Osmotically active substance

The most universal transport systems are those involved in the transport of the ubiquitous inorganic ions, sodium, potassium and calcium1. The sodium pump counteracts passive water movement across the cell membrane by removing sodium ions together with chloride or other anions from the cytoplasm to lower its content of osmotically active substances. In most cells, however, the elimination of sodium ions is connected with an accumulation of potassium ions6. For three sodium ions leaving the cell two potassium ions are taken up9,10). The resulting concentration... 

A combination of osmotic and swelling effects was used in the system developed by Amidon and Leesman. " The permeability-controlled systems consisted of a core, containing an osmotically active substance, a swelling substance, and the drug. NaCl and sorbitol were used as osmotic substances and Na carboxymethyl cellulose as the swelling material. These cores were coated with an insoluble, semipermeable polymer, such as cellulose acetate. The time Tp, when the insoluble film ruptured, was described by the following equation ... 

The mechanism of transport in the sieve tubes has still not been elucidated. Nonetheless most of the presently known findings argue in favor of the correctness of the mass flow hypothesis put forward by Munch in 1926. According to it, convection or mass flow is responsible for the transport in the sieve tubes just as for transport in the xylem or in the blood vessel system of animals. The driving force of this mass flow in the sieve tubes is a concentration gradient of osmotically active substances decreasing in the direction of transport. 

Osmolality is a measure of the number of osmotically active particles per unit of solution, independent of the weight or nature of the particle. Equimolar concentrations of all substances in the undissociated state exert the same osmotic pressure. Although the normal serum osmolality is 280 to 300 mOsm/kg (280 to 300 mmol/kg), multiple scenarios exist where this value becomes markedly abnormal. The calculated serum osmolality helps determine deviations in TBW content. As such, it is often useful to calculate the serum osmolality as follows ... 

The osmotic activity of a dissolved substance is characterized by its osmolarity and/or osmolality and the osmotic pressure. Osmolarity and osmolality are defined as follows ... 

Physiologists studying osmotic relationships of organisms, however, are often concerned with the total concentration of all dissolved substances, not just the concentrations of specific solutes. For expressing the total number of osmotically active particles in a solution, the concept of osmolality is commonly employed to refer to the osmotic pressure characteristic of a solution. One osmole is defined as the osmotic pressure of a 1.0 molal solution of an ideal solute. Because conditions of ideality do not pertain to the case of biological fluids, it is not possible to extrapolate precisely from chemical determinations of moles of solute per kilogram (or liter) of fluid to the osmolality of that fluid. Rather, this value must be determined empirically. 

Further support comes from the studies relating cell wall biosynthesis and amino acid accumulation capacity in vitamin B6-deficient cells, since it is difficult to account for these observations without attributing considerable osmotic activity to the accumulated amino acids. Any description of accumulation which invokes amino acid attachment to intracellular binding sites, whose affinity can be reduced by a vitamin B6 deficiency, must account for the stimulation of uptake that accompanies the synthesis of essentially extracellular cell wall material. If the reduction in affinity occurs because the cell interior becomes overhydrated (a reasonable postulate which follows from the osmotic experiments), the beneficial effect of wall synthesis is not readily explicable, since vitamin B6-deficient cells have a swollen appearance which is not significantly altered after wall synthesis has been stimulated. Thus, the existing overhydration within the cell probably is not reversed by this change. In contrast, the deposition of additional wall substance would prevent further unfavorable consequences of swelling such as membrane distention, and, in this way, forestall the premature cessation of amino acid accumulation. 

The experimentally derived osmotic pressure is frequently expressed as the osmolality which is the mass of solute which, when dissolved in 1 kg of water, will exert an osmotic pressure, H, equal to that exerted by 1 mole of an ideal unionised substance dissolved in 1 kg of water. The unit of osmolality is the osmole (abbreviated as osmol), which is the amount of substance that dissociates in solution to form one mole of osmotically active particles, thus 1 mole of glucose (not ionised) forms 1 osmole of solute, whereas 1 mole of NaCl forms 2 osmoles (1 mole of Na+ and 1 mole of... 

