns of activated charcoal and ion exchangers so as to remove colours and other
impurities. Purified crystals of citric acid are obtained after evaporation of water. In order to
evaporate water, the solution goes to crystallization. After this step, the mother liquid is
separated from suspension with rotary vacuum filter. Separated crystals transfer to the
fluidized bed dryer to dry with air. [1]

Fig 1.Process flow diagram of citric acid downstream process

Downstream Process Design

1. Fermenter
The process divided into 3 steps, which are dextrin conversion to glucose, fungal
biomass growth with glucose and citric acid transformation from glucose.
Equipment Design Parameters:
 Fermenter operability and reliability
 Temperature and pH controls
 Productivity and yield
 Product purification
 Water management
 Energy requirements
 Waste treatment

Assumptions:

 Since it is a batch fermenter;no inflow or out flow FAO = FA = 0

𝑉 𝑑𝑁𝐴
General mole balance equation FAO - FA + ∫0 𝑟𝐴 ∗ 𝑑𝑉 = 𝑑𝑡

𝑑𝑁𝐴 𝑉
For a single batch reaction, the component balance can be written as = ∫0 𝑟𝐴 ∗ 𝑉
𝑑𝑡

 The fermenter is of constant volume V = V0

𝑑(𝑁𝐴 ⁄𝑉0 ) 𝑑𝐶𝐴
Therefore; the equation = 𝑟𝐴 can be written as = 𝑟𝐴
𝑑𝑡 𝑑𝑡

 The fermenter is perfectly mixed

𝑉 𝑉 𝑑𝑁𝐴
Thus; ∫0 𝑟𝐴 ∗ 𝑑𝑉 = 𝑟𝐴 ∫0 𝑑𝑉 = 𝑟𝐴 ∗ 𝑉 and = 𝑟𝐴 ∗ 𝑉
𝑑𝑡

 The mass of biomass produced per unit mass of substrate (YXS) is constant
during the fermentation time
𝑔𝑟𝑜𝑤𝑡ℎ 𝑟𝑎𝑡𝑒 − ΔX − ΔX − ΔX
YXS = 𝑠𝑢𝑏𝑠𝑡𝑟𝑎𝑡𝑒 𝑐𝑜𝑛𝑠𝑢𝑚𝑝𝑡𝑖𝑜𝑛 𝑟𝑎𝑡𝑒 = = that equation is written as YXS =
Δ𝑆𝑇 Δ𝑆𝐺 + ΔS𝑅 Δ𝑆𝐺

 A very concentrated feed is being provided to the fermenter and the

change in volume is negligible [2]
2. Rotary Vacuum Filter

Biomass removal is the first step of downstream processing of citric acid production.
This step can be accomplished by using one (or more) of the following
unit operations: rotary vacuum filtration, disk-stack or decanter centrifugation, press
filtration, microfiltration, ultrafiltration, flotation, etc. This unit consists of a rotary
drum which is partially immersed in a fermentation broth. Rotating drum adsorbs
cellular bio-mass. Once the biomass is out of fermentation broth, it is partially dried
and then removed from the drum. Rotary vacuum filters can operate continuously
for long periods of time. The most important disadvantage of this type of unit is the
problem with the disposal of the mixture of filter-aid and biomass. Filter-aid is added
in equal or higher amounts than biomass. Stringent environmental laws have made it
costly to dispose of such solid materials. Therefore, if the disposal cost of filter aid is
relatively high where a new plant is going to be built, alternative unit operations
should be considered for biomass separation. However, if the disposal cost of
filter aid is relatively low, a rotary vacuum filter is a good choice.[3]

3. Ultrafiltration
Equipment Design Parameters:

 Installation
 Flush
 Integrity test
 Equilibration
 Processing (feed composition, feed flow, concentration at end points)
 Recovery
 Sanitization (sanitant type, T, concentration, time, feed flow)
 Storage

The molecular weight cut-off of the membrane is selected to retain the product while
allowing undesirable impurities (mainly low molecular weight solutes) to pass through
the membrane. The low operating temperature and the purification achieved along
with concentration are some of the advantages of ultrafiltration over evaporation.

 Utilizes a membrane to separate particles that are much larger than the solvent
used
 Successful removal occurs in the particle size range of 10 solvent molecular
diameters to 0.5 µ [3]
 4. Ion – Exchange Chromatography

Based on the adsorption of ions onto ion exchange resin.

Equipment Design Parameters:

 Flow conditions
 Mass transfer from the fluid phase to the surface of the stationary phase
 Diffusion inside the pores of the stationary phase
 Size of the stationary phase particles.

Assumptions

 The chromatographic process is isothermal;

 Negligible axial dispersion flow for the liquid phase
 The mobile phase velocity remains constant during a run;
 The compressibility of the mobile phase is negligible;
 The packing material is made of porous particles that are spherical and
uniform in size;
 The adsorbent bed is homogeneous;
 The concentration gradient in the radial direction of the adsorbent bed is
negligible
 The liquid phase inside the pores is assumed to be stationary and is not
affected by the movement of the mobile phase;

With the assumption of instantaneous equilibrium, isothermal conditions and negligible axial
dispersion, the mass balance for the fluid phase for a column with constant flow through it
can be described by the following partial differential equation
𝜕𝑐 𝜕𝑐 (1 − 𝜀𝑡𝑜𝑡𝑎𝑙) 𝜕𝑞
𝑢 + + =0
𝜕𝑧 𝜕𝑡 𝜀𝑡𝑜𝑡𝑎𝑙 𝜕𝑡

