Biopharmaceutical Principles of Drug Delivery

Biopharmaceutics can be defined as the study of how the physicochemical properties of drugs, dosage forms and routes of administration affect the rate and extent of drug absorption. The relationship between the drug, its dosage form and the route by which it is administered governs how much of the drug enters the systemic circulation and at what rate. 

For a drug to be effective, enough of it needs to reach its site(s) of action and stay there long enough to be able to exert its pharmacological effect. This is determined by the route of administration, the form in which the drug is administered and the rate at which it is delivered.

Once the drug reaches the blood it partitions between the plasma and the red blood cells, the erythrocytes. Drug in plasma partitions between the plasma proteins (mainly albumin) and the plasma water. It is the free or unbound drug in plasma water, and not the drug bound to the proteins, that passes out of the plasma through the capillary endothelium and to tissues and hence the site(s) of action. Therefore, plasma protein binding is a critical parameter to consider when investigating the therapeutic effect of a drug molecule.

A dynamic equilibrium exists between the concentration of the drug in the blood plasma and the drug at its site(s) of action. This is what is termed distribution, the degree of which will depend largely on the physicochemical properties of the drug, in particular its lipophilicity.

The concentration of the drug in blood plasma depends on numerous factors. These include:

• the amount of an administered dose that is absorbed and reaches the systemic circulation; 
• the extent of distribution of the drug between the systemic circulation and other tissues and fluids (which is usually a rapid and reversible process) and 
• the rate of elimination of the drug from the body.

The drug can either be eliminated unchanged, or be enzymatically  cleaved or biochemically transformed, in which case it is said to have been metabolized. 

The study and characterization of the time course of drug absorption, distribution, metabolism and elimination (ADME) is termed pharmacokinetics. In contrast, pharmacodynamics is the study of the biochemical and physiological effects of the drug on the body.

Many factors have been found to influence the rate and extent of absorption, and hence the time course of a drug in the plasma, and therefore at its site(s) of action. These include:

- the foods eaten by the patient, 

- the effect of the disease state on drug absorption, 

- the age of the patient, 

- the site(s) of absorption of the administered drug, 

- the co-administration of other drugs, 

- the physical and chemical properties of the administered drug, 

-the type of dosage form, 

- the composition and method of manufacture of the dosage form, 

- the size of the dose and the frequency of administration.

Reference: Aulton's Pharmaceutics