11
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MATERIALS OF PHARMACEUTICAL PLANT CONSTRUCTION
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Selected Definitions Thermoplastic:
They get softened with application of pressure and heat but regain their original shape on cooling.
Thermosetting:
They are permanently shaped to rigid structure when pressure and heat is applied.
Blooming or weathering: When glass wares are stored over a month in damp atmosphere having variations in temperature. Due to this, salts leach out of glass and appear as fine crystals.
11.1 INTRODUCTION For manufacturing of pharmaceuticals, bulk drugs etc, number of equipments are used. The equipments are generally used for processing and packing of products. A wide variety of materials are used for manufacturing of theses equipments. Some products are highly acidic while some are highly alkaline. Some products such as storage of biological products need to be handled carefully. Therefore design of equipment, material selection and fabrication technique need to be considered carefully. These factors affects the success or failure of new chemical plant. If container will not compatible with material then there are chances of contamination. The proper choice of material is very important. The choice based on expert advice, previous experience and laboratory tests. The material used for construction of plant is classified as metals (ferrous and non ferrous) and non metals (organic and inorganic).
11.2 FACTORS AFFECTING DURING MATERIALS SELECTED FOR PHARMACEUTICAL
PLANT CONSTRUCTION
The selection of a material for the construction of the equipment depends on the following properties
1.
2.
Chemicalfactors a.
Contamination of the product
b.
Corrosion of material of construction
Physicalfactors a.
Strength
b.
Mass
c.
Wear properties
d.
Thermal conductivity
e.
Thermal expansion
f.
Ease of fabrication 73
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3.
g.
Cleaning
h.
Sterilization
1.
Transparency
Pharmaceutical
Engineering
Economic factors
11.2.1 Chemical Factor Each time a chemical is placed in a container or equipment, the chemical is exposed to the construction material of the container or equipment. Therefore, the construction material can contaminate the product or the product can destroy the construction.
a.
Product contamination:
Iron contamination can change the color of products (such as gelatin capsules), catalyze some reactions that can increase the decomposition rate of the product. The leaching of glass can make the aqueous product alkaline. This alkaline medium can catalyze the decomposition of the product. Heavy metals, such as lead, inactivate penicillin.
b.
Corrosion of construction material:
The products can be corrosive in nature. They can react with the material and can destroy it. This cause decrease the life of the equipment. Extreme pH, strong acids, strong alkalis, powerful oxidizing agents, tannins, etc., they reacts with the materials, therefore, some alloys that have a special chemical resistance are used.
11.2.2 Physical factors a. Strength: The material must have sufficient physical strength to withstand the pressure and stress required. Iron and steel can satisfy these properties. The tablet punching machine, the die and the upper and lower punches are made of stainless steel to withstand very high pressure. The glass, although it has strength but is fragile. The aerosol container must withstand very high pressure, so tin containers covered with some polymers are used. The plastic materials are weak, so they are used in some packaging materials, such as blister packs.
b. Mass: For transportation, lightweight packaging materials are used. Plastic, alurninum and paper packaging materials are used to package pharmaceutical products.
c.
Wear properties: When there is a possibility of friction between two surfaces, the softer surface disappears and these materials contaminate the products. For example, during milling and grinding, grinding surfaces can wear out and contaminate the powder. When pharmaceutical products of very high purity are required, grinding surfaces of ceramic and iron are not used.
d. Thermal conductivity: In evaporators, dryers, stills and heat exchangers, the materials used should
e.
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 a very high coefficient of thermal expansion then as the temperature increases, the shape of the equipment changes. This produces unequal stresses and can
Materials of pharmaceutical plant construction
f.
g.
h.
i.
