Evolution of osmotically controlled-release systems
Figure 1: Illustration of the (a) elementary osmotic pump and the (b) push-pull osmotic pump. (FIGURE 1 IS COURTESY OF THE
Osmotically controlled oral drug-delivery systems have come a long way. The first elementary osmotic pump, invented by Theeuwes,
consists of a single compartment containing the drug and an osmotic agent surrounded by a semipermeable membrane (15, 16).
Upon ingestion, water is drawn into the core through the semipermeable membrane to saturate the drug, which is then released
in liquid form at a controlled rate through the orifice(s) (see Figure 1a).
The limitation of the elementary osmotic pump, however, is that it can only deliver water-soluble drugs. The design was further
improved by Cortese and Theeuwes, resulting in the development of the push-pull osmotic pump, which is a bilayer tablet capable
of delivering both highly and poorly soluble drugs (17). The upper layer (i.e., the drug layer, also known as the pull layer)
consists of the drug and an osmotic agent while the lower layer (i.e., the push layer) consists of water-swellable polymers
and osmotic agents (see Figure 1b). Both layers are coated with a semipermeable membrane that regulates water influx into the system. As water enters the tablet,
pressure increases and the polymer swells to push against the drug layer, thereby releasing the drug solution or suspension
through the laser-drilled orifice(s).
Zentner et al. reported on the development of the controlled-porosity osmotic pump in the mid-1980s. The controlled-porosity
osmotic pump does not require a delivery orifice for drug release, hence eliminating the need for complicated laser-drilling
procedures (18, 19). It consists of the drug and an osmotic agent in a tablet core surrounded by a semipermeable coating membrane
containing leachable pore-forming agents, which dissolves upon contact with water, forming pores through which the drug solution
is pumped out. The rate of drug release is dependent on the thickness of the coating membrane, levels of leachable pore-forming
agents, the amount of soluble components incorporated in the coating, drug solubility within the tablet core and the osmotic
pressure differences across the membrane, but unaffected by pH and gastrointestinal motility (20–22).
In the mid-1990s, Herbig et al. described a new type of membrane coating for osmotic drug delivery. The new coating has an
asymmetric structure, similar to asymmetric membranes made for reverse osmosis or ultrafiltration, in that the coating consists
of a porous substrate with a thin outer skin (23). Asymmetric membranes are made from water-insoluble polymers (usually cellulose
derivatives, such as cellulose acetate, ethyl cellulose and cellulose acetate butyrate) and pore-forming agents (e.g., glycerol,
sorbitol, polyethylene glycol, polyglycolic acid and polylactic acid) using a phase-inversion process.
The use of asymmetric membrane coatings in osmotically controlled oral drug-delivery systems has increased in the past decade
because of the advantages it offers. These benefits include: a higher rate of water influx, which facilitates osmotic delivery
of poorly soluble drugs and enables higher release rates of such drugs; more controlled-release of freely soluble drugs; pH-independent
release and minimized exposure to the gastrointestinal tract, which results in reduced gastric irritation and degradation
of drugs (23–25).
Water permeability of the coating can be adjusted by controlling the membrane structure, thereby allowing control of release
kinetics without altering the coating materials used or significantly varying the coating thickness. The porosity of the membrane
can also be controlled to minimize the lag time that occurs before drug delivery begins (23).
Asymmetric membrane coatings can be applied on pharmaceutical tablets and capsules (23, 26, 27). The basic design of an asymmetric
membrane capsule is similar to a hard-gelatin capsule, except that the shell contains pore-forming water-soluble additives,
which dissolve after coming in contact with water, resulting in an in situ formation of a microporous structure (28, 29). A delivery orifice is, therefore, not required due to the in situ pore formation of the asymmetric membrane.