Chapter:- Materials of fharmaceutical

Plant Construction
► Covered points
1. General study of composition
2. Factors affecting the selection of material of
pharmaceutical plant
3. Corrosion, corrosion resistance & Properties
4. Corrosion-types, cause, theory of corrosion & its
prevention.
5. Construction with special reference to stainless
steel & glass.
Vishvajitsinh Bhati 3
 Iactors Influencing Ihe �election Of
Materials
• A number of equipment are used in the manufacture of
pharmaceutical, bulk drugs, antibiotics, biological products etc.
• In addition, several accessories such as containers for
processing and packing of finished products are essential.
• A wide variety of material can be utilized for the construction
of equipment.
• In the plant improvement is depend on->(1) Design of
equipment (2) Selection of material (3)Technique of
fabrication.
Vishvajitsinh Bhati 4
• The selection of material for the construction of equipment depends on the
following properties ..
1. Che1nical factors
2. Physical factors Mainly 3 factors are affected
3. Economical factors
• Sub-factors is..
a) Chemical resistance
b) Structure strength
c) Resistance to physical shock
d) Resistance to thermal shock
e) Ease of fabrication
f) Cost
g) Maintenance
Vishvajitsinh Bhati s
 Chemical -
Factors
• The contents should not alter the properties of the material with
which the vessel is made, when these are in contact with each
other, the effects may be understood in two ways:-
1) The consents may react and thus get contaminated with the
material of the plant.
2) The drugs and chemical may destroy the material of the plant.

Vishvajitsinh Bhati 6
Conti..
1)...Product may contaminated by material of equipments and
lead to instability, decomposition and physiological effects, it
may also affect physical properties of products like appearance
and color.
Eg. -presence of traces of heavy metal decompose penicillin
-Stability of vit. Decreased in presence of metallic ions.
-The color of esters will change to pale yellow in presence of
iron impurities.

Vishvajitsinh Bhati 7
2) ...the solutions that come into contact with the equipment are
generally corrosive in nature.
• In addition, equipment are exposed to extremes of pH,
temperature and pressure.
• As a result, the 1naterial gets corroded, losing its strength and
durability. So the life of the equipment is reduced.
• Materials of plants construction assists greatly in providing a
plant that will be resistant to attack of acids, alkalis, oxidizing
agents etc.

Vishvajitsinh Bhati 8
 fhysical !:actors
I. Strength
II. Wear properties
III. Sterilisation
IV. Cleaning
V. Mass
VI. Thermal conductivity
VII. Thermal expansion
VIII.Ease of fabrication
IX. transparency Vishvajitsinh Bhati 9
 §.trength
• In the compression of tablets, the dies and punches
should have sufficient mechanical strength to
transmit the applied pressure, otherwise tablets are
poorly formed.
• Glass satisfies the property of strength, but is
breakable.
• Here, aerosol containers must withstand pressure
as high as 960kPa to 1.20 Mpa at 55° C. Tin plate
containers can satisfy this condition, while plastic
containers can't be used due to its poor mechanical
strength.
Vishvajitsinh Bhati 10
 �ear froperties
• There properties become important, when there is a possibility
of friction between the moving parts.
-Eg. During milling and grinding, the gridding surface wear
off and these materials will be incorporated into powder as
impurities.
-Such type of mills should be avoided, when drugs of high
purity are required.
-The risk of contamination is more due to wear of ceramic or
iron equipment.
Vishvajitsinh Bhati 11
 Sterilisation
• In the production of parenterals products, antibiotics and
biological, sterilisation is an essential step, which is obtained
by autoclaving.
- E.g. Equipment and vessels are made of S.S, because they
can be sterilised easily.

Cleaning
• Smooth and polished surface allow the process of cleaning
easily
- E.g. S.S & Glass are suitabne for this purpose.
Vishvajitsinh Bhati 12
 Mass
• Many times, the equipment should be transported or moved
from one place to another. This is possible when the material is
light in weight, when other factors are satisfactory.

Thermal conductivity
• In industries some time equipment such as evaporators, dryers,
stills and heat exchanger are used, for used good thermal
conductivity materials.
-E.g. iron, glass or graphite tubes are used in the fabrication
of heat exchangers, so that effective heat transfer is possible.
Vishvajitsinh Bhati 13
 Thermal Expansion
• If the material has high coefficient of expansion, the design of
plants may be greatly complicated.
• This increases should be able to maintain size and shape of
equipment at working temperatures.
• The material should be able to maintain size and shape of
equipment at working temperature.

