Tonicity osmotic pressure

Ophthalmic Dosage Forms. Ophthalmic preparations can be solutions, eg, eye drops, eyewashes, ointments, or aqueous suspensions (30). They must be sterile and any suspended dmg particles must be of a very fine particle size. Solutions must be particle free and isotonic with tears. Thus, the osmotic pressure must equal that of normal saline (0.9% sodium chloride) solution. Hypotonic solutions are adjusted to be isotonic by addition of calculated amounts of tonicity adjusters, eg, sodium chloride, boric acid, or sodium nitrate. 

Fluids can be classified further according to their tonicity. Isotonic solutions (i.e., normal saline or 0.9% sodium chloride [NaCl]) have a tonicity equal to that of the ICF (approximately 310 mEq/L or 310 mmol/L) and do not shift the distribution of water between the ECF and the ICF. Because hypertonic solutions (i.e., hypertonic saline or 3% NaCl) have greater tonicity than the ICF (greater than 376 mEq/L or 376 mmol/L), they draw water from the ICF into the ECF. In contrast, hypotonic solutions (i.e., 0.45% NaCl) have less tonicity than the ICF (less than 250 mEq/L or 250 mmol/L) leading to an osmotic pressure gradient that pulls water from the ECF into the ICF. The tonicity, electrolyte content, and glucose content of selected fluids are shown in Table 24—3. 

The tension or osmotic pressure of a solution also, ionic strength, usually measured as weight percentage. Often the tonicity of a solution is presented as relative to some physiological solution (e.g., blood plasma). See Hypertonic Hypotonic Isotonic Isotonic Buffers... 

Several factors of design and manufacture are of great importance sterility, absence of pyrogens and foreign particulate matter, and tonicity. The last, when adjusted to the osmotic pressure of body fluids in the case of aqueous solutions, reduces the risk of tissue irritation and pain,... 

The osmolality of tears is of prime importance, since optical integrity of the cornea is significantly influenced by the tonicity of the tears. The normal osmolality of tears varies from 290 to 310 mOsmkg-1, which is almost equivalent to that of normal saline solution. Variations in osmotic pressure between 100-640 mOsmkg 1 appear to be well tolerated by the eye beyond these values irritation takes place, eliciting reflex tears and reflex blinking. 

The combination of active drug, preservative, and vehicle usually results in a hypotonic formulation (< 290 mOsm). Simple or complex salts, buffering agents, or certain sugars are often added to adjust osmolarity of the solution to the desired value. An osmolarity of 290 mOsm is equivalent to 0.9% saline, and this is the value sought for most ophthalmic and intravenous medications.The ocular tear film has a wide tolerance for variation in osmotic pressure. However, increasing tonicity above that of the tears causes immediate dilution by osmotic water movement from the eyelids and eye. Hypotonic solutions are sometimes used to treat dry eye conditions and to reduce tear osmolarity from abnormally high values. 

The four colligative properties that are of importance are 1) the vapor pressure lowering 2) the elevation of boiling point 3) the freezing-point depression and 4) the osmotic pressure. An attempt is made below to describe qualitatively and quantitatively each colligative property of solutions, with an emphasis on their interrelationship and their application later in measurement and adjustment of the tonicity of solutions, with particular reference to parenteral formulations. Although theoretical derivations based on thermodynamics can be used to show how each of the colligative properties of solution arises and relate to each other, textbooks on physical chemistry for theoretical derivations are recommended. 

Boiling-point elevation can also be used to measure osmotic pressure and tonicity of a solution using just a reflux condenser and a thermometer. The commercially available instrument is the Cottrell boiling-point apparatus. However, this method is affected by the ambient barometric pressure and the presence of volatile solvents in the solution. 

The osmotic pressures of many of the products of Table 3.1 are in excess of that of plasma (291 mosmol dm ). It is generally recommended that any fluid with an osmotic pressure above 550 mosmol dm should not be infused rapidly as this would increase the incidence of venous damage. The rapid infusion of marginally hypertonic solutions (in the range 300-500 mosmol dm ) would appear to be clinically practicable the higher the osmotic pressure of the solution within this range, the slower should be its rate of infusion to avoid damage. Patients with centrally inserted lines are not normally affected by limits on tonicity as infusion is normally slow and dilution is rapid. 

Osmotic pressure is expressed as osmolarity or osmolality. Osmolality is the concentration of body fluids. Tonicity is the effect bodily fluid has on cellular volume and is used to measure the concentration of intravenous solutions. Serum osmolality instead of tonicity is used to indicate the concentration of solutes in body fluids. 

Normal individuals possess a regulatory mechanism that maintains the osmotic pressure of the body fluid at a relatively constant level. This mechanism prevents cells from shrinking or swelling in response to changes in the osmolarity of the body fluid. The water balance is partly regulated by excreting urine of varying tonicities. The urine is diluted in overhydration (decreased osmotic pressure) and is concentrated in dehydration (increased osmotic pressure). Urinary tonicity is controlled by the antidiuretic hormones of the posterior hypophysis. 

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. 

In biology and biochemistry, the term tonicity is used for substances that cannot cross cell membranes and it is a measure of the osmotic pressure that a substance can exert across a cell membrane, compared with blood plasma. In practice, plasma has an osmolarity of about 3 X 10 osmol.m therefore a 1.5 x 10" mol.m NaCl solution may be said to be isotonic with plasma, assuming that neither Na nor Cl" can cross cell membranes, which is nearly true. If a substance can cross a plasma membrane, then it cannot exert an osmotic pressure across that membrane. The solute will equilibrate across the membrane instead of forcing water to move. Urea exhibits such behavior so a 3 x 10 mol.m Wea solution maybe said to be iso-osmotic with plasma but it is not isotonic. 

The significance of a is bettei understood when we study the osmotic behavloui of living cells. Living cells have selectively permeable membranes which are very permeable to water and some low molecular weight solutes, but much less permeable to other substances. This leads to the inflow of some solute molecules along with the solvent while others are retained. Under these cohdltlons, the solution exhibits only that fraction of its total osmotic pressure that is due to the solutes which are retained. This fraction of the total osmotic pressure of a solution is termed as its tonicity. If the cells are placed in a medium whose osmotic pressure matches that of the cell contents inside, there is no unidirectional flow of solvent and the cell size remains the... 

The three aqueous tonic solutions represented below have total volumes of 25. mL for A, 50. mL for B, and 100, mL for C. If each sphere represents 0.010 mol of ions, calculate (a) the total molarity of tons for each solution (b) the highest molarity of solute (c) the lowest molality of solute (assuming the solution densities are equal) (d) the highest osmotic pressure (assuming ideal behavior). 

Osmotic pressure is more important than a considerable concentration of salts for luminescence, growth, and respiration, inasmuch as these processes are not very greatly affected when the tonicity is maintained by sucrose instead of by salts (129). In solutions of increasing hypotonicity luminescence undergoes a diminution more readily than respiration, while the opposite is true in solutions of increasing hypertonicity. Viability is the last to be affected in either case. 

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