A faster onset of action is the key requirement for drugs that are used to manage pain. Generally, medications for pain relief are available in the form of oral dosage forms, and most commonly as tablets. The ultimate goal of a tablet is to serve as a carrier for a drug to reach the blood stream for distribution to its site of action. After oral ingestion, the drug contained within a tablet reaches the bloodstream in a series of steps. First, the tablet disintegrates in the gastrointestinal (GI) tract into fine particles under the influence of the digestive juice. Then, the drug gets dissolved in the GI fluids. Once the drug is present in the GI fluid in the form of a solution, it has the potential to be absorbed. Absorption occurs across the GI membrane by different mechanisms, chiefly by passive diffusion. Among these many steps, the slowest step that controls the overall rate and extent of absorption of intact drug in the systemic circulation is called the rate limiting step. This rate-limiting step may vary from drug to drug. Thus, for a drug that has a very poor aqueous solubility, the rate at which the drug dissolves in the GI fluid is often the slowest step and therefore exhibits a rate-limiting effect on the drug bioavailability. Improvement in the solubility characteristics of such a drug brings about faster solubility in the GI fluid and hence faster absorption and ultimately faster onset of action.
Non-steroidal anti-inflammatory drugs (NSAIDS) remain among the most widely prescribed drugs worldwide. NSAIDS such as aspirin exerts their actions primarily by inhibiting the production of prostaglandins (PGs). Cyclooxygenase (COX), the key enzyme catalyzing the biosynthesis of PGs, was purified in 1976 and cloned in 1988.
A second COX gene was discovered in 1991. It is now known that the two genes express two similar but distinct isoforms of the enzyme - COX-1 and COX-2. The two isoforms have similar primary protein structure and catalyze essentially the same reaction.