Page 185 - Biomedical Engineering and Design Handbook Volume 2, Applications

164 MEDICAL DEVICE DESIGN

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In addition, skin with surface area of 2 m is a commonly used route for drug delivery. Advantages
of the transdermal route include avoidance of first-pass effect, potential of multiday therapy with a
single application, rapid termination of drug effects, and easy identification of medication in an emer-
gency. The limitations are skin irritation and/or sensitization, variation of intra- and interindividual
percutaneous absorption, the limited time that a delivery system can remain affixed, and higher cost. 4
Most of the controlled-release delivery systems available in the market for systemic delivery of
drugs utilize oral, parenteral, and transdermal route for their administration. Advances in biotechnology
produced many gene, peptide, and protein drugs with specific demands on route of delivery. Thus,
other routes such as buccal, nasal, ocular, pulmonary, rectal, and vaginal are gaining more attention.

6.3 PHARMACOLOGICAL AND BIOLOGICAL EFFECTS

It is important to consider the human dimension in the design of the drug delivery systems.
Biological factors, such as age, weight, gender, ethnicity, physiological processes, and disease state,
will change the pharmacokinetics and pharmacodynamics of a drug. For example, dosing newborn
infants requires caution due to their immature hepatic function and higher water content in the body.
Geriatric patients may suffer from reduced sensitivity of certain receptors that may lead to insensi-
tivity to certain drugs. It has been found that different ethnic groups respond to drugs differently.
Diuretics and calcium channel blockers are recommended as the first-line therapy in hypertensive
Black patients, while beta-blockers work better for Caucasian patients. Pathological changes may
influence the distribution and bioavailability of the drug by altering the physiological process.
Decreased kidney and/or liver functions will affect the clearance of many drugs.
In this chapter, the discussion of the design of drug delivery system is based on various approaches:
prodrug approach, diffusion-controlled reservoir and matrix systems, dissolution/coating-controlled sys-
tems, osmotically controlled systems, ion-exchange resin systems, gastroretentive systems, and
approaches for macromolecular drug delivery. The aim of this chapter is to introduce the basic concepts
for the designs of various drug delivery systems. Readers can refer to Refs. 2 to 9 for further details.

6.4 PRODRUG

The molecule with the most potent form does not always have the desired physicochemical proper-
ties needed for drug dissolution and/or absorption. In fact, of all the pharmaceutically active ingre-
dients, 43 percent are sparingly soluble or insoluble in water. In the prodrug approach for drug
delivery, active ingredients are chemically modified by connecting specialized functional groups that
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will be removed in the body after administration releasing the parent molecule. These latent groups
are used in a transient manner to change the properties of the parent drug to achieve a specific func-
tion, for example, alter permeability, solubility, or stability. After the prodrug has achieved its goal,
the functional group is removed in the body (enzymatic cleavage or hydrolysis) and the parent com-
pound is released to elicit its pharmacological action (Fig. 6.2).
The prodrug approach has been used for one or more of the following reasons:
To Change Half-Life. Half-life is defined as time required by the biological system for removing
50 percent of administered drug. Drugs with very short half-life may not be therapeutically beneficial

DRUG
PRO DRUG ACTION
Vs. Biotransformation

PRO DRUG PRO DRUG
Barrier
FIGURE 6.2 Schematic design of prodrug principle.