Ease of Fabrication
• During fabrication the material undergoes various process such
as casting, welding, forging, etc..
Vishvajitsinh Bhati 14
 Transparency
• Transparency may be useful property because it
permits the visual observation of the changes
during a process.
• For this resone, borosilicate glass has been use
increasing used in the construction of reactors,
fermentors etc ...

Vishvajitsinh Bhati 15
 Economical Factor
• Cost and 1naintenance of the plant 1nust be economical. The
cost is made up of three parts:-
1. The basic cost of material
2. The fabrication cost
3. The scrap value of the plant at the end of its life.
• It can happen that an apparently expensive material will be
the most economical in long run.
E.g.-: Sub. With better wearing qualities and lower
maintenance cost.
Vishvajitsinh Bhati 16
Classification of Materials for Plant
Const1uction
\laterial of construction
-----

l\letals 'II
-- on-metals
._
 Ferrous Metals
• Iron metal is one of the widely used materials for the
construction of plants because of its mechanical strength,
abundant availability and lower cost.
• So1ne varieties of iron are discussed here,

1. Cast iron
2. Steel carbon
3. Stainless steel

Vishvajitsinh Bhati 18
 Cast Iron
• Consists :Fe+ carbon (1.7+5.0%)+silicone (Si)+ manganese
(Mn)
• Its property is depend on the amount of carbon present in it.
• Cast iron is abundantly available, inexpensive and widely used.
• There is two type of cast iron.

-1) White cast iron

- 2) Grey cast iron

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1) White cast iron: upon fracture it gives a while surface.
• it contains the carbon in the from of the cementite, and is
produced by rapid cooling.
• It is malleable. It is very abrasive and wear resistance. It is
used as liner, for grinding balls, dies and pumps impellers.

2) Grey cast iron: it consist less cementite, its carbon occurs in

the fonn of graphite.
• Grey cast iron is much less hard and brittle than white cast
lfOll.

• Low in cost and easy to cast

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• It has outstanding ability to absorb vibration and wear
resistance.

• Uses:
Supports for plants
Jackets of steam pans
Linings with enamel, plastic or suitable protective material.
14% addition of silicon in cast iron a hard and brittle
casting alloys is formed, which is resistance to attack by
HN0 3 or H 2 S04.

Vishvajitsinh Bhati 21
• Advantage:
-Cheap, it is used in place of expensive plant material with
coatings or linings of enamel or plastic.
-It is resistance to cone. H2SO4 , nitric acid and dil. Alkalis.
-Since cast iron has thermal conductivity, it is used for the
construction of outer surface of jackets of steam pans.
• Disadvantage:
-Cast iron is very hard and brittle.
-Cast iron is attacked by dil. H 2SO4 , dil. nitric acid, and as
well as cone. HCL acid.
-Since cast iron has low thermal conductivity, it can't be used
for heat transfer in stills.,ishvajitsinh Bhati 22
 Carbon Steel or Mild Steel
• Carbon steel is iron alloy, which contains only a small
percentage of carbon.
• Variants of carbon steel:- the property of carbon steel can be
altered by alloying it with other metals and their properties are...
-Nickel (Ni):- improves toughness, corrosion resistance and
low temperature to oxidation.
-Chromium (Cr):- increase hardness, more abrasive resistance
to oxidation.
-Silicon (Si):- increases hardness, more abrasive resistance to
oxidation
- Molybdenum (Mb):- provi'cles 8strength at elevated temp. 23
• Uses:
- Construction of bars, pipes and plates.
- Storage tanks for water, H2 SO4 , HCL and organic solvent, etc..
- Supporting structure such as grinders and bases for plant vessels.

• Advantages:
- Cheapest, therefore it is preferred.
- wieldable and frequently used in fabrication.
• Disadvantages:
- Limited resistance to corrosion
- Its react with caustic soda, brine water and sea-water.

