FORMULATION

Although a typical tablet may weigh 200–300 mg, it may contain only 1 mg of active material. This poses problems of accurate dispensing and analysis. There must be an even distribution of the active drug in the tablet. It is no use having 49 tablets with no active constituent and 1 tablet containing 50 mg. The diluent may be lactose (milk sugar), dextrose or cellulose. The tablet may be held together by a binding agent such as acacia gum, sodium alginate or gelatin. Sometimes the tablet contains a lubricant such as a vegetable oil, magnesium stearate or polyethylene glycol and a wetting agent such as a detergent to facilitate the adminstration of the tablet. Some forms of starch swell on contact with water and therefore facilitate the disintegration of a tablet and its dissolution in water. The tablet may also contain colouring and flavouring matters. Formulation is an important aspect of medicinal chemistry. An active drug must be given in a form that is acceptable to a patient. The rate at which a substance dissolves is proportional to the surface area of the particle. Small particles dissolve much more quickly than large ones. Different polymorphic crystalline forms of a drug may dissolve at a different rate and hence their overall absorption may be affected. This in turn can affect the biological activity of a drug. It is often the case that a patent may specify a particular polymorphic form of a drug. Sometimes a tablet is coated with an ‘enteric coating’ such as cellulose acetate, which dissolves at a pH greater than 5.8. This prevents the tablet decomposing until after it has left the acidic regions of the stomach. The coating of a tablet may also provide a slow release form of the drug. Some drugs have a rapid onset of action and rapid excretion. Multiple doses over short time intervals may be required in order to maintain an effective concentration in the blood stream and yet avoid high toxic levels. This has been overcome by using a slow-release form of coating. For example, pseudoephedrine dries up the rhinitis in the symptoms of the common cold. However, too much taken at one time could have a serious effect on heart rate. Giving this drug in a slow-release capsule allows the effect on the rhinitis to last for upto 12 h while minimizing the harmful side effect. Liquid formulations present a further series of medicinal chemistry problems. Many organic compounds are poorly soluble in water. Conversion of an acid or an amine to a salt may overcome this. The selection of the correct salt can be a matter of careful research. Many formulations contain alcohol or a syrup to overcome solubility problems. It is important to consider the shelf life of a liquid preparation. In a pharmacy and subsequently in the home, a bottle may be subject to photochemical reactions from sunlight and to autoxidation by air in a warm environment. These factors can contribute to drug stability. Many a medicine cupboard contains old bottles of drugs, which have decomposed or crystallized out. If you open an old bottle of aspirin, it is possible to smell the acetic acid arising from the decomposition of the acetylsalicylic acid. In some instances it is possible that the decomposition products may be toxic.