Isotonic Solutions
Isotonic solutions
Objectives
• Determine the sodium chloride equivalent of a substance from the
volume of isotonic solution that can be made from 1g of that substance.
• Apply the sodium chloride equivalent method to determine the amount
of NaCl needed to make a solution isotonic with body fluids.
• Apply the NaCl equivalent method to determine the amount of substance
other than NaCl (tonicity agent) needed to make a solution isotonic with
body fluids.
• Calculate the volume of water to be added to a given amount of drug to
make an isotonic solution
• Use the freezing point depression of 1% w/v solutions of drugs in
calculations of isotonic solutions.
• Determine if a solution is hypotonic, isotonic or hypertonic
• When a solvent passes through a semipermeable membrane from a
dilute solution into a more concentrated one, the concentrations
become equalized and the phenomenon is known as osmosis.
• The pressure responsible for this phenomenon is termed osmotic
pressure and varies with the nature of the solute.
If the solute is a nonelectrolyte, its solution contains only molecules
and the osmotic pressure varies with the concentration of the solute.
• If the solute is an electrolyte, its solution contains ions and the
osmotic pressure varies with both the concentration of the solute and
its degree of dissociation.
• Thus, solutes that dissociate present a greater number of particles in
solution and exert a greater osmotic pressure than undissociated
molecules.
• Like osmotic pressure, the other colligative properties of solutions,
vapor pressure, boiling point, and freezing point, depend on the
number of particles in solution.
• Therefore, these properties are interrelated and a change in any one
of them will result in a corresponding change in the others.
Isotonic solutions
Isotonic solutions
• Colligative properties, From Greek word" collected together”, depend mainly
on the number of particles in solution.
• Nonelectrolytes, the solution will contain only molecules, and the osmotic
pressure will vary only with concentration of the solute.
• Electrolytes: solution will contain ions, and the osmotic pressure of the solution
will vary not only with the concentration but also with the degree of
dissociation of the solute.
• Isosmotic solutions: solutions that have the same osmotic pressure
• Isotonic solution: a solution having the same osmotic pressure as a specific
body fluid
• Hypotonic solution: a solution of lower osmotic pressure than that of body
fluids.
• Hypertonic solution: a solution of higher osmotic pressure than that of body
fluids.
• Pharmaceutical dosage forms intended to be added directly to the blood or
mixed with biological fluids of the eye, nose, and bowel are of principal
concern to the pharmacist in their preparation and clinical application.
• Important for the pharmacist for preparation of ophthalmic, nasal, parenteral
and some rectal preparations.
Isotonic solutions
Examples of isotonic pharmaceutical preparations
• Ophthalmic solutions
• Aqueous solutions applied to mucosal membranes of the nose, or to
areas of broken skin
• Some solutions for rectal use (enemas)
• Parenteral solutions to be given IV, IM, IC, IT
Special Clinical Considerations of Tonicity
• It is generally accepted that for ophthalmic and parenteral
administration, isotonic solutions are better tolerated by the patient
than those at the extremes of hypo- and hypertonicity.
• With the administration of an isotonic solution, there is a
homeostasis with the body’s intracellular fluids. Thus, in most
instances, preparations that are isotonic, or nearly so, are preferred.
• However, there are exceptions, as in instances in which hypertonic
solutions are used to ‘‘draw’’ fluids out of edematous tissues and into
the administered solution.
• Most ophthalmic preparations are formulated to be isotonic, or
approximately isotonic, to duplicate ophthalmic tears for the comfort
of the patient.
• These solutions are also prepared and buffered at an appropriate
pH, both to reduce the likelihood of irritation to the eye’s tissues and
to maintain the stability of the preparations.
• Injections that are not isotonic should be administered slowly and in
small quantities to minimize tissue irritation, pain, and cell fluid
imbalance. The tonicity of small-volume injections is generally
inconsequential when added to large-volume parenteral infusions
because of the presence of tonic substances, such as sodium chloride
or dextrose in the large-volume infusion, which serve to adjust the
tonicity of the smaller added volume.
• Intravenous infusions, which are hypotonic or hypertonic, can have
profound adverse effects because they generally are administered in
large volumes.
• Large volumes of hypertonic infusions containing dextrose, for
example, can result in hyperglycemia, osmotic diuresis, and excessive
loss of electrolytes.
• Excess infusions of hypotonic fluids can result in the osmotic
hemolysis of red blood cells and surpass the upper limits of the
body’s capacity to safely absorb excessive fluids.
• Even isotonic fluids, when infused intravenously in excessive volumes
or at excessive rates, can be deleterious due to an overload of fluids
placed into the body’s circulatory system
ISOTONICITY CALCULATIONS SUMMARY
Step 1. Calculate the amount (in grams) of sodium chloride
represented by the ingredients in the prescription. Multiply the
amount (in grams) of each substance by its sodium chloride equivalent.
