Rigid, semipermeable membrane Flexible, impermeable membrane

Hydrostatic pressure Osmotically active excipient

Figure 5 Schematic presentation of osmotic-controlled drug delivery systems: (A) one-chamber device; (B) two-chamber device. The osmotically driven influx of water creates considerable hydrostatic pressure within the system, which pushes the drug out into the bulk fluid.

two-chamber device. Both are surrounded by a rigid, semipermeable film coating, which is permeable for water, but not for the drug or excipients. Often, cellulose acetate is used for this purpose. Once the system comes into contact with aqueous body fluids, water penetrates into the device.

In the case of a one-chamber device (Fig. 5A), the water influx is driven by the difference in osmolality of the surrounding bulk fluid and of the drug (and potentially excipient) solution inside the system. The generated hydrostatic pressure pushes the drug solution or suspension out of the dosage form, through one or more holes/orifices in the film coating. As the resulting drug-release rate strongly depends on the diameter of this/these hole(s), the latter(s) is/are often prepared with a laser. Importantly, the semipermeable membrane is rigid, so that the developed hydrostatic pressure fully serves to push out the drug and not to extend the systems' dimensions. If the aqueous solubility of the drug is insufficient to create the required osmotic pressure difference "inside-outside" to achieve the desired drug-release rate, freely water-soluble excipients might be added. The resulting drug-release rate from this type of dosage forms is constant (zero-order kinetics) as long as (i) the drug concentration inside the system is constant (e.g., saturated solution) and (»') the osmotic pressure difference inside-outside is constant (e.g., saturated drug solution inside versus perfect sink outside).

In the case of a two-chamber device (Fig. 5B), the rigid semipermeable membrane surrounds two compartments: one filled with the drug (and eventually excipients) and the other filled with a freely water-soluble excipient, creating significant osmotic pressure upon contact with aqueous media. These two compartments are separated by an impermeable, flexible membrane. The water influx into this type of dosage forms is mainly driven by the osmotically active excipient located in the second chamber. The hydrostatic pressure that is created upon water penetration deforms the flexible, impermeable membrane and, thus, pushes the drug solution or suspension located in the other chamber out of device through the orifice(s) of this chamber. The resulting drug-release rate can be adjusted via the diameter of the hole(s) and the osmotic activity of the excipients (and drug). Again, zero-order release kinetics can be provided as long as the driving forces are constant.


Most degradable/erodible-controlled drug delivery systems are based on polymeric matrix formers. In the case of parenteral administration, they provide the major advantage to avoid the removal of empty remnants upon drug exhaust. Unfortunately, different definitions of the terms erosion and degradation are used in the literature (38). In this chapter, the term polymer degradation is understood as the chain scission process by which macromolecules are cleaved into shorter-chain molecules and finally oligomers and monomers. The term erosion is understood as the process of material loss from the polymer bulk. Such materials can include monomers, oligomers, parts of the polymer backbone, or even parts of the polymer bulk.

Depending on the relative velocities of water penetration into the drug delivery system and polymer chain cleavage, two erosion mechanisms can be distinguished: surface (heterogeneous) and bulk (homogeneous erosion) (39-41). The basic principles of these two mechanisms are illustrated in Figure 6. Exemplarily, schematic cross sections through erodible, cylindrical implants are shown. Before exposure to the release medium (t = 0) (schemes on the left-hand side), the drug is homogeneously distributed within the devices in the form of dissolved (individualized) molecules and undissolved drug excess (e.g., crystals and/or amorphous aggregates), represented by the stars and black circles, respectively. In the case of surface-eroding drug delivery systems (Fig. 6, top row), the rate at which the polymer chains are cleaved is much higher than the rate at which water penetrates into the device. Thus, polymer degradation is mainly restricted to the surface-near regions of the systems. Consequently, the device shrinks with time and the drug is released by the disappearance of the surrounding polymer matrix. The inner structure (e. g., porosity, relative drug content, and distribution) remains about unaltered. In contrast, the water-penetration rate is much greater than the polymer chain-cleavage rate in the case of ¿«/^-eroding drug delivery systems (Fig. 6, bottom row). Thus, the entire device is rapidly wetted upon contact with aqueous media and polymer chain cleavage occurs throughout the system. Due to the presence of water, the drug becomes mobile and diffuses out of the device. In case of initial drug excess, released drug molecules are replaced by the (partial) dissolution of drug crystals/amorphous aggregates. Importantly, the device dimensions remain nearly constant, whereas the inner system structure significantly changes: the porosity increases and the drug concentration decreases. With decreasing average polymer molecular weight, the mobility of the macromolecules increases and, thus, also the drug mobility.

Surface erosion

Bulk erosion

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