Osmotic system

In these systems, osmotic pressure provides the driving force to generate controlled release of drug. Consider a semipermeable membrane that is permeable to water, but not to drug. A tablet containing a core of drug surrounded by such a membrane is shown in Fig. 9. When this device is exposed to water or any body fluid, water will flow into the tablet owing to the osmotic pressure difference. The rate of flow, dV/dt, of water into the device can be represented as... 

In some CDD systems, osmotic pressure acts as the driving force to generate a constant release of drug. The advantage of such a system is that it requires only osmotic pressure to be effective and is essentially independent of the environment (13,15). 

In dilute aqueous solutions, surfactants have normal electrolyte or solute characteristics and are formed at the interface. As the surfactant concentration increases beyond the well-defined concentrations (i.e., critical micelle concentration, c.m.c.), the surfactant molecules become more organized aggregates and form micelles. At the c.m.c., the physicochemical characteristics of the system (osmotic pressure, turbidity, surface tension, and electrical conductivity) are suddenly changed, as shown in Figure 4.19. 

Experimentally, the fraction of free counterions in salt-free polyelectrolyte solutions is believed to give the main contribution to the system osmotic pressure. In the framework of the two-state models, the osmotic pressure is equal to the osmotic pressure of the free counterions. The more accurate analysis of the counterion effect on the solution osmotic pressure can be done in the framework of the Poisson-Boltzmann approach and its two-zone model simplification. In order to obtain an expression for the osmotic pressure in the framework of the two-zone model, one has to know the counterion concentration at the outer boundary of the spherical region. This requires knowledge of the electrostatic potential within the spherical zone. However, one can avoid solving the nonlinear Poisson-Boltzmann equation and use the relation between the local pressure P(r) and the electric field (r). To obtain this relation, one has to combine the differential form of the Gauss law ... 

Dividing the osmotic pressure by the ideal pressure of all counterions, feB /N/Vceii, one obtains the expression for the system osmotic coefficient derived in the framework of the two-zone model... 

From Equation 28 it may be observed that the rate of drug release from an osmotically controlled system is directly proportional to the osmotic pressure within the tablet. As a result the osmotic pressure is an important design consideration for these systems. Osmotic pressure is a colligative property and is therefore dependent on the number of ions and molecules in solution. If the solubility of the drug is low, the inherent osmotic pressure within the tablet will be low and therefore the rate of drug release will be low. Under these conditions the inclusion of excipients, e.g., mannitol, sodium chloride, potassium chloride or hydrophilic polymers, is required within the tablet core. Upon dissolution within the tablet the osmotic pressure will increase thereby enhancing the rate of release of the therapeutic agent (a.47, a. 167). 

A third exponent y, usually called the susceptibility exponent from its application to the magnetic susceptibility x in magnetic systems, governs what m pure-fluid systems is the isothennal compressibility k, and what in mixtures is the osmotic compressibility, and detennines how fast these quantities diverge as the critical point is approached (i.e. as > 1). 

Osmotic pressure is one of four closely related properties of solutions that are collectively known as colligative properties. In all four, a difference in the behavior of the solution and the pure solvent is related to the thermodynamic activity of the solvent in the solution. In ideal solutions the activity equals the mole fraction, and the mole fractions of the solvent (subscript 1) and the solute (subscript 2) add up to unity in two-component systems. Therefore the colligative properties can easily be related to the mole fraction of the solute in an ideal solution. The following review of the other three colligative properties indicates the similarity which underlies the analysis of all the colligative properties ... 

First, we consider the experimental aspects of osmometry. The semiperme-able membrane is the basis for an osmotic pressure experiment and is probably its most troublesome feature in practice. The membrane material must display the required selectivity in permeability-passing solvent and retaining solute-but a membrane that works for one system may not work for another. A wide variety of materials have been used as membranes, with cellophane, poly (vinyl alcohol), polyurethanes, and various animal membranes as typical examples. The membrane must be thin enough for the solvent to pass at a reasonable rate, yet sturdy enough to withstand the pressure difference which can be... 

Figure 8.9 is a plot of osmotic pressure data for a nitrocellulose sample in three different solvents analyzed according to Eq. (8.87). As required by Eq. (8.88), all show a common intercept corresponding to a molecular weight of 1.11 X 10 the various systems show different deviations from ideality, however, as evidenced by the range of slopes in Fig. 8.9. 

The solute molecular weight enters the van t Hoff equation as the factor of proportionality between the number of solute particles that the osmotic pressure counts and the mass of solute which is known from the preparation of the solution. The molecular weight that is obtained from measurements on poly disperse systems is a number average quantity. 

We consider this system in an osmotic pressure experiment based on a membrane which is permeable to all components except the polymeric ion P that is, solvent molecules, M" , and X can pass through the membrane freely to establish the osmotic equilibrium, and only the polymer is restrained. It does not matter whether pure solvent or a salt solution is introduced across the membrane from the polymer solution or whether the latter initially contains salt or not. At equilibrium both sides of the osmometer contain solvent, M , and X in such proportions as to satisfy the constaints imposed by electroneutrality and equilibrium conditions. 

Neglecting the higher-order terms, we can write the osmotic pressure for this three-component system in terms of the van t Hoff equation ... 

What makes the latter items particularly important is the fact that the charge and electrolyte content of an unknown polymer may not be known hence it is important to design an osmotic pressure experiment correctly for such a system. It is often easier to add swamping amounts of electrolyte than to totally eliminate all traces of electrolyte. Under the former conditions a true molecular weight is obtained. Trouble arises only when the experimenter is indifferent toward indifferent electrolyte this sort of carelessness can be the source of much confusion. 

Use the method described in Problem 9 to obtain values of and p from these data. How do the values of these parameters compare with the values obtained for the same system from osmotic pressure data in Problem 8 ... 

Calcium sources, such as gypsum and lime, promote cation exchange from sodium clay to a less-sweUing calcium clay. Calcium concentrations ate normally low (<1000 mg/L) and osmotic swelling is only reduced if other salts are present. Calcium chloride has been used infrequently for this purpose but systems are available that allow high calcium chloride levels to be carried in the mud system (98). 

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... 

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