Page 196 - Biomedical Engineering and Design Handbook Volume 2, Applications

DESIGN OF CONTROLLED-RELEASE DRUG DELIVERY SYSTEMS 175

the administration of a floating device. Supine position of the patient will move the floating device near
to the pyloric sphincter from where it can pass into the intestine. Therefore, in addition to drug and sys-
tem design considerations, the physiological considerations should also be considered when designing
a gastroretentive delivery system.

6.11 DELIVERY OF MACROMOLECULES

The advances in biotechnology have introduced many proteins and other macromolecules that have
potential therapeutic applications. These macromolecules bring new challenges to formulation scien-
tists, since the digestive system is highly effective in metabolizing these molecules, making oral deliv-
ery almost impossible, while parenteral routes are painful and difficult to administer. A potential carrier
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for oral delivery of macromolecules is polymerized liposomes. Liposomes are lipid vesicles that target
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the drug to selected tissues either by passive or active mechanisms. Advantages of liposomes include
increased efficacy and therapeutic index, reduction in toxicity of the encapsulated agent, and increased
stability via encapsulation. One major weakness of liposome is the potential leakage of encapsulated
drugs because of the stability of liposome. Unlike traditional liposomes, the polymerized liposomes are
more rigid due to cross-linking and allow the polymerized liposomes to withstand harsh stomach acids
and phospholipase. This carrier is currently being tested for oral delivery of vaccines.
Pulmonary route is also being utilized as a route for delivery of macromolecules. The lung’s large
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absorptive surface area of around 100 m makes this route a promising alternative route for protein
administration. Drug particle size is a key parameter to pulmonary drug delivery. To reduce the parti-
cle size, a special drying process called glass stabilization technology was developed. By using this
technology, dried powder particles can be designed at an optimum size of 1 to 5 μm for deep lung
delivery. Advantages of powder formulation include higher stability of peptide and protein for longer
shelf-life, lower risk of microbial growth, and higher drug loading compared to liquid formulation. 16
Liquid formulations for accurate and reproducible pulmonary delivery are now made possible by tech-
nology which converts large or small molecules into fine-particle aerosols and deposits them deep into
the lungs. The device has a drug chamber that holds the liquid formulation, and upon activation, the
pressure will drive the liquid through fine pores, creating the microsized mist for pulmonary delivery.
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Transdermal needleless injection devices are another candidate for protein delivery. The device
propels the drug with a supersonic stream of helium gas. When the helium ampule is activated, the
gas stream breaks the membrane which holds the drug. The drug particles are picked up by a stream
of gas and propelled fast enough to penetrate the stratum corneum (the rate-limiting barrier of the
skin). This delivery device is ideal for painless delivery of vaccine through the skin to higher drug
loading. Limitations to this device are the upper threshold of approximately 3 mg and temporary
permeability change of skin at the site of administration. An alternative way to penetrate the skin
barrier has been developed utilizing thin titanium screens with precision microprojections to physically
create pathways through the skin and allow for transportation of macromolecules. Another example
of macromolecular delivery is an implantable osmotic pump designed to deliver protein drugs in a
precise manner for up to 1 year. This implantable device uses osmotic pressure to push the drug for-
mulation out of the device through the delivery orifice.

6.12 CONCLUSION

Controlled-release delivery devices have been developed for almost 40 years. Most of the devices
utilize the fundamental principles of diffusion, dissolution, ion exchange, and osmosis (Table 6.2).
Optimal design of a drug delivery system will require a detailed understanding of release mecha-
nisms, properties of drugs and carrier materials, barrier characteristics, pharmacological effect of
drugs, and pharmacokinetics. With development in the field of biotechnology, there is an increase in
the number of protein and other macromolecular drugs. These drugs introduce new challenges and
opportunities for the design of drug delivery systems.