4.4. Specific Systems

Of the four main approaches to controlled release, polymeric devices, drug modification, pumps and site modification, the area that has received most attention is the use of polymers to regulate the delivery profile. In describing the systems, we will go into the greatest detail with these polymeric systems since they have received the lions share of attention.

4.4.1. Reservoir Systems

One of the most widely used polymeric system is called the reservoir system, and it has found commercial success as skin patches. Reservoir systems could also be in the form of microcapsules or hollow fibers. Essentially the drug is retained in a central compartment and surround by a polymeric membrane, through which it must diffuse, and which therefore controls the rate of delivery. Figure 4.4.1 describes the system.

Figure 4.4.1. The reservoir system

The most common polymers that are used are silicone, ethylene vinyl acetate and hydrogels. One disadvantage of these polymers is that if they are implanted in the body, they must be removed once the drug is exhausted. In addition, reservoir devices are not suitable for delivery of high molecular weight drugs, because the drug will not diffuse through the polymer. However, the major disadvantage is that if they contain a potent drug, and the device were to rupture, a potentially fatal dose of drug would be administered.

Drug is released from a reservoir system by first dissolving in the polymer membrane, diffusing across it., and dissolving in the fluid on the other side. The diffusion is down a gradient from the highly concentrated core to the very low concentration of the body. Since body fluid is constantly being exchanged, the conditions which most mimic the in vivo situation are what are called, infinite sink conditions. This means that drug concentration at the body side of the membrane is essentially zero.

Figure 4.4.2. Representation of the concentration gradient across a membrane.

The flux (g/cm2sec), can be described by Fick's first law:

Frequently the drug will preferentially partition into the membrane, in which case the situation is as depicted in Figure 4.4.3.

Figure 4.4.3. Preferential partitioning into a membrane.

In this case flux is modified to include a partition coefficient , K, and can be written as:

Here C is the difference in concentration between the concentrated and dilute sides of the membrane. As before the term DK/l is referred to as the permeability coefficient, which is equal to J/C, which is a straightforward parameter to measure.

If we are dealing with a slab with a surface area A, with a constant concentration of drug in the reservoir, and infinite sink conditions in the body, we can write:

Similar rate equations can be derived for a cylinder and a sphere. For a cylinder of height h and outside and inside radius ro and ri respectively:

For a sphere of outside and inside radius ro and ri respectively:

The rate of release from any of these shapes can be affected if the solute does not get removed from the membrane/body interface rapidly. This can happen if the drug is poorly soluble. This buildup of drug will lower the concentration gradient and the flux will drop. In extreme cases if buildup is so bad that the drug reaches saturation concentration at the membrane surface, then release will stop

Another situation that affects the release rate is the case of a freshly prepared membrane. Just after manufacture the membrane contains no drug, and a steady state situation has not developed. The release at time t during this initial phase can be described by:

On the other hand when a membrane has been stored for a long period of time, drug will accumulate in the membrane, and this will result in a burst of release at the initial time points:

If the membrane dimensions remains the same, i.e. if it does not swell, and if the core concentration of drug remains saturated, and if infinite sink conditions are maintained at the membrane surface, then the steady state rate of drug release will be a function of (and can be controlled by), the area, the diffusion coefficient of the drug, the partition coefficient the concentration gradient and the thickness often membrane. The overall rate will be constant, that is it will be zero order with respect to drug.

It is possible to derive similar equations for various different geometries of reservoir systems. Some common examples are given below.

Equation for a Slab

Equation for a cylinder

Equation for a sphere

Table 4.4.1. gives a list of some of the reservoir devices that are commercially available for drug delivery.

Table 4.4.1. Commercial Pharmaceutical Controlled Release Devices

Product and Manufacturer


Type of Device


Population Council

Subdermal implant to deliver

levonorgestrel for


Reservoir,hollow fiber/silicone

rubber membranes



IUD to deliver progesterone

Delivers 65 µg/day for 1 year

EVA membrane



Ocular insert delivering

pilocarpine for treating

glaucoma. Delivers 20 or

40 µg/h, 7 days

EVA membrane



Transdermal Scopolamine

delivers 10 µg/h for 72 h

for motion sickness.

Microporous membrane



Transdermal Nitroglycerine

delivery for angina

Microporous membrane