**5.1. Simple diffusion**

**4.3. Rectal administration**

**4.4. Parenteral administration**

*4.4.1. Subcutaneous injection*

*4.4.2. Intramuscular injection*

*4.4.3. Intravenous administration*

reasonable efficacy.

rectal route.

478 Drug Discovery

This is the preferred route when the oral route is unsuitable because of nausea or if the drugs have objectionable taste or odor. This route also protects susceptible drugs from the biotransformation reactions in the liver. However, absorption by this route is often ir‐ regular and incomplete. Formulations such as suppositories or enemas are applied via

This mode of administration is also known as injection. It is generally more rapid and enables

This mode of administration is mainly used for non-irritating drugs. It provides even and slows absorption producing sustained drug effects. Vasoconstrictor agents such as epinephrine can

This method of drug delivery ensures rapid absorption of the drug in aqueous solutions. Slow

This route ensures rapid delivery of the desired blood concentration of the drug to be obtained accurately and immediately and is the preferred route of delivery in emergency situations. Irritating drugs are delivered intravenously because the veins have low sensitivity to pain. This mode of delivery is also preferred for drug such as the barbiturates and phenytoin, antiseizure drugs which dissolve only in rather strong alkaline solution and therefore need the blood to buffer the pH of the drug solution for better solubility. Drugs such as ethylene diamine tetra acetic acid (EDTA) for treatment of heavy-metal poisoning are given by intrave‐ nous injection or through an infusion because they are poorly absorbed in the gut. The other advantage of this mode of delivery is the avoidance of the hepatic and pulmonary first-pass effect. Generally, the properties of the drug may determine the route that must be used for

In order for drugs to elicit their pharmacological effects, they have to cross the biological membranes into systemic circulation and reach the site of action. Therefore an insight into the structure and function of the membrane leads to a better understanding of drug absorption.

more accurate dose selection and predictable absorption. Parenteral routes include;

Large volumes of drugs may, however, be painful because of tissue distention.

and even absorption is possible when drugs are suspended in oily vehicles.

**5. Mechanisms of drug absorption across membranes**

be added to the drug solution to decrease the rate of absorption.

This involves is the passage of polar but uncharged substances across water filled chan‐ nels in response to the concentration gradient. Simple diffusion is the mechanism of choice for water soluble drugs and those with low molecular weight such as the an aes‐ thetic nitrous oxide (44kD) and ethanol (46 KDa). The majority of lipid-soluble drugs permeate cell membranes by passive diffusion between the lipid molecules of the mem‐ brane. The permeation rate of a lipid soluble drug depends on the concentration of the drug, its lipid/water partition coefficient concentration of protons and the surface area of the absorbing membrane. The lipid/water partition coefficient of a drug is the principal factor determining its absorption.

The higher the value of lipid/water partition coefficient of a drug, the more rapidly it will be absorbed and vice versa. The chemical force that causes lipid-soluble drugs to move readily across membranes is termed the hydrophobic force since water molecules repels the lipid-soluble drugs. In most cases, drug absorption can be enhanced by ab‐ sorption enhancers, such as fatty acids, phospholipids and muco-adhesive polymers. These compounds disrupt the lipid bilayer making it more permeable and also increase the solubility of insoluble drugs.
