Isotonic, buffer and electrolyte

solutions

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Learning objectives
 Upon successful completion of this chapter, the student will be
able to:
 Differentiate between the terms isotonic, hypertonic, and
hypotonic.
 Calculate dissociation constant
 Perform the calculations required to prepare isotonic
compounded prescriptions.
 State the buffer equation and apply it in calculations.

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Introduction
Solution –
 is a mixture of one or more solutes dissolved in a solvent.
 There are different types medications that can be used as solution
types of dosage form.
 They can be used for parentral, opthalmic, nasal, rectal and
otic routes of administration.

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Cont’d…

 After application usually there is a higher concentration of solutes

on one side of the membrane than the other.

 If the total concentration of all dissolved solutes is not equal on

both sides, there will be net movement of water(solvent) molecules

into or out of the cell.

 This flow can be by diffusion or osmosis.

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Cont’d…
A. Diffusion is the movement of particles from an region of higher
concentration to one of lower concentration.

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 Cont’d…
B. Osmosis is the flow of a solvent from a dilute solution into a more
concentrated solution, through a semipermiable membrane.
 Then the concentrations become equalized.

• Osmotic pressure: -

 the pressure of a solution against a semipermeable membrane to

prevent water from flowing inward across the membrane.

 pressure responsible for osmosis(that stops the process of

osmosis)

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Cont’d…
Tonicity: -
 a measure of the amount of substance dissolved in a liquid (in
most cases water)
 a measure of the effective osmotic pressure gradient of two
solutions separated by a semi permeable membrane.

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 Cont’d…
 There are three classifications of tonicity that one solution can
have relative to another. The three are;
 hypertonic,
 hypotonic, and
 isotonic
 Whether there is net movement of water into or out of the cell and
which direction it moves depends on whether the cell’s
environment is isotonic, hypotonic, or hypertonic

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Cont’d…
A hypotonic solution:,
 Solution that have a lower concentration of solutes than the cell.
 Solutions that have lower osmotic pressure than that of a body
fluid.
 The cell will also have a higher osmotic pressure (the tendency
for water to move into a cell by osmosis than the solution
surrounding it).
 This will cause fluid to move into the cell.

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 Cont’d…
Hypertonic solution:-
 Solution that have a higher concentration of solutes than the cell
and will have a higher osmotic pressure outside the cell than inside
the cell.
 It is a solution of higher osmotic pressure than that of body fluids.

Isotonic solution: -
 Solution having the same osmotic pressure as a specific body fluid.

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Animal and plant cells within solution of different tonicity

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 Cont’d…

 Many solutions intended to be mixed with body fluids, such as

ophthalmic and parenteral administration, are designed to have the
same osmotic pressure for greater patient comfort, efficacy, and
safety
 i.e. minimize tissue irritation, pain and cell fluid imbalance
 So, solution to be mixed with body fluids should have the same
osmotic pressure with body fluids.

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 Physical/chemical considerations in the
preparation of isotonic solutions
 The calculations involved in preparing isotonic solutions may
be made in terms of data relating to the colligative properties
of solutions.
Colligative properties of solutions
 From Greek word" collected together”,
 Properties that depend upon the concentration of solute
molecules or ions, but not upon the identity of the solute.

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Cont’d…
 It includes;
 freezing point depression,
 boiling point elevation,
 vapor pressure lowering, and osmotic pressure.
 Theoretically, any one of these properties may be used as a basis
for determining tonicity.

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 Cont’d…
 Osmotic pressure is one of colligative properties of solutions that
may be used as a basis for determining tonicity in isotonic solution
preparation.
 It depends on 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.

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 Cont’d…
 Thus, solutes that dissociate present a greater number of particles in
solution and exert a greater osmotic pressure than undissociated
molecules.

Methods for adjusting isotonicity

I. Freezing point depression (lowering) method
II. Sodium chloride equivalent method

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 Freezing point determining tonicity in isotonic
solution preparation
 Practically and most conveniently, a comparison of freezing points
is used for determining tonicity.
 It is generally accepted that -0.52 oC is the freezing point of both
blood serum and lacrimal fluid.
 It is assumed that any aqueous solution freezing at -0.52 oC is
isotonic with blood.
 It is rare that a simple aqueous solution of the therapeutic agent to
be injected into body fluid has a freezing point of -0.52 oC
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 Cont…

 To obtain this freezing point

 Add some other therapeutically inactive solute if the solution
is hypotonic (freezing point above -0.52 oc) or
 Dilute the solution if it is hypertonic (freezing point below -
0.52 oc).
 The usual practice is to add either sodium chloride or dextrose
to adjust hypotonic solutions to isotonic.

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Cont..

• If the concentration and the corresponding freezing point dep.

of a solution are known, the concentration of the isotonic
solution with a specific body fluid can be calculated using the
following relationship

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Examples
I. 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?(fpNacl=0.58
fpdibucaine=0.08) by proportion:

note = =0.52-0.08=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)
 30 g*0.76=228 mg sodium chloride.

