Material of Construction
Syllabus:
General study of composition, corrosion, resistance.
Properties and applications of the materials of construction with special
reference to stainless steel and glass.
A number of equipment are used in the manufacture of
pharmaceuticals, bulk drugs, antibiotics, biological products etc. A wide
variety of materials are used.
Classification of
material of construction:
 |
FACTORS INFLUENCING THE SELECTION OF MATERIALS OF
CONSTRUCTION
The selection of a material for the construction of
equipment depends on the following properties:
1. Chemical
factors
(i)
Contamination of the product
(ii)
Corrosion of material of construction
2. Physical
factors
(i)
Strength
(ii)
Mass
(iii)
Wear properties
(iv)
Thermal conductivity
(v)
Thermal expansion
|
(vi)
Ease of fabrication
(vii)
Cleaning
(viii)
Sterilization
(ix)
Transparency
|
3. Economic
factors
1. Chemical factors
Whenever a chemical substance is placed in a container or
equipment the chemical is exposed to the material of construction of the
container or equipment. Therefore, the material of construction may contaminate
the product (contamination) or the
product may destroy the material of construction (corrosion).
Contamination of product:
Iron contamination may change the
color of the products (like gelatin capsule shells), catalyze some reactions
that may enhance the rate of decomposition of the product.
Leeching of glass may make aqueous
product alkaline. This alkaline medium may catalyze the decomposition of the
product.
Heavy metals such as lead, inactivate penicillin.
Corrosion of material
of construction:
The products may be corrosive in
nature. They may react with the material of construction and may destroy it.
The life of the equipment is reduced.
Extreme pH, strong acids, strong
alkalis, powerful oxidizing agents, tannins etc. reacts with the materials,
hence some alloys having special chemical resistance are used.
2. Physical factors
Strength
The material should have sufficient
physical strength to withstand the required pressure and stresses.
Iron and steel can satisfy these properties. Tablet punching
machine, die, upper and lower punch sets are made of stainless steel to
withstand the very high pressure.
Glass, though has strength but are brittle.
Aerosol container must withstand
very high pressure, so tin plate
container coated with some polymers (lacquered) are used.
Plastic materials are weak so they are used in some packaging
materials, like blister packs.
Mass
For transportation
light weight packaging materials are used. Plastic, aluminium and paper
packaging materials are used for packing pharmaceutical products.
Wear
properties
When there is a
possibility of friction between two surfaces the softer surface wears off and
these materials contaminate the products. For example during milling and
grinding the grinding surfaces may wear off and contaminate the powder. When
pharmaceutical products of very high purity is required ceramic and iron
grinding surfaces are not used.
Thermal
conductivity
In evaporators,
dryers, stills and heat exchangers the materials employed have very good
thermal conductivity. In this case iron, copper or graphite tubes are used for
effective heat transfer.
Thermal
expansion
If the material has
very high thermal expansion coefficient then as temperature increases the shape
of the equipment changes. This produces uneven stresses and may cause
fractures. So such materials should be used those are able to maintain the
shape and dimension of the equipment at the working temperature.
Ease
of fabrication
During fabrication
of an equipment, the materials undergo various processes such as casting,
welding, forging and mechanization etc. For example glass and plastic may be
easily moulded in to containers of different shape and sizes. Glass can be used
as lining material for reaction vessels.
Cleaning
Smooth and polished
surfaces makes cleaning easy. After an operation is complete, the equipment is
cleaned thoroughly so the previous product cannot contaminate the next product.
Glass and stainless steel surfaces can be smooth and polished, hence are easy
to clean.
Sterilization
In the production of parenteral,
ophthalmic and bulk drug products all the equipment are required to be
sterilized. This is generally done by introducing steam under high pressure.
The materials must withstand this high temperature (1210C) and
pressure (15 pounds per square inch). If rubber materials are there it should
be vulcanized to withstand the high temperature.
Transparency
In reactors and fermentors a visual
port is provided to observe the progress of the process going on inside the
chamber. In this case borosilicate glass is often used.
In parenteral and ophthalmic
containers the particles, if any, are observed from with polarized light. The
walls of the containers must be transparent to see through it. Here also glass
is the preferred material.
3.
