ISOTONICITY
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This document discusses methods for adjusting the tonicity of pharmaceutical solutions to be isotonic with body fluids. It defines isotonic, hypertonic, and hypotonic solutions. Three main methods are described for calculating the concentration needed to achieve isotonicity: 1) Based on freezing point depression measurements, 2) Based on molecular concentration, 3) Based on sodium chloride equivalents. Examples are provided to illustrate how to use the freezing point depression and sodium chloride equivalent methods to determine the amount of sodium chloride required to adjust the tonicity of sample solutions.
ISOTONICITY
- 1. ISOTONICITY METHOD ADJUSTMENT OF TONICITY BY PROF. TAUFIK MULLA ASST. PROFESSOR SPBC COLLEGE OF PHARMACY
- 2. INTRODUCTION In addition to carrying out pH adjustment, pharmaceutical solutions are made for application to delicate membranes of the body should also be adjusted to approximately the same osmotic pressure as that of the body fluids. Isotonic solutions cause no swelling or contraction of the tissues with which they come in contact and produce no discomfort when instilled in the eye, nasal tract, blood, or other body tissues
- 3. OSMOSIS / OSMOTIC PRESSURE The flow of the solvent through a semipermeable membrane from pure solvent to solution or from a dilute solution to concentrated solution is termed osmosis. Osmotic pressure (π) may be defined as the external pressure applied to the solution in order to stop the osmosis of the solvent into the solution separated by a semipermeable membrane. Solutions having the same osmotic pressure are said to be isotonic. In terms of physiological fluids, the solutions having osmotic pressure equal to the osmotic pressure of intracellular fluid is called isotonic solution. (πsoln = πcell) In pharmacy and medical science, isotonic solution is that solution; which have equal tonicity with body fluid i.e. blood, serum, plasma or lacrimal fluid. 0.9% NaCl solution is also regarded as isotonic solution. (0.9 gm of NaCl in 100ml of water)
- 4. HYPERTONIC SOLUTIONS , HYPOTONIC SOLUTIONS , PARATONIC SOLUTIONS As compared to the blood plasma if a solution has higher osmotic pressure is said to be hypertonic solution. Physiological solutions having a greater osmotic pressure than that of body fluid or 0.9% NaCl solution is referred to as hypertonic solution. As compared to the blood plasma if a solution has lower osmotic pressure is said to be hypotonic solution. Physiological solutions with an osmotic pressure lower than that of body fluid or 0.9% NaCl solution is referred to as hypertonic solution. The solution that is not isotonic that means both the hypertonic and hypotonic solutions are called paratonic solution.
- 5. MEASUREMENT OF TONICITY For the preparation of isotonic solutions, the quantities of substances to be added may be calculated by the following methods: 1. Based on the freezing point data (Freezing point depression). 2. Based on molecular concentration. 3. Based on Sodium Chloride equivalents. 4. Graphical method based on vapor pressure and freezing point determinations
- 6. BASED ON FREEZING POINT DEPRESSION The freezing point is a colligative property (colligative properties are those properties of solutions that depend on the ratio of the number of solute particles to the number of solvent particles in a solution) often used in the calculation of the isotonic solution as it can be measured easily and accurately. The temperature at which blood plasma and tears (Lachrymal secretions) freeze is –0.52ºC which is the same value of a 0.9% solution of NaCl. All solutions which freeze at –0.52ºC will be isotonic with blood plasma and lachrymal fluid. The freezing points are usually expressed in terms of 1% solutions Where, a= freezing point depression of unadjusted solution. b= freezing point depression of 1% W/V of the adjusting substance
- 7. EXAMPLE Find out the concentration of NaCl required to render or make a 1% solution of cocaine hydrochloride isotonic with blood plasma. The freezing point of 1% W/V solution of cocaine hydrochloride is -0.090ºC and that of NaCl is –0.576ºC.
- 8. BASED ON SODIUM CHLORIDE EQUIVALENT This method has gained popularity. NaCl method is defined as the weight of sodium chloride which will produce the same osmotic effect as 1 g of the drug to prepare an isotonic solution. For example, potassium chloride has sodium chloride equivalent (E) value of 0.76 gm NaCI / gm of KCI-. This means 0.76 gm of NaCI produce the same osmotic effect as 1 gm of KCI. To make a solution of a particular drug isotonic with blood plasma, the sodium choride equivalent value (E) of that drug is noted from the reference table. This E value is multiplied with the %age of the drug solution, and result so obtained is subtracted from 0.9%. The difference in value so obtained is the amount of NaCI needed to adjust the tonicity of the solution to isotonic value. Amount of NaCI required = 0.9% - {%age of solution x E)
- 9. EXAMPLE Find the amount of sodium chloride needed to make a - solution of 0.5% of KCI isotonic with blood plasma. Sodium chloride equivalent value (E) of KCI is 0.76. Given solution (not isotonic) = 0.5% KCI E value of KCI = 0.76 So, by applying formula, Amount of NaCI required = 0.9 - (%age of drug x E) 0.9 - (0.5 x 0.76) = 0.9 - 0.38 = 0.52 gm Hence, 0.52 gm of NaCI must be added in 0.5% KCI solution to make it isotonic.