Vishvajitsinh Bhati 24
 Stainless Steel
• There are more than 70 standard types of steel.
• S.S-302 Contains - Fe+ Cr (18%)+ Ni (8%) + C (0.08%)
• S.S-304 Contains - Fe+ Cr (19%)+ Ni (9%) + C (0.08%)
• The abundant use of S.S is due to the properties such as:

- Heat resistance
- Corrosion resistance
- Ease of fabrication
- Cleaning and sterilisation
- Tensile strength
Vishvajitsinh Bhati 25
• Depending on the composition, S.S alloys are
available in three groups, viz., marten sic, ferritic
and austenitic.
Coml!osition Advanta2e Disadvanta2e Uses
Mertensitic : Mildly corrosion Ductility is poor Sink,. bench tops.
Chromium 12-20% resistance, atmospheric storngc tanks, buckets,
Carbon 0.2- 0.4% & organic exposures. mi,mg clements etc..
Nickel up to 2.0%

Ferritic (a- form) Better corrosion Not good against fov.w lining,. baffles,
Chromium: 15-30% resistance, easy to reducing agents . HCL separator. tov. er, heal
Carbon: 0.1% machine, resistant to c,changer, tubings,
Nickel: - oxidation and condensers, fumace
temp.(upto-800°c) parts, pumps shafts,
\ alvc parts.

Austenitic (y-forms) Highly corrosion No1 easy to machine Fem1entors. storage

Chromiwn: 13-20% resistant, readily cleaned, \Cssds. C\aporators.
Nickel: 6-22% sterilizable. ease to weld, e:xtracllon vcsst!ls, small
Carbon: 0.1%<0.25% non-magnetic v, i1.ajit u,l BhJt apparatus. 26
 Type Composition Rcmarks38 Application

Type-I SiO2-80% -Heat resistant -Chemical glass

( Borosilicate Al2O3 - -Chemically inert than soda- ware
Or natural or Pyrex) U.W¾ lime glass -Ovenware
Na2O-7% -High hydrolytic resistance -Container for
K2O-0.5% -Leaching ofNaOH only alkali sensitive
B2O3 - 12% 0.5PPM per yr preparation
CaO-1% -Difficult to melt and mould
-Very costly

Type-2 Treated soda SiO2-75% -High hydrolytic resistance -Containers for

lime glass Al2O3-2% due to surface treatment Alkali sensitive
(soda-glass with Na2 O-0-10% -Softer than borosilicate easy preparations
surface treatment, Ki O-0-0.5% to mould -For food blood,
sulphured containers) B2O3 - 3% -Cheaper than borosilicate plasma and
CaO-10% infusion fluids
-Parental
-Used once only.
■ Type

Type-3
Soda-lime glass
Composition Remarks

SiO2 - 75% -Moderated hydrolytic

Al2O3 -2% resistance
Application

-Medicated bottle
-Only for non-aqueous
ordinary glass Na2O-15% -Easy to mould liquid preparation
Ki0-0- -Yield alkali to water -For powders for
0.5% -Flakes separate out injection
B2O3 - 3% -Loss of brilliance -Not for alkali
CaO-12% -Cheapest sensitive products
-Not for Parental
-Used once only

Type-NP - General purpose - Use for oral and

(Non-Parental) soda-lime glass topical preparation
 Type Composition Remarks Application

Colored glass - In addition of glass - Dose not allow -Used for sunlight
composition metal salts are the U.V rays to sensitive product
added carbon and sulplur pass through. -Do not use for
OR iron and manganese for parenterals unless
Amber color. specified

Lead free glass - As lead -Used for liquid

monoxide is used preparation
in manufacturing -Used when
of glass causes preparation-ment
lead poisoning for lead poisoning
e.g. Na. E.D.T.A.
Silicone treated - Surface is treated with - As hydrophobic
dimethyl siloxane in nature do not
wetted so product
do not cling to
surface
 Glassed Steel
• Glassed steel is an organic product of fusion, which is cooled to a
rigid condition without crystallizing.
• It requires special consideration in its design and use.
• These surface are applied to heavy vessels.
• Normally, several coating are fused in furnace, glassed steel
combines the corrosion resistance of glass with the working
strength of steel.
• Uses:- glass lined steel is used for strong acid, alkalis and saline
solutions. For small-scale manufacture and pilot plant work,
glassed steel vessels are used.
Vishvajitsinh Bhati 41
• Advantages:-
- It has excellent resistance to all acids except hydrofluoric acid and hot
cone. H2 SO4•
- It can be attacked by hot Alkaline solution. Particularly suitable for
piping when transparency is desirable.
- It is brittle and gets damaged by thermal shock. Hence it is protected
using glass lined with epoxy polyester fiber glass.
• Glass lining are resistant to
- All cone. OfHCl acids up to 120 ° C.
- Dil. Cone. OfH2 SO4 up to the boiling point.
- All cone. OfHNO3 up to boiling point.
- Acid resistance glass with improved alkali resistance (up to pH 12).