Economic factors
Initial cost of the equipment depends
on the material used. Several materials may be suitable for construction from
physical and chemical point of view, but from all the materials only the
cheapest material is chosen for construction of the equipment.
Materials those require lower
maintenance cost are used because in long run it is economical.
CORROSION
Definition: Corrosion
is defined as the reaction of a metallic material with its environment, which
causes a measurable change to the material and can result in a functional
failure of the metallic component or of a complete system.
Classification of corrosion according to the environment
1. Dry corrosion: It involves the direct
attack of gases and vapor on the metals through chemical reactions. As a result
an oxide layer is formed over the surface.
2. Wet
corrosion: This corrosion involves purely electrochemical reaction, that
occurs when the metal is exposed to an aqueous solution of acid and alkali.
e.g. Zn + 2HCl
®
ZnCl2 + H2
THEORY OF CORROSION
1. Corrosion reaction
on single metal
A single piece of metal (e.g. Fe) when comes in contact with
acid (e.g. HCl ) small galvanic cells may be set up on the surface.
Each galvanic cell consists of (i) anode regions and (ii)
cathode regions.
Reaction at anode:
Fe on the iron leaves two electrons to the metal and itself becomes Fe++
ion. Fe++ ion is soluble in water, so it is released in the medium.
Thus the iron surface is corroded.
Reaction at cathode:
The released electron is conducted through the metal piece into cathode region.
Two electrons are supplied to two protons (H+ ) to form two atoms of H. Hydrogen atoms are
unstable, hence two H atoms will combine to form a molecule of stable H2.
In the absence of acid , water itself dissociates to generate H+
ion.
2H+ + 2e– ® H2 Hydrogen (H2) forms bubbles
on the metal surface. If the rate of hydrogen formation is very slow then a
film of H2 bubbles will be formed that will slow down the cathode
reaction, hence the rate of corrosion will slow down. If the rate of hydrogen
production is very high then hydrogen molecules cannot form the film on the
surface. So the corrosion proceeds rapidly.
2. Corrosion
reactions between metals
If two metals come in contact with a common aqueous medium
then one metal will form anode and the other will form cathode. Now if both the
metals are connected with a wire the reaction will proceed. Anode metal will be
corroded and hydrogen will form at the cathode.
For example if a zinc and a copper plate is immersed in an
acidic medium then zinc will form anode and will be corroded while hydrogen
will be formed at copper plate.
Abode reaction: Zn ® Zn++ + 2e–.
Cathode reaction: 2H+ + 2e– ® H2
So anode will be corroded and hydrogen will be evolved at
cathode.
3. Corrosion
involving oxygen
The oxygen dissolved in the electrolyte can react with
accumulated hydrogen to form water. Depletion (reduction) of hydrogen layer
allows corrosion to proceed.
At cathode: O2
+ 2H2 ® 2H2O
The above reaction takes place in acid medium. When the
medium is alkaline or neutral oxygen is absorbed. The presence of moisture
promotes corrosion.
FACTORS INFLUENCING CORROSION
1. pH of the solution
·
Iron dissolves rapidly in acidic pH.
·
Aluminium and zinc dissolves both in acidic and
alkaline pH.
·
Noble metals are not affected by pH e.g. gold
and platinum.
2. Oxidizing agents
Oxidizing agents may accelerate the corrosion of one class
of materials whereas retard another class.
·
e.g. O2 reacts with H2 to
form water. H2 is removed, corrosion is accelerated. Cu in NaCl
solution follows this mechanism.
·
e.g. Oxidizing agents forms a surface oxide
(like Aluminium oxide) and makes the surface more resistant to chemical attack.
4. Velocity
When corrosive medium moves at a high velocity along the
metallic surface, the rate of corrosion increases due to:
·
Corrosion products are formed rapidly and washed
away rapidly to expose new surface for corrosion reaction.
·
Accumulation of insoluble films on the surface
is prevented.
·
The corrosion is rapid in the bends in the
pipes, propellers, agitators and pumps.
5. Surface films
·
Thin oxide films are formed on the surface of
stainless (rusting). These films absorbs moisture and increases the rate of
corrosion.
·
Zinc oxide forms porous films. Fluid medium can
enter inside and thus corrosion continues. Nonporous films of chromium oxide or
iron oxide prevent corrosion.
·
Grease films protect the surface from direct
contact with corrosive substances.
