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1.1 Introduction 1.1 Introduction : Ibuprofen (from the now outdated nomenclature iso-butyl-propanoic- phenolic acid) is a non-steroidal anti-inflammatory drug (NSAID). It is a colorless crystalline solid widely used as an analgesic and anti-inflammatory medication. It is most commonly known as ibuprofen, but is also known as α-methyl-4-(2- methylpropyl) benzeneacetic acid and 4-isobutyl-@alpha;-methylphenylacetic acid. Originally marketed as Nurofen, Advil and Motrin and since then under various other trademarks, most notably Flamex, Profen, Inflam and Reumafen. It is also used for relief of symptoms of arthritis, primary dysmenorrhea, fever, and as an especially where there is an inflammatory component. Ibuprofen is known to have an antiplatelet effect, though it is relatively mild and short-lived when compared to that of aspirin or other more well-known antiplatelet drugs. Ibuprofen is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system. 2-(4-isobutylphenyl)propionic Acid (Ibuprofen) Figure: Structure of Ibuprofen Ibuprofen is a relatively safe drug. Because of its effectiveness and lack of side effects, these are now frequently prescribed by the Doctors. 1.2. According to Conventional drug: Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID). It is also a conventional drug. So ibuprofen is used in conventional treatment or therapy. 1.2.1.Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. 1.2.2. Conventional medicine: A system in which medical doctors and other healthcare professionals (such as nurses, pharmacists, and therapists) treat symptoms and diseases using drugs, radiation, or surgery. Also called Western medicine, mainstream medicine, orthodox medicine, biomedicine, and allopathic medicine. 1.2.3. Conventional drug Therapy: The short duration of activity is due to the inability of conventional dosage forms to control temporal delivery. If any attempt is made to maintain drug blood levels in the therapeutic range for longer periods by, for example increasing the initial dose of an intravenous injection, as shown by the dotted line in the figure, toxic level may be produce at early times. This approach is to administer the drug repetitively with a constant-dosing interval as in multiple dose therapy, which is shown below in figure for oral route; In this case the drug blood level reached and the time required to reach that level depend on the dose and the dosing interval. There are several potential problems inherent in multiple dose therapy. a) If the dosing interval is not appropriate for the biological half-life of the drug large “peak” and “valley” in the drug blood level may result, e.g. drugs with short half-lives require frequent dosing to maintain constant therapeutic levels. b) The drug blood level may not be within the therapeutic range at sufficiently early times an important consideration for certain disease states. c) Patients’ noncompliance with multiple dosing regimens can result in failure of this approach. In many instance, potential problem associated with conventional drug therapy can be overcome. When this is the case, drugs given in conventional dosage forms by multiple dosing can produce the desired drug blood level for extended period of time. Frequently however these problems are significant enough to make drug therapy with conventional dosage forms less desirable than sustained drug therapy 1.2.4. Conventional NSAIDs: It is extremely important to obtain an accurate diagnosis before trying to find a cure. Many diseases and conditions share common symptoms: if you treat yourself for the wrong illness or a specific symptom of a complex disease, you may delay legitimate treatment of a serious underlying problem. In other words, the greatest danger in self-treatment may be self-diagnosis. In those patients with osteoarthritis whose symptoms are not relieved by non-pharmacological therapy and ibuprofen and who have no gastrointestinal risk factors, it is appropriate to use conventional NSAIDs, commencing at a low dose and titrating against efficacy. Virtually all currently available conventional NSAIDs have been tested in randomised, placebo-controlled trials in patients with osteoarthritis and rheumatoid arthritis. In these studies, conventional NSAIDs have been shown to be superior to placebo, but there has not been evidence suggesting that one agent is more effective than another. There does, however, appear to be a hierarchy of gastrointestinal risk, with agents such as paracetamol and diclofenac being of the lowest risk and piroxicam and ketoprofen the highest. Those with gastrointestinal risk factors who are unable to take CSIs, NSAIDs could be prescribed, ideally with an agent to reduce the risk of gastrointestinal bleeding. The prostaglandin analogue misoprostol or the proton- pump inhibitor omeprazole have both been shown to reduce the risk of ulcer complications in patients taking conventional NSAIDs. Unfortunately, the Pharmaceutical Benefits Scheme in Australia does not currently support the prophylactic co-prescribing of misoprostol or omeprazole. Conventional doses of H2- receptor antagonists have not been found to protect patients from adverse gastrointestinal events. 