4.4.2. Matrix Systems

4.4.2.1. Description

Matrix systems consist of a polymer throughout which drug is dispersed. They are easy to make. Any leaks in the system do not create severe problems, as would leakage from a ruptured reservoir, and they can be made to release high molecular weight drugs. The main disadvantage of a matrix system is that is must be removed from the body after the drug has been released.

Figure 4.4.4. Matrix System (after Langer)

4.4.2.2. Modeling Matrix Systems

For modeling purposes four cases are considered. The drug can be either dissolved or dispersed in the polymer, and it can travel out of the device by either diffusion through the polymer, or diffusion through channels. The modeling in each case is somewhat different. In the case of dissolved drug diffusing through the polymer two time periods are considered an early and a late time. In the early time approximation (which usually involves about 60% of release) release is inversely proportional to the square route of time:

Dissolved drug, diffusion through polymer

Early time approximation:

For the late time approximation the equation is as follows

Matrix devices can be made by loading drug into a polymer mixture, physical blending followed by compression or injection molding, extrusion, calendering or solvent casting. In this case drug is dispersed in the polymer, and if it leaves the polymer by diffusion through the polymer, then the model for release becomes:

Dispersed drug, diffusion through polymer

where A is the exposed area of the device
D is the diffusion coefficient of drug in the polymer
Cs is the solution solubility of the drug in the matrix
CL is the total loading of drug in the matrix

This assumes that CL>>>CS. The device maintains a t dependency until the active agent remaining in the device falls below saturation levels. This is a well known relationship known as the Higuchi equation after the scientist who first published this modeling in the Journal of Pharmaceutical Sciences volume 50 p 874-875 in 1961. If a device is following this type of release kinetics a plot of cumulative release against the square root of time will give a straight line.

4.4.2.3. Bioerodible systems

A specific type of matrix system is one in which the polymer is broken down by the body. This breakdown can be via hydrolysis or it can be enzymatic. They are called bioerodible systems, and they have all the advantages of matrix systems, and in addition they do not require removal from the body when release is completed.

Figure 4.4.5. Bioerodible polymeric system

If the method of degradation is by surface erosion, that is similar to peeling off the skins of an onion, then release can be shown to be zero order if the surface area does not change substantially with time. However if, as often happens with hydrophilic polymers, erosion takes place by solvent infiltrating the polymer and causing chunks of polymer to break off, similar to the weathering of rock seen in the Grand Canyon, then release can be in bursts and it can be hard to control. Some of the most widely studied polymer are those used as biodegradable sutures in surgery. These polymers, known as poly lactides and poly glycolides, have been passed for us in humans by the FDA, but they have the disadvantage of eroding by bulk erosion. Poly anhydrides and polyorthoesters can be made to erode by surface erosion. In all these cases care has to be taken to ensure that the breakdown products of the polymer are non toxic, and that they do not interact with the drug.