TYPE OF CORROSION
1. Fluid corrosion:
General
When corrosion is generally confined to a metal surface as a
whole, it is known as general corrosion. This corrosion occurs uniformly over
the entire exposed surface area. E.g.
Swelling, cracking, softening of plastic materials.
2. Fluid corrosion:
Localised
(a) 
Inter-granular
corrosion: During heat treatment or welding, some components get
precipitated at the grain boundary of the metal. These boundaries acts as
anodes and grains as cathodes. So
corrosion of anode region occurs.
Inter-granular
corrosion: During heat treatment or welding, some components get
precipitated at the grain boundary of the metal. These boundaries acts as
anodes and grains as cathodes. So
corrosion of anode region occurs.
(b) Pitting
corrosion: On metal surface small holes or pits are created due to local
corrosion and these pits increase in size rapidly. In the pits the metals
dissolves rapidly especially by chlorine and chloride ions.
(c) Stress
corrosion: Certain area of metal may be subjected to thermal, mechanical or
chemical stresses. The surface area becomes anode and acts as corrosion area.
(d) Fretting
corrosion: Equipment showing high vibrations destroys the surface of metal
(e.g. steels balls in ball-bearing) by mechanical hitting.
(e) Corrosion
fatigue: Cyclic stress breaks the protective film, so corrosion increases.
3. Fluid corrosion: Biological
Metabolic action of micro-organisms can either directly or
indirectly cause deterioration of a metal by:
(i) Creating
electrolyte concentration cells on the metal surface.
(ii) Influence
the rate of anodic / cathodic reactions.
(iii) Sulphates are
reduced by reducing bacteria and produces hydrogen peroxide (H2S)
that reacts with iron to produce ferrous sulphide (FeS). Thus the iron gets
corroded.
PREVENTION OF CORROSION
Following methods may be adopted for
preventing or reducing corrosion:
1. Material selection
(a) Pure
materials have less tendency towards pitting, but they are expensive and soft.
Therefore, only aluminium can be used in pure form.
(b) Improved
corrosion resistance can be obtained by adding corrosion resistant elements.
For example inter-granular corrosion occurs in stainless steel. This tendency
can be reduced by addition of small amount of titanium.
(c) Nickel, copper and their alloys are used in
non-oxidizing environment, whereas chromium containing alloys are used in
oxidizing environment.
(d) Materials
those are close in electrochemical series should be used for fabrication.
(e) Corrosive
materials are taken with suitable material of construction:
Corrosive material
|
Suitable material
|
Nitric acid
Hyfrofluoric acid
Distilled Water
Dilute sulphuric acid
Caustic
|
Stainless steel
Monel metal
Tin
Lead
Nickel
|
2. Proper design of equipment
Corrosion can be minimized in the
following conditions:
(a) Design
for complete drainage of liquids.
(b) Design
for ease of cleaning.
(c) Design
for ease of inspection and maintenance
(d) A
direct contact between two metals should be avoided. They may be insulated from
one another.
3. Coating or lining
Corrosion resistant coating may be
applied on metal surface to improve corrosion resistance. It also separates the
metal from corrosive environment.
(a) Organic coating are used as
lining in equipment such as tanks, piping,
FERROUS MATERIAL
Cast Iron, Steels, Stainless Steels
Cast Iron
This iron consists of carbon more than 1.5%. Different
proportions of carbon gives different properties of the steel.
Properties:
1. Cast
iron is resistant to concentrated sulfuric acid, nitric acid and dilute
alkalis.
2. Cast
iron is attacked by dilute sulfuric acid, dilute nitric acid and dilute and
concentrated hydrochloric acid.
3. Cast
iron has low thermal conductivity.
4. It
is not corrosion resistance hence it is alloyed with Silicon, Nickel or
Chromium to produce corrosion resistacnce.
5. It
is brittle so it is tough to machine.
Applications:
1. It
is used as supports for plants.
2. Thermal
conductivity is low hence used as the outer wall of steam jacket.
3. It
is cheap hence used in place of more expensive materials by coating with enamel
or plastic.
Carbon Steel or Mild Steel
Mild steel (or carbon steel) is an iron alloy that contains
a small percentage of carbon (less than 1.5%).
Properties
1. It
has greater mechanical strength than cast iron.