The 9mOsmol/kg added to the above equation represents the contribution of other osmoticaUy active substances in plasma, such as K", Ca " ", and proteins, and 1.86 is two times the osmotic coefficient of Na, reflecting the contributions of both Na and CT. The reference interval for plasma osmolality is 275 to 300mOsmol/kg. Comparison of measured osmolality with calculated osmolality can help identify the presence of an osmolal gap, which can be important in determining the presence of exogenous osmotic substances. Comparison of calculated and measured osmolalities can also confirm or rule out suspected pseudohyponatremia caused by the previously discussed electrolyte exclusion effect. 

The composition of the structural material and the choice of the fabrication process are important in the preparation of controlled-release systems. Over the past decades, great advances have been made in the engineering of multicomponent, polymer-based, structural materials. These materials were designed to release active substances by different mechanisms (ref. 1) including diffusion, chemical control (polymer degradation) and solvent activation (swelling or osmotic pressure). In some cases, combinations of such mechanisms have been used. Experimental methods and theoretical analysis of mass transport phenomena in these materials have been developed (refs. 2,3). 

The physical properties of dilute solutions of certain surface-active substances, when plotLed as a function of solution concentration, show a more or less sharp break, which occurs at roughly the same point lor different properties. Typical examples are the breaks in the curves of surface tension, electrical conductivity, and osmotic pressure, as illustrated schematically in Figure 11.1. The... 

Enemas commonly are employed, either by themselves or as adjuncts to bowel preparation regimens, to empty the distal colon or rectum of retained solid material. Bowel distention by any means will produce an evacuation reflex in most people, and almost any form of enema, including normal saline solution, can achieve this. Specialized enemas contain additional substances that either are osmotically active or irritant however, their safety and efficacy have not been studied in a rigorous manner. Repeated enemas with tap water or other hypotonic solutions can cause hyponatremia repeated enemas with sodium phosphate-containing solution can cause hypocalcemia. 

Micelles. Dilute aqueous solutions of surface-active substances have normal physical properties, but at a higher concentration (characteristic for each substance) there occurs an abrupt change in surface tension, osmotic pressure, and electrical conductivity. These changes are due to the formation of a new, dispersed phase which takes the form of aggregates named micelles. These are often roughly spherical the hydrocarbon chains are in the interior of the sphere and the hydrophilic groups occupy the outside of the micelles in contact with the solvent water. The lowest concentration at which micelle formation occurs is called the critical micelle concentration, an abrupt transition point. 

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. 

A reservoir system consists of an active substance and a membrane, and therefore is also known as a membrane coti-trolled system. A membrane or coating can be applied to a whole tablet or capsule, or to a tablet core. Granulates and even crystals can be coated as well, which are then processed into tablets or capsules. Enteric-coated dosage forms have an acid-resistant coating, which dissolves when the pH is increased. An osmotic system may be regarded as a particular reservoir system, because it has a semi-permeable membrane that is provided with holes with an exact diameter. 

In the formulation of preparations for the oropharynx, taste and texture are features that are important for the acceptance by the patient. Pharmacy preparation can play an important role, because of the advantage that preparations can be tailor made according to the specific situation or taste of the patient. For instance, chemotherapy and several other active substances, may cause dry mouth and stomatitis, and mouthwashes or gels can relieve these problems. However, they should not cause irritation and must be accepted by the patient. This has to be kept in mind when choosing a vehicle, or the pH or the osmotic value of a preparation. 

Nasal drops and liquid nasal sprays are solutions, emulsions or suspensions intended for instillation or spraying into the nasal cavities. Nasal powders or nasal insufflation powders are intended for insufflation into the nasal cavity by means of a suitable device. The size of the particles are such as to localise their deposition in the nasal cavity. In nasal sticks and so-called inhalation ointments mostly volatile active substances are formulated in a fatty base. Nasal washes are generally aqueous iso-osmotic solutions intended to cleanse the nasal cavity. If they are intended for application on injured parts of the mucosa, or prior to a surgical operation, they have to be sterile. Nasal powders and nasal sticks are not very common in pharmacy practice. Therefore they are not discussed in this chapter. 

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