Aspirin Production Process - Report Example

Aspirin Production Process Report Aspirin Production Process Report Introduction Aspirin is currently one of the most widely used and commercially available over the counter drugs in the world. This is attributed to the fact that the drug is currently one of the safest and least expensive non-prescription pain killers in the market. Although a number of other pain relievers have been discovered and manufactured even before the discovery of Aspirin, most of them only managed to gain acceptance as over the counter drugs after the success of aspirin at the beginning of the twentieth century. Currently the drug is widely used to treat a host of health problems including pain, inflammations, fever, cerebral thromboses, rheumatic fever, heart attacks, rheumatoid arthritis and gout. According to Zumdahl (2009, p.49), salicylic acid generally works by inhibiting the synthesis of certain hormones (prostaglandins) that are responsible for pain or inflammation in the human body. The use of the active ingredients of aspirin dates back to nearly 2500 years ago when the ancient Greeks documented that extracts of the bark of willow trees could successfully help relieve pain and other common symptoms of illnesses such as fever and inflammation (Sneader, 2000, p.1590). However, it was not until 1893 that the active ingredient of aspirin (acetylsalicylic acid) was first isolated and synthesized for therapeutic use by the two German scientists, Felix Hoffman and Arthur Eichengrün. This paper proposes a fine chemical (aspirin) production process based on a comprehensive review of recently published literature. Synthesis of Aspirin (Acetylsalicylic Acid) The proposed synthesis process primarily based on the stoichiometric reaction of salicylic acid and excess acetic anhydride in the presence of 85% phosphoric acid or concentrates sulphuric acid as catalysts. The reaction is exothermic and up to 84 kJ/mol of heat is normally released from the reactors operating in semi batch mode. Salicylic acid is a natural product that is commonly found in the bark of the willow tree. Although Salicylic acid is the precursor for aspirin, it is harsh on stomach linings and many people cannot tolerate its use in its pure form. For example, the corrosive nature of salicylic acid makes it unsuitable for human use because it causes gastric pain, attacks the mucous membrane of the mouth and causes a worse discomfort that was it is meant to cure (Leo, 2005, p.124). However, the derivative of Salicylic acid commonly known as aspirin or acetylsalicylic acid is relatively harmless and is currently manufactured both industrially and in the laboratory through a process known as esterification. Generally, esterification normally occurs when a carboxylic acid and an alcohol reacts together to form an ester. Although the actual production process of aspirin may vary between manufacturing and pharmaceutical companies, the key ingredients and the dosage forms fairly remain constant. For example, in the lab, a carboxylic acid (C6H4 (OH) COOH) and an alcohol (CH3CO) 2 O) are normally heated in the presence of a catalyst (Jeffreys, 2005, p.165). The main difference between the procedures used to synthesize acetylsalicylic acid in the laboratories and its industrial production is attributed to the scale of production. Modern pharmaceuticals have particularly developed a systematic process for the industrial production hundred of tons of acetyl salicylic acid (aspirin) annually. For example, compared to only a few grams required in the laboratory production of aspirin, industrial manufactures normally use several kilograms of the reactors in large reactors and storage containers. The other important considerations that are usually taken into account during industrial production include temperature, catalysts and the purity of the end product. In industrial production, the four main raw materials required for the manufacture of aspirin drugs include acetylsalicylic acid (active ingredient), water, corn starch and a lubricant. The industrial aspirin production process normally occurs in the two main parts of the aspirin industrial plant: Reactor Production recovery area Fig 1: Block Diagram of Aspirin Production Process Salicylic Acid Bins The Reactor The reactor is an important component of the aspirin production process where the major reactions will take place. The main reactor will be fitted with water cooled condenser, automatic temperature registers, thermometer and an efficient agitator. Additionally, the reactor should be easy to clean and sterilize. For a high quality product, all processes should be done at the specified temperatures. Efficient mixing of the mixture is required to expel air and manufacture a high quality product. Operators will be first required to pump several gallons of acetic anhydride from acetic anhydride storage tank. The stirrer (reaction agitator) is then turned on. A specified number of gallons of sulphuric acid or 85% phosphoric acid catalyst are then added to the mixture in the reactor. A number of precautions must however be observed during the reaction because dangerous chemicals are used. For example, acetic anhydride is corrosive and reacts violently with water. It has toxic fumes and is harmful when ingested. It is a lachrymator and causes the eye to hurt and water severely. Generally, reactions involving this chemical must be carried with sufficient caution. Salicylic acid causes skin irritations and can cause eye damage. Ethyl acetate and hexanes are flammable organic solvents. The reaction catalyst, phosphoric acid is strong and corrosive. It causes damage upon contact with any tissue. In most cases, the inside of the reactors are normally glass lined as a protective measure against acid reaction of the contents of the reactors. During the reaction, the water molecule spits off from the carboxylic acid and the remaining parts attach together to produce an ester as shown below: C6H4 (OH) COOH (Salicylic acid) + (CH3CO) 2O (Acetic anhydride)  CH3COOC6H4 COOH (Aspirin) + CH3COOH (Acetic acid). In this reaction, phosphoric acid is normally used as a catalyst. The OH group derived from the salicylic acid then reacts with acetic anhydride to form an ester. The carboxylic group of the salicylic acid however remains relatively unchanged. In the reaction, Salicylic acid will be acetylated by acetic anhydride and acetyl salicylic acid. Salicylic acid is 0-hydroxyl benzoic acid. It has both phenol functional group and carboxylic acid group. Acetic acid is the carboxylic acid and phosphoric acid is added as a catalyst while water is added to destroy any remaining acetic acid. The water adds across the anhydride bridge cleaving it and releasing two molecules of acetic acid. Lastly, the steam producing boilers section will have a number of pressure control valves to enable them control the temperatures of the reactor by releasing certain amounts of steam when pressure exceeds certain limits. The relationship between pressure and the steam temperature is that the boiling point of water is normally at the set pressure. The first reaction is reversible. The oxygen from the carbonyl of the acetic anhydride is generally protonated. The Electrophilicity of the carbon of the carbonyl is increased. The oxygen of the phenol in salicylic acid behaves as a nucleophile, attacks the carbon of the carbonyl within the acetic anhydride, and simultaneously breaks the π bond to oxygen. This forms a tetrahedral intermediate. A concurrent proton transfer occurs. This simultaneously makes the acetic acid to depart. After another proton transfer, the final aspirin is formed in a non-reversible reaction. The optimum temperature for the reaction is approximately between 88C and 92 C. The batch reaction cycle will be approximately 5hours and the reactors are will be kept at this temperature for up to 24hrs. The mixture will then be cooled gradually until it reaches room temperature of between approximately 15 and 25C. At this point, acetylsalicylic acid will begin to precipitate in the form of large and regular crystals. After successful reaction in the reactor, the contents should then be transferred to the crystallization chamber. Product Recovery Area (Crystallizer) The product recovery chamber also known as the crystallizer will be large vessel similar to the reactor with a capacity of about 12,000 gallons. After the reactants from the contents should then be transferred to the crystallization chamber, water will be pumped into the crystallizer before the agitator is also turned on. Brine (CaCl2 solution) of about -25C will then be added so as to bring the temperature of the mixture can reduced up to 5C. On the other hand, to drive the reaction equilibrium to its completion, excess acetic anhydride in relation to salicylic acid will be added the reactor. It is the excess acetic anhydride that will react exothermically with water in the crystallizer to form acetic acid. On the other hand, the temperatures at this stage will be kept at Read More