Osmotic push-pull

Osmotic Pressure Controlled Oral Tablets. Alza Corp. has developed a system that is dependent on osmotic pressure developed within a tablet. The core of the tablet is the water-soluble dmg encapsulated in a hydrophobic, semipermeable membrane. Water enters the tablet through the membrane and dissolves the dmg creating a greater osmotic pressure within the tablet. The dmg solution exits at a zero-order rate through a laser drilled hole in the membrane. Should the dmg itself be unable to provide sufficient osmotic pressure to create the necessary pressure gradient, other water-soluble salts or a layer of polymer can be added to the dmg layer. The polymer swells and pushes the dmg solution through the orifice in what is known as a push-pull system (Fig. 3). The exhausted dmg unit then passes out of the body in fecal matter. 

Fig. 3. (a) Cross section of the push-pull oral osmotic system (OROS), which has an inner flexible partition to segregate the osmotic propellant from the dmg compartment, (b) Push-pull OROS in operation with the propellant imbibing water, increasing in volume, and pushing the dmg out of the device... 

Fig. 8. Example of a Push-Pull osmotic pump where (a) represents the pump before operation, and (b), during operation.

Delivery systems that use a multicompartment core can theoretically deliver drugs of any solubility [48,49], A basic Push-Pull System consists of two layers the Lrst contains the drug, osmotically active hydrophilic polymer(s), and other pharmaceutical excipients the second layer, often called the push layer, contains a hydrophilic expansion polymer, other osmotically active agents, and the excipients, as shown in Figure 22.6. Poorly water-soluble compounds can be delivered using an ORO Push-Pull tlelivery system by incorporating drug as a micronized form, or as a hot-melt material suspended in a polymer matrix. 

The preceding equations apply to Push-Pull osmotic pumps that deliver water-soluble compounds. In that case, both drug and osmotic... 

The invention that positioned osmosis as a major driving force for controlled drug delivery was the elementary osmotic delivery system. ALZA has developed elementary osmotic delivery systems under the name OROS. A successful modification that overcame the disadvantages of the elementary osmotic pump was the Push-Pull osmotic drug delivery system. The following sections are devoted to the principal features of these systems. 

OROS Push-Pull system. After the introduction of commercial products based on EOP technology in the early 1980s, numerous attempts were made to apply the osmotic concept to a broader range of drugs. Since the elementary osmotic pump is limited to the delivery of relatively soluble drugs with solubilities greater than about 2 to 10 wt%, depending on dose, other modifications were necessary to expand the utility of the EOP... 

Push-Pull osmotic delivery system (ALZA Corp.) Multilayered tablet for drugs with low to high solubility... 

This push-pull system has been applied to a system containing a liquid formulation (called L-OROS ). A liquid drug layer and an osmotic engine, or push layer, are encased in a hard gelatin capsule surrounded by a semipermeable membrane. However, there is a barrier layer separating the drug layer from the push layer in order to prevent any interaction between the two. A laser-drilled orifice is set in the top of the drug layer. 

A CR osmotic system based on OROS push-pull technology to deliver drugs to the oral cavity for extended time periods. 

Rgure 8.38 Cross-section of the push-pull osmotic pump for nifedipine. 

FIGURE 22.5 Schematic illustration of an elementary osmotic pump (a) and a push-pull osmotic pump device (b). 

OROS hydromorphone utilizes the patented Push-Pull osmotic pump technology which provides a steady and continuous release of drug over 24 hours, thus providing consistent drug plasma levels and... 

Figure 15.7 Starling principle a summary of forces determining the bulk flow of fluid across the wall of a capillary. Hydrostatic forces include capillary pressure (Pc) and interstitial fluid pressure (PJ. Capillary pressure pushes fluid out of the capillary. Interstitial fluid pressure is negative and acts as a suction pulling fluid out of the capillary. Osmotic forces include plasma colloid osmotic pressure (np) and interstitial fluid colloid osmotic pressure (n,). These forces are caused by proteins that pull fluid toward them. The sum of these four forces results in net filtration of fluid at the arteriolar end of the capillary (where Pc is high) and net reabsorption of fluid at the venular end of the capillary (where Pc is low).

Students often think about osmotic pressure es the pressure pulling into a solution, and hydrostatic pressure as the pressure pushing out Df a solution. Although this is technically Incorrect because pressure is a scalar and lias no direction, thinking about osmotic pressure in this way may give you some intuition about it. 

The hydrostatic pressure in an arteriole is the force that "pushes" fluid out of the capillary and into the interstitial spaces. The plasma protein osmotic pressure, plus the tissue pressure, is the force that "pulls" water from interstitial spaces into the venular side of the capillary. Thus, if the hydrostatic pressure is greater than the osmotic pressure, fluid will leave the circulation if it is less, fluid will enter the circulation. 

---