Polymer membrane reservoir devices

Diffusion-controlled devices may be designed for continuous release and usually use either a matrix or reservoir construction. In matrix systems, the drug is dispersed randomly throughout a polymer, whereas reservoir devices surround the drug with an intact rate-controlling membrane. Regardless of the method of construction, the system must be safe and biocompatible for biological application. 

FIGURE 14 In vitro rate of release of testosterone from a PCL capsule (reservoir device), illustrating rate control by drug dissolution when the polymer membrane thickness is small. (From Ref. 68.)... 

Diffusion systems are characterized by the release rate of a drug being dependent on its diffusion through an inert membrane barrier. Usually this barrier is an insoluble polymer. In general, two types or subclasses of diffusional systems are recognized reservoir devices and matrix devices. These will be considered separately. 

In both cases, drug release is governed by diffusion, i.e. the drug moiety must diffuse through the polymer membrane (for a reservoir device) or the polymeric matrix (for a matrix device), in order to be released. 

The use of rate-limiting membranes to control the movement of dmgs from a reservoir has been referred to above. Implants of silicone rubber or other appropriate polymeric material in which dmg is embedded can be designed by choice of polymer, membrane thickness and porosity, to release dmg at preselected rates. The Progestasert device (Fig. 8.34c) is designed to be implanted into the uterine... 

Nonimmediate- or sustained-release devices can be divided into two categories. The first is a reservoir device whereby the dmg is loaded into the reservoir as either a solid or a liquid. Dmg release occurs by diffusion through either a semipermeable membrane or a small orifice. Lasers are commonly used to generate uniform orifices through which the dmg will diffuse. Osmotic pressure is commonly used to provide the driving force for dmg dispersion. The second is a matrix diffusion device whereby the dmg is dispersed evenly in a solid matrix. Polymers are commonly used as the matrix. Dmg delivery is accomplished by either dissolution of the matrix, with corresponding release of dmg, or diffusion of the dmg from the insoluble matrix. 

Figure 9.2 Reservoir delivery systems based on rate-limiting polymer membranes. Rate-limiting polymer membranes can be used to produce several different types of drug delivery devices including (a) transdermal delivery systems, (b) planar con-trolled-release systems, and (c) cylindrical controlled-release systems.

The cumulative mass of drug released is plotted versus time for planar reservoir devices with a range of physical characteristics, which are determined principally by the diffusion coefficient for the drug in the polymer and the membrane thickness. The cumulative mass released on the y-axis is scaled by Mq = Ac iL and each of the separate curves represents the normalized mass released at a particular value of Dyp/ l (in min" ). If Di p is equal to 1 x 10" cm /s, then these curves correspond to thicknesses (L) of 20, 40, 60, and 120 /xm (from left to right). 

Reservoir Device A device in which the drag to be released is surrounded by an appropriate polymer membrane. 

The most well known commercial reservoir controlled release systems deliver hormones for contraception from hydrophobic polymers. The Norplant subcutaneous device controls the release of levonorgestrel with silicone rubber, and the Progestasert intrauterine device (lUD) releases progesterone from reservoir devices of ethylene vinyl acetate. In the field of insecticides, reservoir dispensers called BioLure were developed to provide zero-order release ofinsect pheromones to disrupt mating (Smith et al, 1983). The dispenser consists of a slab configuration with a rate-controlling membrane, with constant release described by Eq. 1. 

This is contrasted with the reservoir device where a highly concentrated reservoir of drug is enclosed by a thick polymer membrane. As with monolithic devices the release is via diffusion across the polymer membrane, but the drug release kinetics are different for the two types of devices. 

Reservoir devices form an important class of controlled release vehicles. Here the chemical to be released is surrounded by an appropriate polymer membrane. In many instances, the polymer is relatively impermeable to water and release occurs via diffusion of the chemical through the membrane. If the chemical is present as an aqueous solution then the release rate declines with time as its activity within the membrane declines. However, if the chemical exists as a suspension within the reservoir, its activity will remain constant so long as saturation is maintained, thus ensuring a constant release rate. Several commercial devices based on this principle now exist. 

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