2. It
is easily weldable.
3. Has
limited resistance to corrosion. This property can be increased by proper
alloying.
4. It
reacts with caustic soda, brine (concentrated NaCl solution).
Applications
1. Used
for construction of bars, pipes and plates.
2. Used
to fabricate large storage tanks for water, sulfuric acid, organic solvents
etc.
3. Used
as the supporting structures of grinders and bases of vessels.
Stainless Steel
Stainless steel is an alloy of iron usually of nickel and
chromium.
For pharmaceutical use stainless steel contains 18% chromium
and 8% nickel. This steel is called 18/8 stainless steel.
Properties:
1. It
is heat resistant
2. Corrosion
resistant
3. Ease
of fabrication
4. Cleaning
and sterilization is easy.
5. Has
good tensile strength.
6. During
heat welding the corrosion resistant properties of stainless steel may be
reduced du to deposition of carbide precipitate at the crystal grain
boundaries. This steel is stabilized by addition of minor quantities of
titanium, molybdenum or niobium.
Applications:
1. Storage
and extraction vessels, evaporators and fermenting vessels.
2. Small
apparatus like funnels, buckets, measuring vessels.
3. Sinks
and bench tops.
4. In
penicillin production plant nearly all equipment are made of stainless steel.
ALUMINIUM
Properties:
1. Pure
aluminium is soft and more corrosion resistant than its alloys. Small
percentages of manganese, magnesium or silicon produces strong, corrosion
resistant aluminium alloys (e.g Duralumin)
2. It
is attacked by mineral acids, alkali, mercury and its salts.
3. It
is resistant to strong nitric acid.
4. It
is resistant to acetic acid due to the formation of a gelatinous surface film
of aluminium subacetate.
5. Low
density hence lighter.
Applications:
1. The
salts of aluminium is colorless and non-toxic to microorganisms, hence used for
fermenting vessels for biosynthetic production of citric acid, gluconic acids
and streptomycin.
2. Used
for making extraction and absorption vessels in preparation of antibiotics.
3. Storage
vessels of acetic acid and ammonia.
4. Plants
for nitric acid is used.
5. Because
of its lightness large containers such
as drums, barrels, road and rail tankers are made with aluminium.
GLASS
Preparation of glass:
 |
Glass is composed principally of sand (silica - SiO2),
soda-ash (Na2CO3 - sodium carbonate) and lime-stone (Ca
CO3-calcium carbonate).
Glass made from pure silica consists of a three-dimensional
network of silicon atoms each of which is surrounded by four oxygen atoms an in
this way the tetrahedra are linked together to produce the network.
Glass prepared from pure silica require very high
temperature to fuse, hence soda-ash and lime is used to reduce the melting
point.
(i) glass made of pure silica has network (Fig-1)
Properties:
(a) It
is very hard and
(b)
chemically resistant but
(c)
melting point very high so it is very difficult to mould.
(ii) Glass made of pure silica + Na2O (Fig.-2)
(valency
of Na = 1)
Properties:
(a)Structure
is less rigid so low
m.p. and easier to mould
(b) the
glass is too rapidly attacked
by water and NaOH is leached out of the
glass.
(iii) Pure silica + CaO (or BaO, MgO, PbO and ZnO) (Fig.-3)
(valency
of Ca, Ba, Mg, Pb, Zn = 2)
Properties:
(a)
divalent oxides do not break the network
of pure
silica, but only push the tetrahedron
apart.
It is more rigid than soda-silica network.
(b)
Since the bond is more stronger, hence chemical reactivity is lowered.
(iv) Pure silica + Boric(B2O3) or
aluminium oxide (Al2O3)
(valency
of B and Al = 3, i.e. trivalent)
(a) Since boric oxide, like silica, is acidic. it does not
disrupt the network of silica but forms tetrahedron itself; however, these are
not the same size as the silicon tetrehedra; as a result the lattice become
distorted, and this produces flexibility.
(b) It is chemically resistant.