Vishvajitsinh Bhati 42
 NON METALS - Organic
• Mainly 2 material are widely used in plant construction of this
group...
1. Rubber
2. Plastic
• Other is ...
Wood/Timber
Carbon/Graphite
Silica ware

Vishvajitsinh Bhati 43
 RUBBER
• Rubber is used as such or as lining material for the construction off
plant. Both nature and synthetic rubber are used.
• Types of RUBBER..
I. Natural rubber
II. Soft rubber
III. Hard rubber
IV. Synthetic rubber
a. Neoprene
b. Nitrile rubber
C. Butyl rubber
d. Silicon rubber
e. polyisoprene
Vishvajitsinh Bhati 44
 Ideal Quality of Rubber for Closure
1. Softness and elasticity
2. Impermeable to air and moisture
3. Provide air tight closing
4. Compatible with product
5. Do not migrate any additive to the preparation
6. Negligible extraction of preparation ingredients
7. Withstand sterilization temp.
8. Good ageing qualities
9. Oil resisting for oily preparation
10. Do not yield any fragments.
Vishvajitsinh Bhati 45
 Natural Rubber
:- natural rubber is a naturally occurring polymer, which is
obtain as latex from rubber tree.
- It is common example of an elastomer.
- Elastomer is a substance that can be stretched readily and
when released, rapidly regains its original from.
Soft Rubber
- the naturally occurring polymer is known as soft rubber.
- it is a polymer of monomeric isoprene (C 5 H 8 ).
- its advantage is resistant to dilute mineral acids, dil. Alkali
and salts.
Vishvajitsinh Bhati 46
- It disadvantage is that soft rubber can be attacked by oxidizing
media, oils and organic solvents.
- Uses:- lining materials for plants, as it can bond easily to the
steel.
- After addition of carbon black to the soft rubber gives
hardened rubber. It is used for making tyres, tubes and
conveyor belts.

Hard Rubber
- when soft rubber is 1nixed with sulphur, warmed andl set into a
give!l1 shape, it retains its from. The sulphur combines with the
polymeric chains of rubber and cross-links btwn them. This
process is called vulcanization.
- Soft rubber with 25% or more sulphure is known as hard
rubber. Vishvajitsinh Bhati 47
- Its advantages is hardness and strength.
- Uses:- for making gloves, bands, tubes and stoppers.

Synthetic Rubber
- Synthetic rubber has taken greater importance over natural
rubber due to its superiority in properties such as resistance to
oxidation, solvents, oils and other chemicals.
- Here so1ne type of synthetic rubber are describe in table..

Vishvajitsinh Bhati 48
 Sr. no Synthetic Properties uses
rubber
4. Silicon rubber •Resistant to ..
(Poly-siloxanes) - high and low temp.
- attack to aliphatic
solvents, oils and
greases.

5. Polysoprene •Stable at high

temp., translucent,
flexible.

•Synthetic rubber is thermoplastic, but when mixed with sulphur,

warmed and set into a given shape, it retains its from.
•Vulcanization of 1ubber it possible. It is used for making gloves,
bands and tubes, caps for vials.
Vishvajitsinh Bhati so
• Rubber is soft material, but can be hardened by adding carbon
black.
• Hardened rubber is used for making tubes, tyres and conveyor
belts.

PLASTIC
• Plastic is use in various way, and It is cheap and light in weight
so it is easily transpiration is easy.
• These available in variety of shapes implying that it can be easily
fabricated.
• Plastic material is used for storing a number of substance such as
inorganic salts and weak mineral acids.
Vishvajitsinh Bhati 51
• in machines, plastic material are preferred whenever moving
parts are present indicating that it offers less friction.
• These have better resistance to environmental factors, in similar
manner, plastic materials also used in the construction of plants.
• Plastic are synthetic resins contain long chains of atoms liked to
from giant macromolecules. They have molecular
weight.(103to 107 ).
• Generally Advantages of PLASTIC.
I. Low thermal and electrical res.istance
II. Excellent resistance to weak mineral acids.
III. Unaffected by inorganic salts.
IV. Resistance to slight changes in pH.
Vishvajitsinh Bhati 52
• Plastic have disadvantage like that. ...
I. Low thennal and electrical strength.
II. High expansion rates.
► Basically, two type of plastic are used in pharma. Industry.