1.3.Ibuprofen and NSAIDs: Ibuprofen is in a group of drugs called nonsteroidal anti- inflammatory drugs (NSAIDs). The exact mechanism of action of paracetamol/acetaminophen is uncertain, but it appears to be acting centrally.Ibuprofen as NSAIDs inhibit cyclooxygenase, leading to a decrease in prostaglandin production; this reduces pain and also inflammation (in contrast to paracetamol and the opioids).Ibuprofen has few side effects.NSAIDs may predispose to peptic ulcers, renal failure, allergic reactions, and hearing loss. They may also increase the risk of hemorrhage by affecting platelet function. The use of certain NSAIDs in children under 16 suffering from viral illness may contribute to Reye's syndrome. Ibuprofen is used to reduce fever and treat pain or inflammation caused by many conditions such as headache, toothache, back pain, arthritis, menstrual cramps, or minor injury. Ibuprofen may also be used for other purposes not listed in this medication guide 1.4.Comparison with other NSAIDs: Ibuprofen unlike other common analgesic and antipyretic drug such as aspirin and paracetamol, that is used for the relief of fever and other minor aches and pains. Ibuprofen is also useful in managing more severe pain, allowing lower dosages of additional non-steroidal anti-inflammatory drugs (NSAIDs) or opioid analgesics to be used, thereby minimizing overall side-effects. 1.5. Historical Background of Ibuprofen: When ibuprofen was placed on drugstore shelves in May, 1984, it was the first new over-the-counter (OTC) pain-relief medication to enter the marketplace in a generation. Prior to its introduction, nonprescription pain relief was mainly provided by acetaminophen (introduced in 1955) and aspirin (marketed since 1899). Ibuprofen was developed by the Boots Company, a British drug manufacturer and retailer. Early in the 1960s, researchers at Boots identified carboxylic acid as the agent that gave aspirin its anti-inflammatory property. The Boots group investigated other carboxylic acids; when they found one that was twice as strong as aspirin, they synthesized and tested more than 600 compounds from these acids. The most effective and useful of these was ibuprofen, which Boots began to sell in 1964 in the United Kingdom as the prescription medication Brufen. (Ibuprofen became available OCT in the U.K. in 1983.) Ibuprofen appeared in American pharmacies in 1974 when Boots granted a nonexclusive license to the Upjohn Company, which marketed ibuprofen as the prescription arthritis-relief drug Motrin. This drug soon became one of the most commonly prescribed drugs in the United States. A few years later, Boots began selling its own prescription-form ibuprofen, called Rufen, in the United States. When the United States Food and Drug Administration approved OTC sales of ibuprofen at a lower dosage than in prescription form, two major drug companies immediately geared up for a product-introduction blitz. First, the Whitehall Laboratories division of American Home Products came out with Advil. This was soon followed by Nuprin, which was produced by Upjohn and marketed by Bristol-Meyers. Both operated under licenses from Boots, which held the worldwide patent for ibuprofen until May 1985 and exclusive marketing rights until September 1986. After that date, new manufacturers jumped into the lucrative market with products of their own, including Johnson & Johnson's Medipren, Thompson's Ibuprin, and a number of generic and private-label brands. Upjohn and AHP/Whitehall countered with two new ibuprofen products, Haltran and Trendar, promoted as pain relief for menstrual cramps. Sterling Drugs then introduced its own ibuprofen-based menstrual cramps product, Midol 200. Although ibuprofen, aspirin, and acetaminophen are chemically different, all three give effective relief for minor aches and pains. Ibuprofen seems to cause fewer stomach problems than aspirin. This drug is important because it replaces its more dangerous relative, aspirin. Aspirin causes stomach distress in 2- 10% of users, as well as affecting the blood's ability to clot. Reye's syndrome, another serious side effect of aspirin, affects children
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