Factors Affecting Materials Selected For Pharmaceutical Plant Construction

Factors Affecting Materials Selected For Pharmaceutical Plant Construction


Several variables influence the decision of selecting the best material for construction for any plant. In some cases, the root cause of metal corrosion is a selection of materials that are inherently incompatible with the environment. In other cases, corrosion is a result of mechanical design, where incompatible metals are joined together or components meet in a manner that results in narrow spaces between the components. Corrosion can also be the result of faulty manufacturing processes that result in microstructures that render an alloy susceptible to corrosion. The three major variables are corrosion resistance, cost, and expected operating life. There are other minor variables such as the compatibility of the material of construction with existing plant installations, plant operating conditions, ease of maintenance, and cleaning requirements to name a few. While these are less critical, they are still important to keep in mind as you establish the criteria for a particular plant. The selection of a material for the construction of equipment depends on the following factors:


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 or the product may destroy the material of construction.


(a) Contamination of product: Iron contamination may change the color of the products (like gelatin capsule shells), and catalyze some reactions that may enhance the rate of decomposition of the product. Leaching of glass may make the aqueous product alkaline. This alkaline medium may catalyze the decomposition of the product. Heavy metals such as lead inactivate penicillin.


(b) Destruction of material of construction: The products may be corrosive. 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. It is important to know what chemicals are to be processed. Selection should be done consciously and while selecting appropriate materials that comply with the chemical composition of the process it should be ensured that it will perform to the expectations.


(c) Chemical inertness: Aggressive reaction environments tend to dissolve metals from unlined mild steel or alloy reactors. Extractable metals, such as chromium, nickel, molybdenum, and copper, can leach into and contaminate products, producing undesired catalytic effects that can cause harmful fluctuations in the process reactions. These metals can compromise product quality, negatively affect product yield, and in some cases even cause runaway reactions.


Physical Factors

(a) Strength: The material should have the sufficient physical strength to withstand the required pressure and stresses. Iron and steel possess these properties. Tablet punching machine, die, upper and lower punches are made of stainless steel to withstand very high pressure. Glass though has strength but is brittle. The aerosol container must withstand very high pressure, so tin plate containers coated with some polymers (lacquered) are used. Plastic materials are weak so they are used in some packaging materials, like blister packs.


(b) Mass: For transportation purposes light weight packaging materials are used. Plastic, aluminum, and paper packaging materials are used for packing pharmaceutical products.


(i) 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 are required ceramic and iron grinding surfaces are not used.


(ii) 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.


(iii) Thermal expansion: If the material has a very high thermal expansion coefficient then as temperature increases the shape of the equipment changes. This produces uneven stresses and may cause fractures. In such cases, materials used should be able to maintain the shape and dimensions of the equipment at the working temperature conditions.


(iv) Ease of fabrication: During the fabrication of equipment, the materials undergo various processes such as casting, welding, forging and mechanization, etc. For example, glass and plastic may be easily molded into containers of different shapes and sizes. Glass can be used as a lining material for reaction vessels.


(v) Cleaning: Some materials of construction can pose housekeeping issues when it comes to ease of cleaning. A smooth and polished surface makes cleaning easier. Glass with an anti-adhesive and nonporous surface resists the build-up of viscous or sticky products. Borosilicate glass is a popular choice for processes where ease of cleaning is critical. Upon completion of an operation, the equipment is cleaned thoroughly to avoid contamination of the previous product into the next product. Glass and stainless steel surfaces are generally smooth and polished and are easy to clean.


(vi) Sterilization: The ideal feature of glass, transparency, allows us to see when equipment needs to be cleaned without the need for interrupting the process and performing an internal inspection. In the production of parenteral, ophthalmic, and bulk drug products all the equipment is required to be sterilized. This is generally done by introducing steam under high pressure. The materials must withstand this high temperature (121°C) and pressure (15 lb/inch2 ). If rubber materials are being used they should be vulcanized to withstand the high temperature.


(vii) Transparency: Unlike most plastic and metal materials, glass equipment provides transparency to give an unobstructed view of what is going on inside the system, enhancing the observation of the process. In reactors and fermenters, a visual port is provided to observe the progress of the process going on inside the chamber. For this purpose, borosilicate glass is often used. In parenteral and ophthalmic containers the particles, if any, are observed from polarized light. The walls of the containers must be transparent to see through them. In this case, glass is the most preferred material of choice. For photosensitive substances, brown-coated glass is also available to offer extra protection. If there is concern over potential mechanical stresses inflicted on the glass, Sectrans coating is applied. This coating covers the glass surface and provides protection against scratches, blows, and splintering.


Economic Factors

The owner’s budget is very important. The initial cost of the equipment depends on the material used. Several materials may be suitable for construction from physical and chemical points of view, but from all the materials only the cheapest material is chosen for the construction of the equipment. Materials that require lower maintenance costs are used because in long run it is economical. Thus, capital expenditures need to be taken into consideration to ensure that the cost does not exceed the financial limits.


Expected Operating Life

Although operational life is less critical, they are still important to keep in mind as we establish the criteria for the plant. It is important to know how long we plan to keep the system in operation. Whether it’s a continuous or batch process, how frequently it is run, and how many years of service we hope to get out of it are all questions that need to be accounted for when determining the type of system components to employ.


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