175
cause fractures. Therefore, materials that are capable of maintaining the shape and dimension of the equipments at the working temperature should be used. Ease of fabrlcadon: During the manufacturing of equipment, the materials undergo various processes, such as casting, welding and forging. For example, glass and plastic can be easily molded into containers of different shapes and sizes. The glass can be used as a coating material for reaction vessels. Cleaning: Smooth and polished surfaces facilitate ease in cleaning. After completing the operation, the equipment is thoroughly cleaned so that the previous product can not contaminate the next product. The surfaces of glass and stainless steel can be smooth and polished. Sterilization: In the production of parenterals, ophthalmic and bulk drugs, all equipment must be sterilized. This is usually done by introducing high pressure steam. The materials must withstand at high temperature (1210 C) and pressure (15 pounds per square inch). If there are rubber materials, it must be vulcanized to withstand the high temperature. Transparency: In the reactors and fermentors a visual port is provided to observe the progress of the process that takes place inside the chamber. In this case, borosilicate glass is often used. In parenteral and ophthalmic containers, the particles, if any, are observed with polarized light. The walls of the containers must be transparent to see through it. The glass is used as perfect material.
11.2.3 Economic factors The initial cost of the equipment depends on the material used. Several materials may be suitable for construction from the physical and chemical point of view, but of all the materials only the cheapest material for the construction of the equipment is chosen. Materials that require a lower maintenance cost are used because in the long term it is economical.
11.3 CLASSIFICATION OF MATERIAL FOR PLANT CONSTRUCTION Material
I Organic ~Rubber LplaStic
used for construction
I
I
Non Metals
Metals
I
I
I
Inorganic
Ferrous
t
Glass Glassed steel
Figure 11.1: classification
t
Non ferrous
Cast Iron
~
Carbon
L Lead
steel
Aluminium
Stainless steel
of material used for construcdon
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Pharmaceutical
Engineering
NON METALS-ORGANIC 11.4 RUBBER It is used as lining material 1.
Latex:
Advantages: The latex is ready to use directly outside the container. Latex is economical, exhibits good abrasion resistance and is an elastic moldable rubber. Latex molds are also good for casting wax and gypsum. Disadvantages: Low-cost latex products generally shrink. Making molds with latex rubber is slow and time consuming. Latex molds are generally not suitable for melting resins. 2. Polysulfide rubber Advantages: years.
:
The polysulfide molds are very soft, "elastic" and long lasting, some have a useful life of 40
Disadvantages: It has an offensive smell. The polysulfides must be accurately mixed by weight otherwise they will not work. Polysulfide rubber costs more than latex. 3. Silicone rubbers: Advantages: Silicone rubber has the best release properties of all mold rubbers. The combination of good release properties, chemical resistance and heat resistance makes silicone the best choice for the production of resin castings. Disadvantages:
The silicones generally have a high cost.
4. Polyurethane
rubbers:
Advantages:
Polyurethanes are easy to use. They are less expensive than silicones and polysulphides.
Disadvantages: As silicone rubber has the best release properties, urethane rubber has the worst release properties and adheres to almost anything. They have limited shelf life after opening.
11.5 PLASTIC Plastic is commonly used material. It is light in weight. In plastic there are no chances of contamination as in metallic container. They are available in variety of shapes. But plastic is not preferred in case of higher temperature. Generally pipes and tubing are made of plastic material. They are used for storage of inorganic salt and weak acid. They can be easily cut as per requirement. Plastic do not corrode in air or water. It is also used as insulating material.
11.5.1 Types: 1.
Thermoplastic: They get softened with application of pressure and heat but regain their original shape on cooling.
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Different type of thermoplastic Thermoplastics Polvethvlene Polypropvlene
2.
and their uses
Uses . Cables, buckets, pines Milk cartons, ropes
Teflon (fluorocarbons)
Gaskets, coating
Polvvinylchloride (PVC)
Manufacture of Gloves
Thermosetting: They are permanently shaped to rigid structure when pressure and heat is applied. Example Phenol-formaldehyde. They cannot withstand on severe abrasion.
NON METALS-INORGANIC 11.6 GLASS Glass container is widely used in daily life. It is composed of sand (pure silica), soda ash (sodium carbonate), limestone (calcium carbonate) and cullet (broken glass). Cullet act as fusion agent for whole mixture. Glass in its solid state is considered as supercooled liquid.