1) Thermosetting plastic
Its can be formed under heat and pressure but these can't be
softened or remolded, once hardened.
Some are made from Phenolic and Urea resins.
2) Thermoplastic plastic
Its also 1nade up from heat and pressure but these are
softened and remolded. This is a specific advantage.
Vishvajitsinh Bhati 53
• Some thermoplastic materials and their uses are given below..
- Polyethylene - cables, buckets, pipes
- Polypropylene - milk cartons, ropes
- Polyvinyl chloride - gloves; water proof garments
- Teflon - gaskets, coatings
• Based on the utility of plastic in plant construction, these can be
categorized as:
I. Rigid materials
II. Flexible material
III. Metallic material
IV. Plastic cements
V. Special case plastic
Vishvajitsinh Bhati 54
 Rigid Materials
• These are phenolic resins with various inert fillers. These are
used in the fabrication of a number of items. For e.g. kibosh is a
rigid material and used for gears, bearing etc..It is light in weight.
Some of its application are. . . pumps, ducts, fittings, etc..
• Disadvantage :- these are resistant to corrosion except oxidizing
substance and strong alkalis.

Flexible Materials
• These material is can be rigid or flexible depending upon the
amount of plasticizer added. Used in fabrication..tanks, buckets,
funnels, pipes .. Vishvajitsinh Bhati 55
 Metallic Surfaces
• Plastic of polyethylene or polyvinyl chloride type are used along
with plasticizer for the coating of 1netallic surfaces.
• These are used in the protect the metal from corrosion. And it
applied on tanks, vessels, stirrers, fans.

Plastic Cements
• Used in spaces btwn acid resistance tiles and bricks.

Special Cases
• Used as guards for moving parts of machinery. Nylon and PVC
are use for aseptic screening.
Vishvajitsinh Bhati 56
• we discus types of thermoplastic..
1. Polyolefin's
a) Low density polyethylene [LOP)
b) High density polyethylene [HOP]
c) Poly propylene [PP]
2. Polystyrene
3. Polyvinyl chloride [PVC]
a) Plasticized
b) Unlplastized
4. Polycarbonate
5. Polymethyl - methacrylate [PMMA]
6. Poly amides [NYLONS]
7. Polytetrafluro Ethylene [PTEE]
Vishvajitsinh Bhati 57
 Overall plastics is used as:
• Containers for transfusion solution and retention enemas.
• Containers for Eye and Ear drops, nasal sprays.
• Eye ointment tubes.
• Spray bottles - squeeze bottle.
• Suppositories pack.

• Flexible packing.
• Bottles, jars and closures.

Vishvajitsinh Bhati 58
 Advantages of Plastics
• Unbreakable, tough, flexible, durable.
• Light in weight and easily transported.
• Molded into various shapes and sizes.
• Cheaper.
• Readily and easily 1nanufactured on large scale.
• Pleasant to touch.
• Suck-back feature.
• Odorless.
• Good chemical resistance.
Vishvajitsinh Bhati 59
 Disadvantages of plastics
• Poor conductor of heat - for heat sterilization.
• Attacked by organic solvents and oils.
• Plastic contains - antioxidant, plasticizer and stabilizer - these
substance can be leached to product preparation.
• Chemical binding adsorption of ingredients [Drugs +Additives]
of product with chemicals of plastic so loss of....

- Preservatives
- Antioxidants
- Flavors
.. and hence loss of stability ot.Pv��;11!h�J- 60
• Permeability of moisture and gases CO ,O , known as breathing.
2 2
• Chemical reaction of products ingredients with plastic
ingredients.
• Alternation of physical properties of plastic or products.

Drug-Plastic Consideration
In selecting a plastic container consideration must be given to..
• Composition of material
• Its mechanical and chemical properties.
• Its ease of fabrication and printability.
• Requirement of rigidly or flexibility.
• Acceptance of plastic ingredients by F.D.C.
Vishvajitsinh Bhati 61
Depending on the type of plastic, the total constituents may include
the following..
• Basic polymer • Lubricants
• Residual monomers • Antioxidants
• Plasticizers
• Accelerators
• Slip or antislip additives
• U.V. absorbers
• Modifiers
• Stabilizers
• Filters
Vishvajitsinh Bhati 62