4.4.4. Solvent Control

4.4.4.1. Swelling Controlled Systems

One way to control release of drug that is dispersed in a polymer, is to use a polymer that is normally glassy, but when solvent penetrates the matrix swelling takes place and the polymer chains become relaxed and allow the drug to diffuse out. As the solvent front advances, the area that is penetrated swells, and the glassy core area begins to shrink.

Figure 4.4.7. Swelling controlled system

Some of the advantages of these systems include the fact that the releases is a function of the polymer swelling, not of the particular drug, so that one can be used for different drugs without the need to reformulate and as a matrix system, there is no potential for catastrophic rupture with release of large quantities of drug. Also there is no burst effect. However, the number of available polymers is not large, and although for linear polymers dissolution follows the swelling process, cross linked or partly crystalline matrixes can give problems with areas that do not swell, and the resulting introduction of mechanical weakness.

4.4.4.2. Osmotic control

4.4.4.2.1. Description

Another use of solvent to control drug release involves the use of an osmotic core surrounding a flexible reservoir that contains a solution of drug. If the core is itself surrounded with a semipermeable membrane, and if the drug chamber has access to the outside via a small laser-drilled orifice, drug solution will be squeezed out when water enters through the semipermeable membrane, is imbibed by the osmotic core and the core swells.

Figure 4.4.7. Schematic of an osmotic device

The advantages of these systems include the fact that osmosis is a constant driving force which results in zero order release which is independent of the environment; they can be designed to deliver any solution, including solutions of macromolecules such as proteins; and the rate can be designed to be much higher than that with diffusion alone. The best method of achieving zero order release is in the pump type of arrangement described above, although it is also possible to has a system where drug is dispersed in a polymer, together with an osmotic agent, and the water that enters forms pores in the polymer, through which drug is released. These systems tend not to be zero order. Several different patented designs have been developed by the pharmaceutical industry, some for patient use, and others for use in research.

4.4.4.2.2. Modeling of Osmotic Systems

Osmotic systems are modeled by considering the osmotic driving force developed by different substances. Table 4.4.2. lists the osmotic pressure of saturated solutions of some common examples.

Table 4.4.2. Osmotic Pressure of saturated solutions
Compound

Pressure (ATM)

Sodium chloride

356

Fructose

355

Sucrose

150

Potassium sulfate

28

 

Osmotic pressure , is related to concentration (N moles per volume V or N/V) by:

The rate of change of the volume V with time t is related to the area A, the thickness and the difference between the osmotic pressure and the hydrostatic pressure by:

For a large orifice >>> P

To find the amount released with time: