Absorption of drugs

Several factors can affect the absorption of a drug into the body. These include:

• physicochemical properties (e.g. solubility)
• drug formulation (e.g. tablets, capsules, solutions)
• the route of administration (e.g. oral, buccal, sublingual, rectal, parenteral, topical, or inhaled)
• the rate of gastric emptying

The main pharmacokinetic parameters for absorption include:

• Absorption rate constant: absorption rate / amount of drug remaining to be absorbed
• Bioavailability: amount of drug absorbed / drug dose

A drug must be solubilized in order to cross the semipermeable cell membranes to reach the systemic circulation. These biological barriers exist to selectively allow or inhibit the passage of native and foreign particles through them.

Passive diffusion involves the crossing of a pharmaceutical substance across a cell membrane from an area of high drug concentration, such as  in the gastrointestinal tract,  to an area of low drug concentration, such as in  the blood.

This is a passive process that does not require energy, and the rate of diffusion is directly proportional to the concentration gradient. Other factors influencing passive diffusion include:

• the physicochemical properties of the drug, such as its:
  • lipid solubility
  • molecular size
  • degree of ionization
• the absorptive surface area available to the drug.

In general, lipid-soluble drugs, and drugs composed of smaller molecules, cross the cell membrane more easily and are more likely to be absorbed by passive diffusion.

As most drugs are weak acids or bases, they exist in the form of an equilibrium between the ionized and un-ionized form in an aqueous environment, such as the gastrointestinal tract. The un-ionized form usually diffuses across the cell membrane more readily as it is more lipophilic. The ionized form, on the other hand, exhibits high electrical resistance and is less likely to diffuse across the membrane. The ratio of the un-ionized form depends on the environmental pH and the acid dissociation constant (pKa).