Page 192 - Biomedical Engineering and Design Handbook Volume 2, Applications

DESIGN OF CONTROLLED-RELEASE DRUG DELIVERY SYSTEMS 171

become available for absorption. Release of drug at a predetermined time is accomplished by con-
trolling the thickness of coating. In Spansule® systems, drug molecules are enclosed in beads of
varying thickness to control the time and amount of drug release. The encapsulated particles with
thin coatings will dissolve and release the drug first while a thicker coating will take longer to dis-
solve and will release the drug at later time. Coating-controlled delivery systems can also be
designed to prevent the degradation of the drug in the acidic environment of the stomach, which can
reach as low as pH 1.0. Such systems are generally referred to as enteric-coated systems. In addi-
tion, enteric coating also protects stomach from ulceration caused by drug agents. Release of the
drug from coating-controlled delivery systems may depend upon the polymer used. A combination
of diffusion and dissolution mechanisms may be required to define the drug release from such
systems.

6.7 BIODEGRADABLE/ERODIBLE DELIVERY SYSTEMS

Biologically degradable systems contain polymers that degrade into smaller fragments inside the
body to release the drug in a controlled manner. Zero-order release can be achieved in these systems
as long as the surface area or activity of the labile linkage between the drug and polymeric backbone
are kept constant during drug release. Another advantage of biodegradable systems is that, when for-
mulated for depot injection, surgical removal can be avoided. These new delivery systems can pro-
tect and stabilize bioactive agents, enable long-term administration, and have potential for delivery
of macromolecules.
A summary of different matrix and coating-controlled release mechanisms is illustrated in Fig. 6.4.

6.8 OSMOTIC PUMP

This type of delivery device has a semipermeable membrane that allows controlled amount of
11
water to diffuse into the core of the device filled with a hydrophilic component. A water-sensitive
component in the core can either dissolve or expand to create osmotic pressure and push the drug
out of device through a small delivery orifice which is drilled to a diameter that correlates to a spe-
cific rate. In an elementary osmotic pump, the drug molecule is mixed with osmotic agent in the
core of the device (Fig. 6.5). For drugs that are highly or poorly water-soluble, a two-compartment
push-pull bilayer system has been developed, in which drug core is separated from the push com-
partment (Fig. 6.5). The main advantage of osmotic pump system is that constant release rate can
be achieved since it relies simply on the passage of water into the system and the human body is
made up of 70 percent water. The release rate of the device can be modified by changing the
amount of osmotic agent, surface area and thickness of semipermeable membrane, and/or the size
of the hole.
The rate of water diffusing into osmotic device is expressed as 12

dV ⎛ AK ⎞
= (Δπ − Δ P) (6.17)
dt ⎝ h ⎠

where dV/dt = change of volume over change in time
A = area
K = permeability
h = thickness of membrane
Δπ = difference in osmotic pressure between drug device and release environment
ΔP = difference in hydrostatic pressure