11.6.1 Types There are different varieties of glasses are used such as 1.
Soft glass: They are made of sodium silicate and calcium silicate. It is used for making glass bulbs and window glasses.
2.
Hard Glass: They are made of potassium silicate and calcium silicate. They are used for making glass apparatus
3.
Flint Glass: They are made of potassium silicate and lead silicate.
4.
Quartz glass: They are made of pure silica. They are used for making silica crucible.
5.
Pyrex Glass and Jena glass: They are generally used laboratory glasswares. The iron oxide is added to give amber colored glass but iron oxide could leach into stored products.
There are 4 type of glasses used in pharma industry IP 1.
Type I (Borosilicate glass): It is highly resistant to alkali leaching. In this alkali and earth cations are replaced by boron. They are less brittle. Easy to clean and sterilize.
2.
Type 11 (Treated Soda Lime glass): In this type of glass, surface alkali is neutralized by sulfur dioxide vapors. They are used for making containers for buffered aqueous solution having pH below
7. 3.
Type III (soda lime glass): It release 10 times more alkali than type I and type IT glass. It offers moderate hydrolytic resistance. It is used for dry powder and oleaginous solutions.
4.
Type IV (General purpose soda lime glass): It is not used for parenterals. It is used as container for tablets, oral solutions, suspensions, ointment and liquid for external use.
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Pharmaceutical
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When glasswares are stored over a month in damp atmosphere having variations in temperature. This cause Blooming or weathering. As a result salts leach out of glass and appear as fine crystals. In this case salt is washed off with water and acid. Pharmaceutical glass containers should comply with official test for hydrolytic resistance. -
11.6.2 Advantages of glass: 1. 2. 3. 4. 5. 6.
Attractive in appearance Available in variety of size, shapes and colors. Inert Cheap Does not deteriorate with age. Amber colored glass protect against light.
11.6.3 Disadvantage: 1.
Fragile in nature and damaged by thermal shock
11.7 GLASSED STEEL It is inorganic product of fusion. It is cooled to rigid condition without crystallizing. They are used in heavy vessels. It has excellent resistant to all acids. This is suitable in case of transparent pipes. Ferrous metals They are widely used as construction material because it is mechanically economical.
strong, easy available and
11.8 CAST IRON It is the combination of iron with carbon content greater than 2%. It is cheap and available easily so greater in demand. It is resistant to concentrated sulfuric acid, nitric acid and dilute alkalies. It has low thermal conductivity. The main disadvantage of cast iron is hard and brittle. Gray cast iron contain Carbon, silicone, Manganese and Selenium. It is easy to mold into any shape. Gray cast iron preven material from corrosion but it is not preventive against dilute acids. Malleable iron (white cast iron with carbon content 2.5%) is also available and it is also corrosion resistant. Nickel resistant cast iron have also superior toughness, easy to weld, corrosion and as well as heat resistant. A number of cast iron alloys like Duriron and Durichlor are available in market.
Uses: a.
It is used to jacketed steam pans
b.
It is used as lining material with plastic
11.9 CARBON STEEL It is an iron alloy having low percentage of carbon content. It is cheapest and easy to fabricate. It i versatile metal used in industry. It is easily weldable and excellent ductility, But carbon steel has limited
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resistant to corrosion and it also react with caustic soda. Low alloy steel has high mechanical strength. It contain 0.4% Carbon, 0.7% Manganese, 1.85% Nickel, 0.8% Chromium and 0.25% Molybdenum. The properties of carbon steel can be altered by alloying with Nickel, chromium and silicone. Carbon steelNickel alloy is tough and corrosion resistant. Carbon steel-chromium alloy increase hardness and more resistant to corrosion. At elevated temperature strength of carbon steel can be enhanced by preparing carbon steel-Molybdenum alloy. Uses: a.
It is used for construction of pipes and plates.
b.
It is used as supporting structure for plant vessels
c.
It is used as fabricating material for large storage tanks for water, sulfuric acid and organic solvents.
