Osmotic value

To isolate intact organelles, it is important for the homogenization solution to be isotonic—I e the osmotic value of the buffer has to be the same as that of the interior of the cell. If hypotonic solutions were used, the organelles would take up water and burst, while in hypertonic solutions they would shrink. 

In relation to yeast strain selection, few studies have been conducted on this subject. It will be necessary to find/isolate yeast strains more resistant to, and with better fermentation performance under the harsh conditions of mead production, such as high osmotic values and low nitrogen content. Breeding may be an option. 

Perfusion solution used in microdialysis experiments vary widely in composition and pH. Ideally the composition, ion strength, osmotic value and pH of the perfusion solution should be as close as possible to those of the extracellular fluid of the dialyzed tissue. Perfusion fluids should be at body temperature. 

Soluble substances influence the course of physiological phenomena also by changing the osmotic value of water and its capability to absorb gases. Substances which are unimportant from the viewpoint of biochemistry or toxicology also participate in these effects since they do not metabolize at all or only slightly. 

All aquatic organisms tolerate only a certain range of osmotic values of neighbouring water, which means that they tolerate only certain limited concentrations of dissolved substances, particularly salts [24]. At a higher concentration (hypertonic) the osmotic value of the environment increases and the organisms are damaged or die because of the loss of water drawn from their cells. At too low concentration (hypotonic) the net osmotic flow of water is reversed and water endeavours to overfill and swell the cells, even to bursting point. 

Medicine solutions for nebulisation may contain several additives such as co-solvents, solubilising and stabilising agents, antimicrobial preservatives, salts and pH-regulators to adjust the acidity and tonicity of the solution. Additives may contribute to the osmotic value. Both high and low osmotic values can produce cough and bronchoconstriction... 

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. 

Nose drops and sprays that are not iso-osmotic have a negative influence on the ciliary epithelium. Hypo-osmotic solutions however are more ciliotoxic than hyper-osmotic ones [32]. Again the requirements should be more strict than for eye drops, because the diluting effect of the nasal liquid is much smaller than that of tears. Nasal drops are made iso-osmotic with sodium chloride, or in case of incompatibilities with glucose or mannitol. More information about osmotic pressure and tonicity, and the calculatimi of the osmotic value of solutions, is given in Sect. 18.5. 

The most used ear drops prepared in pharmacies are discussed for their formulation (solvent, pH, osmotic value, preservation), method of preparatiOTi, packaging, storage and methods of administration. 

Ear drops for the middle ear should preferably be iso-osmotic, or at least between the osmotic value of 260 milliosmols and 460 milliosmols (a 0.8 % and a 1.4 % solution of sodium chloride). Substances used to adjust the pH or the osmolarity are the same as those used in eye drops. 

Eye Eye drops Eye ointment Eye lotion Eye cream Eormulation Preparation Tear film Biopharmaceutics Osmotic value Lachrymal secretion... 

Addition of the excipients mentioned in Table 10.5 increases the osmotic value of the preparation. Due to... 

Exact buffer compositions and osmotic values are reported in [66]. 

The preservative selected reduces the choice of other excipients required to adjust pH and osmotic values. Table 10.9 shows the possible combinations of preservatives, pH modifiers and excipients that can add up... 

The osmotic value (see Sect. 18.5) of ophthalmic solutions should be in the range equivalent to 0.5-2 % sodium chloride solution in order to avoid pain sensation. However, in practice the upper limit should be set to 1.6 % NaCl to make sure the eye drops are well tolerated by all patients. 

The volume of enemas may vary from a few millilitres (micro-enema) to more than 100 mL, mainly depending on the intended effect systemic or local. For large-volume enemas water is commonly used and a water-soluble form of the active substance is preferred. The solubility may be increased by addition of co-solvents, to be applied in small volume enemas. If a soluble active substance or an adequate co-solvent cannot be found, a suspension may be prepared. If this is also not an option, a lipophilic vehicle may be chosen. Choice of pH depends on the chosen form of the active substance and is important for the absorption. Excipients may be added to correct the osmotic value, to increase the viscosity, to prevent oxidation or for preservation. 

For rectal administration, the osmotic value may vary within wide limits. An osmotic value corresponding to a 0-1.8 % sodium chloride solution is tolerated. Adjusting the iso-osmotic value of an enema, by addition of, for example, sodium chloride, offers no advantage regarding activity and irritation, and can be omitted. StrrMig hyperosmotic solutions must be avoided in enemas, except for those intended as laxative. A strrMigly hyperosmotic solution, for example a phosphate enema, induces a defecation reflex. The osmotic value of this enema is about seven times higher than that of a normal saline solution. 

As a measure of the tonicity of blood one can calculate with the osmotic value because active substances and additives cannot pass the membrane of the erythrocyte (see Sect. 18.5.2). The osmotic value of blood is around 290 mOsm/kg. Some parenteral fluids however contain substances that can pass the membrane fast ethanol, glycerol, urea. Hyperosmotic solutions of these substances may cause haemolysis so they are hypotonic. The iso-osmotic concentration of ethanol is for example 1.39 % m/m. Ethanol 5 % v/v infusion fluid is therefore hyperosmotic but appears to be practically isotonic. 

Parenteral products with osmotic values differing from the physiological value may cause phlebitis and irritation. This is especially applicable when the injection remains relatively long at the site of injection such as after subcutaneous, intramuscular, epidural and intrathecal administration. There is a higher chance of phlebitis in small vessels after intravenous administration. However, it is not known which limits should be considered to prevent phlebitis and irritation. According to some sources [22] the osmolarity of an intravenous injection should not be higher than 500 mOsm/kg. For subcutaneous and intramuscular administration the range is smaller. 

As is the case for the pH level and buffer capacity, adjustment of osmotic value to physiological conditions is advisable. Sodium chloride or glucose are mostly used to adjust tonicity of parenterals. Sometimes deviating medical requirements are to be met. For example, hyperbaric solutions of local anaesthetics are used in spinal anaesthesia (see Sect. 13.2.4). Hyperbaricity in comparison to the cerebrospinal fluid is achieved by a high glucose concentration (7.5 %) which is also a hyperosmolar. 

The alcoholic nitroglycerin solution 10 mg/g contains 90 % / ethanol (= 86.5 % m/m). The nitroglycerin infusion concentrate thus contains 86.5 mg ethanol per ml. It has an osmotic value of 1,800 mosmol/1 and is thus hyper osmotic, but at the same time hypotonic because ethanol can pass the erythrocyte membrane freely. This solution can only be administered when it is mixed with NaCl 0,9 % or glucose 5 %. 

Registration authorities invite the manufacturer to include pH and osmotic value of the product in the packaging leaflet The pH and the osmotic value of the undiluted as well as the ready to administer product are important in order to estimate the chance of phlebitis. The information about pH is also useful for investigating the possibility of mixing reconstituted products. 

Irrigations to rinse a surgical area or a deep wound should be iso-osmotic. For disinfection or cleansing of superficial wounds this is not strictly necessary. Historically, a sterile hyperosmotic solution (NaCl 3 %, for example) is prepared for rinsing superficial moist wounds and bedsores. Hypertonicity is in fact the mechanism of action the solution has a desiccating effect. For irrigations for the bladder iso-osmosis is less important. Hypo-osmosis is more problematic than hyper-osmosis, because the osmotic value of urine is twice to trice the osmotic value of blood [4]. 

Excipients used and compositimi of the injection (formulation solvent or vehicle, osmotic value, viscosity, pH, surfactants, etc.)... 

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