Osmotically active agent

Hypertonic hyponatremia is usually associated with significant hyperglycemia. Glucose is an osmotically active agent that leads to an increase in TBW with little change in total body sodium. For every 60 mg/dL (3.33 mmol/L) increase in serum glucose above 200 mg/dL (11.1 mmol/L), the sodium is expected to decrease by approximately 1 mEq/L (1 mmol/L). Appropriate treatment of the hyperglycemia will return the serum sodium to normal.15... 

The proximal tubule and descending limb of Henle s loop are freely permeable to water (Table 15-1). Any osmotically active agent that is filtered by the glomerulus but not reabsorbed causes water to be retained in these segments and promotes a water diuresis. Such agents can be used to reduce intracranial pressure and to promote prompt removal of renal toxins. The prototypic osmotic diuretic is mannitol. 

High doses of osmotically active agents produce prompt bowel evacuation (purgation) within 1-3 hours. The rapid movement of water into the distal small bowel and colon leads to a high volume of liquid stool followed by rapid relief of constipation. The most commonly used purgatives are magnesium citrate and sodium phosphate. 

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. 

Osmosis a semi-permeable membrane containing holes of a certain diameter surrounds the active substance and an osmotic active agent. In contact with water, the osmotic active agent attracts water, which results in release of the content through the holes. 

Vargas G, Chan KF, Thomsen SL, Welch AJ. Use of osmotically active agents to alter optical properties of tissue effects on the detected fluorescence signal measured through skin. Lasers Surg Med 2001 29(3) 213-220. 

Flanner, H.H., etal. System for osmotic delivery of pharmaceutical active agents, US Patent 6838093,... 

The development of low osmolar non-ionic X-ray contrast agents has resulted in a distinct reduction in the toxicity and the observed side-effects in patients. However, as already mentioned the osmotic activity of MRI contrast agents is less important in view of the smaller injection volumes which are used. All the formulations of extracellular gadolinium chelates are hypertonic when compared with blood. But the overall increase in osmolality after injection of even 0.3 mmol/kg body weight is insignificant. Osmololatiy-induced adverse reactions have been observed rarely not only because of the relatively small injection volumes but also because of the rapid dilution of the injected agent in the blood. 

Recently, osmotic concepts were extended to address delivery of drugs of different physical states. These osmotic systems were uniquely designed to deliver liquid active agents.18 20... 

In one design, the active agent is enclosed in a capsule consisting of a cap, and the body is placed inside the compartment of the main body. Within the inner capsule, distant from the orifice, an osmotic composition resides that acts as a push layer. Alternatively, the drug can be enclosed in a one-piece capsule coated with a semipermeable membrane or placed in a thermoplastic polymer compartment19 (Fig. 7.4). In this type of system, the drug and osmotic layers are not separated. 

A multireservoir osmotic system is described in which the drug is more protected from the influx of water than in the previously described delivery system. The design consists of a central reservoir, formed from a water-impermeable layer containing a liquid active agent and osmotic agent separated by a barrier layer (Fig. 7.6). The barrier layer prevents mixing of the layer contents and minimizes the residual amount of the active agent after the expandable osmotic composition has ceased its expansion. The layer also provides uniform pressure transfer from the... 

Figure 7.6 Design of an osmotic device for a liquid active agent with a water-impermeable coat. (Adapted from Dong.20)...

Figure 7.8 Osmotic delivery system for delivery of a liquid active agent.

Elementary osmotic pump (ALZA Corp.) Once-daily osmotic tablet with solid active agent... 

Higuchi, T., and Theeuwes, F Osmotic dispenser with means for dispensing active agent responsive to osmotic gradient, U.S. Patent 3,995,631, 1976. 

Theeuwes, F, and Damani, N. C. Osmotically driven active agent dispenser, U.S. Patent 4,016,880, 1977. 

The osmotic pressure of the saturated salt solution is high, on the order of tens of atmospheres, and the small pressure required to pump the suspension of active agent is insignificant in comparison. Therefore, the rate of water permeation across the semipermeable membrane remains constant as long as sufficient solid salt is present in the salt chamber to maintain a saturated solution and hence a constant osmotic pressure driving force. 

Figure 12.17 The Higuchi-Leeper osmotic pump design [28]. This device has no water chamber and can be stored in a sealed foil pouch indefinitely. However, once removed from the pouch and placed in an aqueous environment, for example, by an animal swallowing the device, the pumping action begins. The active agent is pumped at a constant rate according to Equation (12.14)...

The physical properties of surface active agents differ from those of smaller or nonamphipathic molecules in one major aspect, namely, the abrupt changes in their properties above a critical concentration. This is illustrated in Fig. 1, in which a number of physical properties (surface tension, osmotic pressure, turbidity, solubilization, magnetic resonance, conductivity, and self-diffusion) are plotted as a function of concentration. All these properties (interfacial and bulk) show an abrupt change at a particular concentration, which is consistent with the fact that above this concentration, surface active ions or molecules in solution associate to form larger units. These association units are called micelles and the concentration at which this association phenomenon occurs is known as the critical micelle concentration (cmc). 

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