11.10 STAINLESS STEEL It is an alloy of iron. It contain 12 to 30% Chromium. 0 to 2% Nickel, low percentage of Carbon, Columbium, Copper, Molybdenum, Selenium, tantalum and titanium. It is widely used in industries because it is heat resistant, corrosion resistant, easily fabricated, and have high tensile strength. There are different type of stainless steel are available a.
Martensitic (type 410): It contain 12 to 20% chromium, 0.2 to 0.4% Carbon and 2% nickel. It is mild resistant to corrosion and organic exposure. It is less ductile. It is used to prepare sinks, bench tops, storage tanks and mixing elements.
b.
e-Ferrttlc (type 430): It contain 15 to 30% chromium and 0.1 % carbon. It is better resistant to corrosion. It is also resistant to oxidation and temperature. It is easy to machine. It is not good against reducing agents and hydrochloric acids. It is used in tower lining, baffles, heat exchangers, tubing, condensers, pump shafts and furnace parts.
c.
-Austenitic: It contain 13 to 20% chromium, 0.1 % <0.25% carbon and -22% nickel. It is highly corrosion resistant, easy to weld, easily clean and sterilized. It can be easily weld. It is used in fermentors, evaporators, storage vessels, extraction vessels.
d.
Others: Type 316, 316L and 317 with 2.5 to 3.5% Molybdenum are most corrosion resistant.
NON-FERROUS METALS 11.11 ALUMINIUM It is available in large number of alloys. Aluminum is cheap and light in weight. It has adequate mechanical strength. Their maintenance and cleaning is easy. Thermal conductivity of aluminium is 60% of pure copper. Its tensile strength is 10,000 lb/sq. in. It is resistant to corrosion. It can also used for concentrated nitric acid and acetic acid. It is used in wide variety of chemical equipments. But mechanical strength of aluminium decreases greatly above 150°C. For food and pharmaceutical uses super grade of Aluminium is used. It is used as container for storage of meat. It is used in heat transfer applications.
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Pharmaceutical Engineering
Aluminium alloy with improved mechanical properties and qualities are available which is also corrosion resistant. Aluminium-clad alloy is used for greater mechanical strength. Hot dipped aluminized steel is preferred when Sulfur is present. Aluminium is used in biosynthetic processes because it is non toxic to microorganism. . Uses: It is used for manufacturing of container (tanks), rail tankers and barrels.
11.12 LEAD In pharmaceutical industry, lead is used in less percentage because in large amount it produce toxicity. It is cheap. It is generally used for non food products. The addition of Silver (Ag) and Copper (Cu) make lead corrosion resistant and fatigue resistant. Lead has poor structural quality due to low melting point. Therefore antimony is added to hardens the lead. Lead pipes are used for solutions containing sulfuric acid. The main disadvantage of lead is high coefficient of expansion which may cause permanent deformation.
11.13 OTHERS a.
Copper and its alloy are also used in chemical processing because it has low temperature properties.
b.
Nickel and its alloy are also used for handling alkalies and storing and shipping of high purity caustic soda and potash. It is also used to store chlorinated solvents and phenol.
c.
Titanium is also used as construction material due to strong, corrosion resistant, resistant to hot chloride solutions and nitric acid. But it is costly.
CllEVIEW VERY SHORT ANSWER OUESTIO Q1. Define Thermosetting
QUESTIONS
T~
plastic
Answer- They are permanently shaped to rigid structure when pressure and heat is applied Q2. What are Type I glass? Answer- they are Borosilicate glass. It is highly resistant to alkali leaching. In this alkali and earth cations are replaced by boron. They are less brittle. Easy to clean and sterlize. Q3. What are Hard Glass? Answer- They are made of Potassium silicate and calcium silicate. They are used for making glass apparatus. Q4. Write composition of Martensitic (type 410). Answer- It contain 12 to 20% chromium, 0.2 to 0.4% Carbon and 2% nickle. QS. Define Blooming or weathering. Answer- When glasswares are stored over a month in damp atmosphere having variations in temperature. As a result salts leach out of glass and appear as fme crystals.