Type of glass
|
Main Constituents
|
Properties
|
Uses
|
Type-1
Borosilicate glass
e.g. Pyrex, Borosil
|
SiO2 - 80%
B2O3 - 12
Al2O3 - 2%
Na2O+CaO - 6%
|
·
Has high melting point so can withstand high
temperature
·
Resistant to chemical substances
·
Reduced leaching action
|
·
Laboratory glass apparatus
·
For injections and
·
for water for injection.
|
Type-II
Treated soda-lime glass
|
Made of soda lime glass. The surface of which is treated
with acidic gas like SO2 (i.e. dealkalised) at elevated
temperature (5000C) and moisture.
|
·
The surface of the glass is fairly resistant
to attack by water for a period of time.
·
Sulfur treatment neutralizes the alkaline
oxides on the surface, thereby rendering the glass more chemically resistant.
|
·
Used for alkali sensitive products
·
Infusion fluids, blood & plasma.
·
large volume container
|
Type-III
Regular soda-lime glass
|
SiO2
Na2O
CaO
|
·
It contains high concentration of alkaline
oxides and imparts alkalinity to aqueous substances
·
Flakes separate easily.
·
May crack due to sudden change of temperature.
|
·
For all solid dosage forms (e.g. tablets,
powders)
·
For oily injections
·
Not to be used for aqueous injection
·
Not to be used for alkali-sensitive drugs.
|
Type NP
Non-parenteral glass or General purpose soda-lime glass.
|
·
For oral and
·
Topical purpose
·
Not for ampoules.
|
||
Neutral Glass
|
SiO2 - 72-75%
B2O3 - 7-10%
Al2O3 - 6%
Na2O - 6-8%
K2O - 0.5 - 2%
BaO - 2-4%
|
·
They are softer and can easily be moulded
·
Good resistance to autoclaving
·
Resistant to alkali-preparations (with pH upto
8)
·
Lower cost than borosilicate
|
·
Small vials (<25 ml)
·
Large transfusion bottles
|
Neutral Tubing for
Ampoules
|
SiO2 - 67%
B2O3 - 7.5%
Al2O3 - 8.5%
Na2O - 8.7%
K2O - 4%
CaO - 4%
MgO - 0.3%
|
·
In comparison to neutral glass its melting
point is less. After filling the glass ampoules are sealed by fusion and
therefore the glass must be easy to melt.
|
·
Ampoules for injection.
|
  Colored
glass |
Glass + iron oxide
|
·
Produce amber colour glass
·
Can resist radiation from
290 400 450nm
UV Visible
|
·
For photosensitive products.
|
Advantages of glass
container
Physical aspect
1.
They are quite strong and rigid.
2.
They are transparent which allows the visual inspection
of the contents; especially in ampoules and vials.
3.
They are available in various shapes and sizes.
Visually elegant containers attracts the patients.
4.
Borosilicate (Type-I) and Neutral glasses are resistant
to heat so they can be readily sterilised by heat.
5.
Glass containers can be easily cleaned without any
damage to its surface e.g. scratching or bruising.
Chemical aspect
6.
Borosilicate type of glass is chemically inert. Treated
soda lime glass has a chemically inert surface.
7.
As the composition of glass may be varied by changing
the ratio of various glass constituents the proper container according to
desired qualities can be produced.
8.
They do not deteriorate with age, if provided with
proper closures
9.
Photosensitive drugs may be saved from UV-rays by using
amber colour glass.
Economical aspect
10.
They are cheaper than other packaging materials.
Disadvantages:
Physical aspect
1.
They are brittle and break easily.
2.
They may crack when subject to sudden changes of
temperatures.
3.
They are heavier in comparison to plastic containers.
4.
Transparent glasses gives passage to UV-light which may
damage the photosensitive drugs inside the container.
Chemical aspect
5.
Flaking: From
simple soda-lime glass the alkali is extracted from the surface of the
container and a silicate rich layer is formed which sometimes gets detached
from the surface and can be seen in the contents in the form of shining plates -
known as ‘flakes’ and in the form of needles
- they are known as
‘spicules’. this is a serious problem, specially in parenteral preparations.
6.
Weathering:
Sometimes moisture is condensed on the surface of glass container which can
extract some weakly bound alkali leaving behind a white deposit of alkali
carbonate to remain over there, further condensation of moisture will lead to
the formation of an alkaline solution which will dissolve some silica resulting
in loss of brilliance from the surface of glass - called weathering.
To
prevent weathering, the deposited white layer of alkali carbonates should be
removed as early as possible by washing the containers with dilute solution of
acid and then washing thoroughly with water.