Matrix devices

Passive transdermal dehvery systems on the market tend to be either matrix or membrane controUed. In matrix devices, the stmctural and molecular characteristics of the dmg-polymer matrix determine dmg release. Examples of polymer matrix-controUed diffusional systems for angina prophylaxis include Nitro-Dur and Nitrodisc, which provide transdermal dehvery of nitroglycerin [55-63-0], and Erandol, a tape that releases isosorbide dinitrate [87-33-2]. Matrix diffusional systems have been used for dehvering dmgs with a wide therapeutic index. 

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. 

Brains are rapidly dissected and sectioned by means of a brain matrix device and placed in a pre-ordered position on a Petri dish cooled on ice. 

The kinetics of drug release from matrix devices containing uniformly dissolved or dispersed drug are well documented. In a flat sheet geometry, where the surface area is relatively constant,... 

FIGURE 6.21 Release of tetracycline from trilaminate membrane-matrix devices. [Graph reconstructed from data by Olanoff et al., J. Pharm. Sci., 68, 1147 (1979).]... 

The main use of PVC is for intravenous bags. However, PVC has been used in the controlled release of volatile insecticides, herbicides, pheromones, and perfumes by diffusion through a PVC membrane of multilaminated stripes. A monolithic matrix device of PVC can be prepared by mixing PVC particles with a suitable plasticizer and an active agent, followed by heating of the mixture in a mold. A solid PVC matrix is obtained from the subsequent cooling. 

Table 3.1 Examples of commercial diffusion-controlled reservoir and matrix devices...

Matrix devices Parenteral Compudose cattle growth implant... 

Outline the differences between a reservoir device and a matrix device. 

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. 

Dissolved the drag is soluble in the polymer matrix. A dissolved matrix device (also known as a monolithic solution) appears at a low payload. 

FIGURE 6 Cross-sectional view of severalTDSs (a) poly(sebacic anhydride) (PSA) matrix device (b) membrane-moderated TDS (c) adhesive-controlled TDS (d) microreservoir-type TDS (e) matrix dispersion-type TDS. 

Similarly, McGinnity has shown that incorporation of hygroscopic carriers such as sodium alginate into silicone rubber based matrix devices greatly inaeased the rate of morphine sulfate release and changed its temporal character to approximate more nearly a zero-order pattern. It was noted that inclusion of a carrier caused the device to swell considerably because of water imbibition and no doubt a complex series of events account for the effect on release rate. 

The diffusion coefficients and translational movements of proteins are important in considering the release of proteins from hydrogel matrix devices and other delivery vehicles, and in membrane transport, as far as this can be considered to be a passive diffusion process. Changes in shape during membrane transport in a lipid environment may also have to be considered. Table 11.6 gives some values of diffusion coefficient of a number of therapeutic peptides and proteins. 

For matrix devices the release rate is dependent on the rate of dmg diffusion through the matrix. The amount of dmg released can be expressed by Elqn (6.2),... 

A different strategy for controlled release is based on polymer permeability other than degradation. The active reagent may be encapsulated within a polymeric membrane or in a strip, as shown in Figure 5.53. Ideally the reagent is contained in the reservoir as a saturated solution with excess in suspension. This allows diffusion through the membrane at constant rate without loss of activity. Alternatively, the reagent may be dispersed in a polymer matrix and released to the environment by diffusion or extraction. A variety of membrane and matrix devices are commercially available [99]. Pheromone release strips for insect control and household fly and cockroach strips for release of insecticide are also in commercial use. 

The typical release profiles shown in Figure 32.4 for reservoir and matrix delivery systems may present variations a burst effect due to the presence of some core material too close to the external device surface for matrix devices, or a delayed time to start diffusion due to the diffusion of the core through the encapsulating layer of the reservoir device. Also, the physical state of the core material (dissolved or dispersed) defines the release kinetics. For example, a reservoir system in which the active core is not dissolved results in zero-order kinetics (constant flow), whereas it results in first-order kinetics (exponentially decreasing flow) if the core is dissolved in the encapsulated material. 

Another configuration of diffusion-controlled systems includes matrix devices, which are common because of ease of fabrication. Diffusion control involves dispersion of drug in either a water-insoluble or a hydrophilic polymer. For instance, bupropion hydrochloride (Zyban , GlaxoSmithKline) is formulated using carnuba wax and hydroxypropylmethylcellulose. ... 

S. Lu, W.F. Ramirez, and K.S. Anseth. Modeling and optimization of drug release from laminated polymer matrix devices. AIChE J., 44(7) 1689-1696, 1998. 

---