ASPIRIN

Aspirin also known as acetylsalicylic acid is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. Aspirin was first isolated by Felix Hoffmann, a chemist with the German company Bayer, under the direction of Arthur Eichengrn. Salicylic acid, the main metabolite of aspirin, is an integral part of human and animal metabolism. While in humans much of it is attributable to diet, a substantial part is synthesizedendogenously. Aspirin also has an antiplatelet effect by inhibiting the production of thromboxane, which under normal circumstances binds platelet molecules together to create a patch over damaged walls of blood vessels. Because the platelet patch can become too large and also block blood flow, locally and downstream, aspirin is also used long-term, at low doses, to help prevent heart attacks, strokes, and blood clot formation in people at high risk of developing blood clots. It has also been established that low doses of aspirin may be given immediately after a heart attack to reduce the risk of another heart attack or of the death of cardiac tissue. Some people take a daily aspirin to reduce their risk of heart attack. New evidence suggests that aspirin may be a powerful tool in cancer prevention as well. The main undesirable side-effects of aspirin taken by mouth are gastrointestinal ulcers, stomach bleeding, and tinnitus, especially in higher doses. In children and adolescents, aspirin is no longer indicated to control flu-like symptoms or the symptoms of chickenpox or other viral illnesses, because of the risk of Reye's syndrome. Aspirin is part of a group of medications called nonsteroidal anti-inflammatory drugs (NSAIDs), but differs from most other NSAIDS in the mechanism of action. Though it, and others in its group called the salicylates, have similar effects (antipyretic, anti-inflammatory, analgesic) to the other NSAIDs and inhibit the same enzyme cyclooxygenase, aspirin (but not the other salicylates) does so in an irreversible manner and, unlike others, affect more the COX-1 variant than the COX-2 variant of the enzyme. Today, aspirin is one of the most widely used medications in the world, with an estimated 40,000 tonnes of it being consumed each year.In countries where Aspirin is a registered trademark owned by Bayer, the generic term is acetylsalicylic acid (ASA).

USES
Aspirin is used in the treatment of a number of conditions including: fever, pain, rheumatic fever, and inflammatory diseases, such as rheumatoid arthritis, pericarditis, and Kawasaki disease. It is used by those at high risk to prevent transient ischemic attacks, strokes, heart attacks, pregnancy loss, and cancer. Its use by those at low risk of heart problems is not advised however, as any beneficial effect is offset by increased risks of bleeding. PAIN In general, aspirin works well for dull, throbbing pain; it is ineffective for pain caused by most muscle cramps, bloating, gastric distension, and acute skin irritation.The most studied example is pain after surgery, such as tooth extraction, for which the highest allowed dose of aspirin (1 g) is equivalent to 1 g of paracetamol (acetaminophen), 60 mg of codeine, or 5 mg of oxycodone. A combination of aspirin andcaffeine, in general, affords greater pain relief than aspirin alone. Effervescent aspirin alleviates pain much faster than aspirin in tablets (1530 min vs. 4560 min). Nevertheless, as a postsurgery painkiller, aspirin is inferior to ibuprofen and has higher gastrointestinal toxicity. The maximum dose of aspirin (1 g) provides weaker pain relief than an intermediate dose of ibuprofen (400 mg), and this relief does not last as long. A combination of aspirin and codeine may have a slightly higher analgesic effect than aspirin alone, however, this difference is not clinically meaningful. It appears ibuprofen is at least equally, and possibly more, effective than this combination. According to a 1998 meta-analysis of clinical trials for menstrual pain, aspirin demonstrated higher efficacy than placebo, but lower than ibuprofen or naproxen, although maximum doses of aspirin were never used in these trials. The authors concluded that ibuprofen has the best risk-benefit ratio. Aspirin did not ease pain during cycling exercise, while caffeine was very effective. Likewise, aspirin, codeine, or paracetamol was not better than placebo for muscle soreness after exercise. HEADACHE Aspirin is a first-line drug in the treatment of migraine, bringing relief in 5060% of the cases.When used at a high dose of 1000 mg (as compared to 275325 mg when used as a pain killer or 81 mg (the dose of baby-strength aspirin) as an antiplatelet therapy), no significant differences were seen as compared to triptan medication, sumatriptan (Imitrex) and other painkillers such as paracetamol (acetaminophen) or ibuprofen. The combination of aspirin, paracetamol (acetaminophen) and caffeine (as found in the OTC brand Excedrin) is even more potent. For the treatment of migraine headache, this formulation works better than any of its three components taken separately better than ibuprofen and better than sumatriptan. As with all other medications for migraine, it is recommended to take aspirin at the first signs of the headache, and it is the way these medications were used in the comparative clinical trials. Aspirin alleviates pain in 6075% of patients with episodic tension headaches. It is equivalent to paracetamol (acetaminophen) in that respect, except for the higher frequency of gastrointestinal sideeffects. Comparative clinical trials indicated metamizole and ibuprofen may relieve pain faster than aspirin, although the difference becomes insignificant after about two hours. The addition of caffeine in a dose of 60130 mg to aspirin increases the analgesic effect in headache. The combination of aspirin, paracetamol (acetaminophen) and caffeine is still more effective, but at the cost of more stomach discomfort, nervousness and dizziness. There is some evidence low-dose aspirin has benefit for reducing the occurrence of migraines in susceptible individuals.

CHEMICAL PROPERTIES
Acetylsalicylic acid decomposes rapidly in solutions of ammonium acetate or of the acetates, carbonates, citrates or hydroxides of the alkali metals. Acetylsalicylic acid is stable in dry air, but gradually hydrolyses in contact with moisture to acetic and salicylic acids. In solution with alkalis, the hydrolysis proceeds rapidly and the clear solutions formed may consist entirely of acetate and salicylate. Aspirin, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance, with a melting point of 135 C (275 F).

SYNTHESIS
The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acid's hydroxyl group into an ester group (R-OH R-OCOCH3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction. Small amounts of sulfuric acid (and occasionally phosphoric acid) are almost always used as a catalyst. This method is commonly employed in undergraduate teaching labs.

Reaction Mechanism

Formulations containing high concentrations of aspirin often smell like vinegar because aspirin can decompose through hydrolysis in moist conditions, yielding salicylic acid and acetic acid. The acid dissociation constant (pKa) for acetylsalicylic acid is 3.5 at 25 C (77 F).

POLYMORPHISM
Polymorphism, or the ability of a substance to form more than one crystal structure, is important in the development of pharmaceutical ingredients. Many drugs are receiving regulatory approval for only a single crystal form or polymorph. For a long time, only one crystal structure for aspirin was known, although there had been indications aspirin might have a second crystalline form since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005, and fine structural details were given by Bond et al.A new crystal type was found after attempted cocrystallization of aspirin and levetiracetam from hot acetonitrile. The form II is only stable at 100 K and reverts to form I at ambient temperature. In the (unambiguous) form I, two salicylic molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds, and in the newly claimed form II, each salicylic molecule forms the same hydrogen bonds with two neighboring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups both polymorphs form identical dimer structures.