Page 182 - Biomedical Engineering and Design Handbook Volume 2, Applications

CHAPTER 6

DESIGN OF

CONTROLLED-RELEASE
DRUG DELIVERY SYSTEMS

Steve I. Shen, Shilditya Bhattacharya, Bhaskara R. Jasti,
and Xiaoling Li
Thomas J. Long School of Pharmacy and Health Science,
University of the Pacific, Stockton, California,

6.1 PHYSICOCHEMICAL PROPERTIES OF 6.7 BIODEGRADABLE/ERODIBLE DELIVERY
DRUG 163 SYSTEMS 171
6.2 ROUTES OF DRUG 6.8 OSMOTIC PUMP 171
ADMINISTRATION 163 6.9 ION-EXCHANGE RESINS 173
6.3 PHARMACOLOGICAL AND BIOLOGICAL 6.10 GASTRORETENTIVE DELIVERY
EFFECTS 164 SYSTEMS 174
6.4 PRODRUG 164 6.11 DELIVERY OF MACROMOLECULES 175
6.5 DIFFUSION-CONTROLLED DELIVERY 6.12 CONCLUSION 175
SYSTEMS 165 REFERENCES 178
6.6 DISSOLUTION/COATING-CONTROLLED
DELIVERY SYSTEMS 170

With the advances in science and technology, many new chemical molecules are being created and
tested for therapeutic uses in a much faster pace. The U.S. Food and Drug Administration (FDA)
approved 22 to 53 new molecular entities each year between 1993 and 2006 and slowly decreased to
1
17 in 2007, the lowest in about 24 years. A major problem is the translation of in vitro activity of
new molecules to efficacy in the humans. Creation of these drug molecules is only part of the drug
product development. Every drug molecule needs a delivery system to carry the drug to the site of
action upon administration to the patient. Delivery of the drugs can be achieved using various types
of dosage forms, including tablets, capsules, creams, ointments, liquids, aerosols, injections, and
suppositories. Most of these conventional drug delivery systems are known to provide immediate
release of the drug with little or no control over delivery rate. To achieve and maintain therapeuti-
cally effective plasma concentrations, several doses are needed daily, which may cause significant
fluctuations in plasma levels (Fig. 6.1). Because of these fluctuations in drug plasma levels, the drug
level could fall below the minimum effective concentration (MEC) or exceed the minimum toxic
concentration (MTC). Such fluctuations result in unwanted side effects or lack of intended thera-
peutic benefit to the patient.

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