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Negligible release

Time

Figure 11 Pulsatile drug-release patterns: negligible release at early time points, followed by rapid and complete release after a predetermined lag phase. Exemplarily, a polymer-coated pellet is illustrated: The intact macromolecular membrane effectively hinders drug release until the steadily increasing hydrostatic pressure within the pellet core (caused by the influx of water) induces crack formation, resulting in rapid drug release through water-filled pores/channels.

Rapid and complete release

Negligible release

Time

Figure 11 Pulsatile drug-release patterns: negligible release at early time points, followed by rapid and complete release after a predetermined lag phase. Exemplarily, a polymer-coated pellet is illustrated: The intact macromolecular membrane effectively hinders drug release until the steadily increasing hydrostatic pressure within the pellet core (caused by the influx of water) induces crack formation, resulting in rapid drug release through water-filled pores/channels.

Pulsatile drag-release patterns (negligible drag release at early time points combined with rapid and complete drag release after a predetermined lag phase) can, for instance, be provided with drag-loaded pellets, which are coated with a polymeric film that is impermeable for the drag as long as the film is intact. The principle of this type of approach is illustrated in Figure 11. Upon contact with aqueous media, water penetrates into the system, resulting in a steadily increasing hydrostatic pressure, which acts against the film coating. As soon as this pressure exceeds the mechanical stability of the polymeric membrane, crack formation is induced in the latter and drag release occurs through water-filled pores/channels.

Promising microchip-based, time-controlled drag delivery systems have been proposed by Langer and coworkers (69-71): Tiny reservoirs on a microchip are loaded with one or more drags using, for example, inkjet printing techniques. The drag can be in the solid, liquid, or semisolid state. The reservoirs can, for instance, be sealed with thin gold layers (e.g., 50 |im x 50 |im and 0.3 |im in thickness), which serve as anodes. The microchip also contains a cathode. When applying a potential of +1.04 V, the gold membranes electrochemically dissolve and the drag is released. One of the fundamental advantages of this novel type of time-controlled drug delivery systems is the considerable number of drag reservoirs that can be located on one single microchip and the fact that each reservoir can be activated individually. Thus, virtually any type of drag-release patterns with one or multiple drugs can be provided. For more details, the reader is referred to chapter 12 of this volume ("Dosage Forms for Personalized Medicine: From the Simple to the Complex").

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