𝜀𝑡𝑜𝑡𝑎𝑙describes the overall void fraction of the bed and q the loading per volume of adsorbent
material given by the corresponding isotherm. The velocity of the mass transfer zone v(c) can
then be calculated.[4]
𝑢
𝑣(𝑐) = (1 − 𝜀𝑡𝑜𝑡𝑎𝑙) ∆q
1+
𝜀𝑡𝑜𝑡𝑎𝑙 ∆c
 5. Adsorption Chromatography (De-colorization)

Adsorption chromatography is based on the interaction between the solute molecules and
active sites on the stationary phase. This interaction depends on the polarity of solutes.
This technique proves the statement that “polar like polar”. Because if the stationary phase
is more polar than the mobile phase then high polar compounds in the mixture will tightly
bound to the stationary phase where less polar compounds will lightly bound to the
stationary phase. Less tightly bound compounds will be eluted out by the mobile phase
earlier than the tightly bonded ones. Design is held, based on the principles of general
adsorption.
[𝐴𝑔 ]
𝐾𝑒𝑞 = [𝐴𝑔 ]∗[𝑆]

Equipment Design Parameters:

 Nature of adsorbate and adsorbent.

 The surface area of adsorbent.
 Activation of adsorbent.
 Experimental conditions. (temperature, pressure, etc.)

Assumptions:

 Complete reversibility
 No change in solution properties/ state due to interactions
 One to one binding between chemical and adsorption side (only within site
specific binding)
 One mode of binding only described by a single Keq
 [S] ≫ [𝑨𝒈 ]

Therefore, equation becomes, [𝐴𝑔 ] = 𝐾𝑒𝑞 ∗ [𝐴𝑔 ]

Concentration of adsorbed species can be expressed as a multiple of the concentration of

dissolved species.

6. Crystallization

Equipment Design Parameters:

 Purity
 Physical form (particle size)
 Chemical properties (structure, solubility, molecular weight etc.)
 Stability
 Experimental conditions (temperature, pressure, etc.)
 Starting conditions
 Assumptions

 size-independent growth
 no crystal agglomeration or breakage
 nucleation rate equal to the sum of the primary and secondary nucleation
rates
 perfectly mixed crystallizer with crystals homogeneously distributed
andno crystal accumulation on the bottom of the crystallizer

7. Fluidized Bed Dryer

Equipment Design Parameters:

 Temperature
 Humidity
 Air flow rate
 Initial moisture content
 Batch size

Assumptions

- For heat transfer simplification

 The temperature change of the bed with time is essentially a first-order
response.
 Wall effects are neglected.
 There is thorough intermixing of the solids.
 The model does not account for a difference in aggregative or particulate
fluidization.
 The bed particles are in thermal equilibrium with the surrounding fluid.
 The bed temperature is constant with time
 The exit gas temperature is equal to the temperature of the exiting particles.
The solids are discharged at the upper limit of the expanded bed.
 The gas inlet temperature is constant and the initial bed temperature is
referenced to zero.
- For mass transfer simplification
 The diffusion rate within the particle is not high.
 The materials are nonreactive.
 The concentration of particles within the gas is constant throughout the bed.
 The change in concentration with time in the exit solid is a first-order response.
 The moisture content of the exit stream is the same as the majority of the bed
with the exit stream at the top of the bed.
 The moisture content of the incoming solids is constant with time.
Critical Quality Attributes and Critical Process Parameters

The term critical quality attribute (QCA) iscommonly used in process analytical
technology and quality by design forthose properties that are critical defining the
quality of the manufactured product (Physical, chemical, biological, or
microbiological
property or characteristic that should be within an appropriate limit, range, or
distribution to ensure the desired product quality). The QCA needs to be monitored
and controlled inappropriate ways.Process parameter criticality is linked to the defined
acceptable rangefor the process parameter.

The pH of fermentation medium is known as one of the most critical parameter

for citric acid production processes by yeasts. It is reported that initial pH of the
fermentation medium must be very well defined and optimized depending on the
microorganism, substrate and production technique. When working with yeasts, initial
pH values above 5 should be used since citric acid production is adversely affected
below pH 5. [5]Citric acid accumulation is strongly influenced by the type and
concentration of carbon source. The type of the carbonsource can be varied
according to the microorganism used. Substrate profiles of A. niger and yeasts used
for citric acid
production can be extremely different from each other. For A. niger, sucrose is the
most favorable substrate among theeasily metabolized pure carbohydrates, followed
by glucose, fructose and galactose. [6]
 References

1) Biwer P., Heinzle E. Early Ecological Evaluation in Biotechnology through Process

Simulation: Case Study Citric Acid. Eng. Life Science,2002;2: 265–268

2) Perlman D. Annual Reports on Fermentation, Academic Press, 2014, 63-64

3) Harrison R. G.,Todd P., Petrides D. P. Bioseparations Science and Engineering Oxford

University Press. 2015;2:469

4) Schmidt H. Preparative Chromatography: of Fine Chemicals and Pharmaceutical

AgentsWiley-VCH Verlag, 2015, 217

5) Mattey M. The production of organic acids. Critical Reviews in Biotechnology.

1992;12(1/2):87-132

6) Yalcin S.K. Citric acid production by yeasts: Fermentation conditions,

processoptimization and strain improvement. Current Research, Technology and
Education Topics in Applied Microbiology A. Mendez – Vilas, 2011