Tonicity PDF

Tonicity Tonicity - ability of a solution to affect fluid volume and pressure within a cell – depends on concentration and permeability of solute Isotonic solution A solution with the same solute concentration as that of the cytosol; normal saline Paratonic solution 1. Hypotonic s...

Tonicity Tonicity - ability of a solution to affect fluid volume and pressure within a cell – depends on concentration and permeability of solute Isotonic solution A solution with the same solute concentration as that of the cytosol; normal saline Paratonic solution 1. Hypotonic solution – lower concentration of nonpermeating solutes than that of the cytosol (high water concentration) – cells absorb water, swell and may burst (lyse) 2. Hypertonic solution – has higher concentration of nonpermeating solutes than that of the cytosol (low water concentration) – cells lose water + shrivel (crenate) 1  If red blood cells are suspended in a hypertonic solution, the water within the cells passes out through the cell membrane in order to dilute the surrounding salt solution and attain an equilibrium across the membrane. This outward passage of water causes the cells to shrink and become wrinkled or crenated. If red blood cells are suspended in a hypotonic solution, water enters the blood cells causing swelling and finally bursting of the cell with the liberation of hemoglobin. This bursting of cells is known as hemolysis. 2  Paratonic solutions (hypertonic or hypotonic) if instilled into the eyes or nose may cause irritation especially if the quantity instilled is large. It is therefore necessary that in addition to being buffered at the desired pH, pharmaceutical solutions that are meant to be introduced into the body or applied to delicate membrane of the body should be isotonic with the physiological fluids (blood, plasma, lachrymal secretion). 3  METHODS OF ADJUSTING TONICITY One of several methods may be used to calculate the quantity of sodium chloride, dextrose, and other substances that may be added to solutions of drugs to render them isotonic. 4  Cryoscopic method: sodium chloride or some other substance is added to the solution of the drug to lower the freezing point of the solution to -0.52° and thus make it isotonic with body fluids.  A- Cryoscopic Method The lachrymal secretion contains several solutes in it and has a freezing point depression of -0.52°C. All solutions, which freeze at -0.52°C, will be isotonic with the lachrymal fluid. Adjustment of tonicity is simplified if the freezing points of the medicament and the inert salt (adjusting substance) are known for various strengths of their solutions. Freezing points are usually expressed in terms of 1% solutions and one can calculate the quantity by multiplying the freezing point with the factor. 6  Example: How much sodium chloride is required to render 100 ml of a 1% solution of apomorphine hydrochloride isotonic with blood serum It is found that a 1 % solution of the drug has freezing point lowering of 0.08°. To make this solution isotonic with blood, sufficient sodium chloride must be added to reduce the freezing point by an additional 0.44° (0.52° - 0.08°). In the freezing point table, it is also observed that a 1% solution of sodium chloride has a freezing point lowering of 0.58°. By the method of proportion: 8  Thus, 0.76% sodium chloride will lower the freezing point the required 0.44° and will render the solution isotonic. The solution is prepared by dissolving 1.0 g of apomorphine hydrochloride and 0.76g of sodium chloride in sufficient water to make 100 ml of solution. 9 B- Sodium Chloride Equivalent Method: A second method for adjusting the tonicity of pharmaceutical solutions was developed by Mellen and Seltzer. The sodium chloride equivalent or, the tonic equivalent of a drug is the amount of sodium chloride that is equivalent to (i.e., has the same osmotic effect as) 1 gram, or other weight unit, of the drug. The sodium chloride equivalents E for a number of drugs are calculated. 10  Example: Calculate the amount of NaCl required to make the following ophthalmic solution isotonic. 1. Determine the amount of NaCl to make 30 ml of an isotonic solution X = 0.27 g 2. Calculate the contribution of atropine sulfate to the NaCl equivalent 30 ml × 2 g/100 ml = 0.6 g atropine sulfate E atropine sulfate = 0.12 0.6 g x 0.12 = 0.072 g 3. Determine the amount of NaCl to add to make the solution isotonic by subtracting (2) from (1) 0.27 g - 0.078 g = 0.198 g or 198 mg 12  Other substances may be used, in addition to or in place of NaCl, to render solutions isotonic. This is done by taking the process one step further and calculating the amount of the substance that is equivalent to the amount of NaCl calculated in step 3. For example, boric acid is often used to adjust isotonicity in ophthalmic solutions because of its buffering and anti-infective properties. If E for boric acid is 0.50, then the amount of boric acid needed to replace the NaCl in step 3 can be calculated: X = 0.38 g or, more simply: 0.192 g ÷ 0.50 = 0.38 g Thus, 0.38 g or 380 mg of boric acid would be required to render the previous ophthalmic solution isotonic. 13  How many grams of boric acid should be used in compounding the following prescription? Rx phenacaine hydrochloride 1% chlorobutanol 0.5% boric acid q.s. purifi ed water, a.d. 60.0 mL make isotonic solution *E for cromolyn sodium = 0.11 *E for benzalkonium chloride = 0.16 *E for mannitol= 0.18 *E for Dextrose = 0.18 *E for monobasic sodium phosphate = 0.42 *E for dibasic sodium phosphate = 0.31