Passive diffusion is a random movement of drug molecules from an area of higher concentration to an area of lower concentration. When a drug is injected into the body, it passively diffuses from the injection site to areas of lower concentration, eventually reaching a blood capillary and entering the systemic circulation. In this process no cellular energy is expended and no transport carrier protein is involved. Hence the term passive diffusion is used.
Many drugs pass through the biological membranes such as cell membranes by passive diffusion. For a drug to passively diffuse from one side to another, the drug must dissolve in the membrane that is composed of phospholipids, and diffuse down the concentration gradient.
Passive diffusion continues until enough molecules have passed from an area of higher concentration to an area of lower concentration till equilibrium is attained on either side of the membrane. Drug molecules continue to move, however, such that an equal number move into and out of both the areas.
Passive diffusion is the most important mechanism for majority of drugs. Lipid soluble drugs diffuse by dissolving in the lipoidal matrix of the membrane. The rate of transport being proportional to lipid: water partition coefficient of the drug.
Passive diffusion is mostly dependent upon:
Concentration gradient (greater is the difference in the concentration of the drug on the two sides of the membrane, faster is its diffusion)
Drug molecular size (smaller molecules move more rapidly than bigger molecules)
Lipophilic nature of the molecule (higher the lipid solubility higher is the diffusion)
Temperature (lower the temperature, slower the diffusion)
Thickness of the membrane (the thicker the membrane the slower the diffusion)
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