• Step 2. Calculate the amount (in grams) of sodium chloride, alone,
that would be contained in an isotonic solution of the volume specified
in the prescription, namely, the amount of sodium chloride in a 0.9%
solution of the specified volume. (Such a solution would contain 0.009
g/mL.)
• Step3.Subtract the amount of sodium chloride represented by the
ingredients in the prescription (Step 1) from the amount of sodium
chloride, alone, that would be represented in the specific volume of an
isotonic solution (Step 2). The answer represents the amount (in
grams) of sodium chloride to be added to make the solution isotonic.
• Step 4. If an agent other than sodium chloride, such as boric acid,
dextrose, or potassium nitrate, is to be used to make a solution
isotonic, divide the amount of sodium chloride (Step 3) by the sodium
chloride equivalent of the other substance.
Isotonic solutions
• Calculations for preparation of isotonic solution:
• Calculate the number of grams of NaCl used to cause a solution
isotonic,
• multiply the quantity of each drug in the prescription by it’ssodium
chloride equivalent E-value ,
• and subtract this value from the concentration of sodium chloride which is
isotonic with body fluids (0.9 gm per 100 ml).
• How many grams of sodium chloride should be used in compounding the
following prescription
• R/ Pilocarpine nitrate 0.3 g
• Sodium chloride q.s.
• Purified water 30 ml
• Make isoton. Sol.
• Sig. for the eye
Isotonic solutions
• Calculations for preparation of isotonic solution:
Example: How many grams of sodium chloride should be used in compounding the
following prescription
R/ Pilocarpine nitrate 0.3 g
Sodium chloride q.s.
Purified water 30 ml
Make isoton. Sol.
Sig. for the eye
• Sod. Chloride equivalent for Pilocarpine nitrate = 0.23
• 1- 0.23 X 0.3 = 0.069 g of NaCl represented by the pilocarpine nitrate
• 2- 0.9 g NaCl 100 ml water to be isotonic
Xg 30 ml
X = 0.9 X 30 / 100 = 0.27 g
• 3- 0.27 - 0.069 = 0.201 g of sodium chloride to be used
PRACTICE
How many grams of potassium nitrate could be used to make the
following prescription isotonic?
Rx Sol. Silver Nitrate 60
1: 500 w/v Make isoton. sol.
Sig. For eye use.
E value =0.33 silver niitrate
E value = 0.58 potassium nitrate
SOLUTION
The prescription contains 0.12 g of silver nitrate.
Step 1. 0.33 x 0.12 g = 0.04 g of sodium chloride represented by silver
nitrate
Step 2. 60 x 0.009 = 0.54 g of sodium chloride in 60 mL of an isotonic
sodium chloride solution
Step 3. 0.54 g (from step 2) - 0.04 g (from step 1) 0.50 g of sodium
chloride required to make solution isotonic
(Because, in this solution, sodium chloride is incompatible with silver
nitrate, the tonic agent of choice is potassium nitrate.)
Therefore, Step 4. 0.50 g ÷ 0.58 (sodium chloride equivalent of
potassium nitrate) = 0.86 g of potassium nitrate to be used, answer.
Use of Freezing Point Data in Isotonicity
Calculations
• Freezing point data ( ΔTf ) can be used in isotonicity calculations
when the agent has a tonicic effect and does not penetrate the
biologic membranes in question (e.g., red blood cells).
• As stated previously, the freezing point of both blood and lacrimal
fluid is - 0.52°C.
• Thus, a pharmaceutical solution that has a freezing point of -0.52°C is
considered isotonic.
• Representative data on freezing point depression by medicinal and
pharmaceutical substances are presented in Table 11.2.
• Although these data are for solution strengths of 1% (Δ Tf 1%), data
for other solution strengths and for many additional agents may be
found in physical pharmacy textbooks and in the literature.
• Freezing point depression data may be used in isotonicity calculations
as shown by the following.
FREEZING POINT DEPRESION OF 1% SOLTNS
Isotonic solutions
Example Calculations Using Freezing Point Data
How many milligrams each of sodium chloride and dibucaine hydrochloride
are required to prepare 30 mL of a 1% solution of dibucaine hydrochloride
isotonic with tears?
To make this solution isotonic, the freezing point must be lowered to -
0.52°.
From Tables it is determined that a 1% solution of dibucaine hydrochloride
has a freezing point lowering of 0.08°. Thus, sufficient sodium chloride
must be added to lower the freezing point an additional
0.44° (0.52°- 0.08°).
Also from Tables, it is determined that a 1% solution of sodium chloride lowers the
freezing point by 0.58°. By proportion:
1% (NaCl) = 0.58
x% (NaCl) 0.44
x = 0.76% (the concentration of sodium chloride needed to lower the freezing point
by 0.44 required to make the solution isotonic)
Isotonic solutions
Thus, to make 30 mL of solution,
30 mL x 1% = 0.3 g = 300 mg dibucaine hydrochloride, and
30 mL x 0.76% = 0.228 g = 228 mg sodium chloride, answers.
ANY QUESTIONS