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SHORT ANSWER QUESTIONS Q1. Why Stainless Steel is used as construction material in industries? Answer- It is an alloy of iron. It contain 12 to 30% Chromium, 0 to 2% Nickel, low percentage of Carbon, Columbium, Copper, Molybdenum, Selenium, tantalum and titanium. It is widely used in industries because it is heat resistant, corrosion resistant, easily fabricated, and have high tensile strength. Q2. Write importance of glassed steel in pbarma industry. Answer- It is inorganic product of fusion. It is cooled to rigid condition without crystallising. They are used in heavy vessels. It has excellent resistant to all acids. Suitable in case of transparent pipes. Q3. Explain different types of glasses used in pbarma industry. Answer- There are 4 type of glasses used in pharma industry IP I. Type I (Borosilicate glass): It is highly resistant to alkali leaching. In this alkali and earth cations are replaced by boron. They are less brittle. Easy to clean and sterilize. 2. Type n (Treated Soda Lime glass): In this type of glasses, surface alkali is neutralized by sulfur dioxide vapors. These are used for making containers for buffered aqueous solution having pH below 7. 3. Type ill (soda lime glass): It release 10 times more alkali than type I and type II glass. It offer moderate hydrolytic resistance. It is used for dry powder and oleaginous solutions. 4. Type IV (General purpose soda lime glass): It is not used for parenterals. It is used as container for tablets, oral solutions, suspensions, ointment and liquid for external use. Q4. Describe usefullness of Nickle and its aUoy. Answer- They are used for handling alkalies and storing and shipping of high purity caustic soda and potash. It is also used to store chlorinated solvents and phenol. Q5. Write advantages and disadvantages of Silicone rubbers. Answer- Advantages: silicone rubber has the best release properties of all mold rubbers. The combination of good release properties, chemical resistance and heat resistance makes silicone the best choice for the production of resin castings. Disadvantages: silicones generally have a high cost.
LONG ANSWER QUESTIONS Q I. Explain the factors which should be considered during selection of material for pharmaceutical plant construction. (Refer article 11.2) Q2. Write detailed note on rubber as material for plant construction (Refer article 11.4) Q3. Write detailed note on a. Plastic b. Glass (Refer article 11.5, 11.6) Q4. Define stainless steel. Explain the properties of different types of stainless steel used? (Refer article 11.10) Q5. Discuss the application, advantages and disadvantages of Aluminium (Refer article 11.11) Q6. Write note on a. Advantages of glass (Refer article 11.6.2) b. Lead as construction material (Refer article 11.12) c. Types of plastic (Refer article 11.5.1)
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MULTIPLE 1.
Pharmaceutical
CHOICE OUESTIONS
Which of the following is not a physical factors affecting during selection of materiais for Phannaceutical plant construction?
2.
3.
4.
5.
a. Mass
b. Wear properties
c. Thermal conductivity
d. Corrosion of material of construction
Which of the following metal is used as construction material a. Cast iron
b. Glass
c. Rubber
d. Plastic
Addition of
produce amber colored glass
a. iron oxide
b. Zinc oxide
c. Magnesium oxide
d. Aluminum oxide
Which of the following glass are made of potassium silicate and lead silicate? a. Soft glass
b. Flint glass
c. Hard glass
d. Quartz glass
Soft glass are made of a. sodium silicate and calcium silicate. b. Potassium silicate and calcium silicate c. Potassium silicate and magnesium silicate d. Pure silica
6.
Borosllicate glass is also known as a. Type I
b. Type IT
c. Type ill
d. Type IV
7. Which of the following IsI are of cast iron aDoys avaDable in market a. Duriron b. Durichlor c. Both a and b 8.
9.
Engineering
d. Duradenn
Which of the following lsIare of the type of stainless steel a. Martensitic
b. Ferritic
c. Austenitic
d. All of the above
The tensile strength of Aluminum is a. 10,000 lb/sq.in.
b. 200 lb/sq.in.
c. 20סס00 lb/sq.in
d. 50 lb/sq.in
ANSWERS l. d 2. a 3. a 4. b 5. a 6. a 7. c 8. d 9. a