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 Sodium chloride equivalent method
 A sodium chloride equivalent, E value, is defined as the
weight of sodium chloride that will produce the same osmotic
effect as 1 g of the drug.
 can be obtained from tables in pharmaceutical calculations
texts.
 It can be also calculated using the following formula

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 Cont..
 NB: i is dissociation value (ionization value);
 MW is molecular weight
 The i value for substances can be estimated:
 Non electrolytes and substances of slight dissociation: 1.0
 Substances that dissociate into 2 ions: 1.8
 Substances that dissociate into 3 ions: 2.6
 Substances that dissociate into 4 ions: 3.4
 Substances that dissociate into 5 ions: 4.2

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Examples
 Calculate the sodium chloride equivalent for timolol
maleate, which dissociates into two ions and has a
molecular weight of 432.
Timolol maleate, i factor 1.8
58.5/1.8 =1.8/432
=0.14, answer

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Cont..
The calculation of isotonic solutions with sodium chloride
equivalent may be outlined as follows:
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

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 Cont..
Step 2. Calculate the amounts of sodium chloride, alone, that
would be contained in an isotonic solution of the volume
specified in the prescription, namely, the amount of NaCl in a
0.9% solution of the specified volume
Step 3. 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 isotonicTI

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Cont..

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

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 Examples

1.How many grams of sodium chloride should be used in

compounding the following prescription
Pilocarpine nitrate 0.3 g

Sodium chloride q.s.

Rx Purified Water ad 30 mL
Make isoton. Sol.
Sig. for the eye

Sod. Chloride equivalent for Pilocarpine nitrate = 0.23

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Cont’d…
Soln;

The procedure for the calculation of isotonic solutions with sodium

chloride equivalents

Step. 1. The amount (in grams) of sodium chloride represented by the

ingredients in prescription

= 0.23 X 0.3g of pilocarpine nitrate

= 0.069 g of NaCl represented by the pilocarpine nitrate

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 Cont’d…

Step. 2- The amount (in grams) of sodium chloride, alone, that would
be contained in an isotonic solution of the volume specified in the
prescription
30 × 0.009 = 0.270 g of sodium chloride in 30 ml of an isotonic
sodium chloride solution
Step. 3; the amount (in grams) of sodium chloride to be added to make
the solution isotonic.
= 0.27 - 0.069 = 0.201 g of NaCl should be used.

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 Cont’d….

Phenacaine Hydrochloride…….1%, (E 0.20)

Rx Chlorobutanol……………………….. ½%,(E 0.24)

Boric Acid……………………………… q.s.,(E 0.52)

Purified Water ad ….......……..60, (E 0.009)

Make isoton. sol.

Sig. One drop in each eye.

• prescription calls for 0.6 g of phenacaine hydrochloride and 0.3 g of

chlorobutanol.

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 Cont…

Step 1)
 0.20 × 0.6g = 0.120g of NaCl represented by phenacaine
hydrochloride
 0.24 × 0.3g = 0.072g of NaCl represented by chlorobutanol
 Total: 0.192 g of NaCl chloride represented by both ingredients

Step 2)
 60×0.009 = 0.540 g of NaCl in 60 ml of an isotonic NaCl
solution

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 Cont..

Step 3)
 0.540 g (from Step 2)-0.192 g (from Step 1)
 =0.348 g of NaCl required to make the solution isotonic.

But because the prescription calls for boric acid:

Step 4)
 0.348 g/0.52 (NaCl equivalent of boric acid)
 = 0.669 g of boric acid to be used.

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Buffer and buffer solution

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 Introduction

pH is a measure of the concentration of H+ [H3O+] ions in a solution.

 Only the concentration of H+ and OH- molecules determine the pH.

 When the concentration of H+ and OH- ions are equal, the solution
is said to be neutral.
 If there are more H + than OH- molecules the solution is acidic, and
if there are more OH- than H + molecules, the solution is basic.

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 Cont’d…

 Substances or combinations of substances in aqueous solution

that imparts to the system the ability to maintain a desired pH at a
relatively constant level are called buffers.
 The ability to resist changes in pH is referred to as buffer action.
 A buffer solution is a solution that resists changes in pH caused
by the addition of small amounts of a strong acid or alkali.

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 Cont’d…

 A buffer solution is usually composed of

a weak acid and a salt of the acid

Eg. acetic acid and sodium acetate, or

a weak base and a salt of the base

Eg. ammonium hydroxide and ammonium chloride.

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 Cont’d…

There are two types of buffers:

1. Acidic
2. Basic
1. Acidic buffers comprise of a weak acid and its salt.
e.g. ethanoic acid and sodium ethanoate.
2. Basic Buffers comprise of a weak base and its conjugate salt.
e.g. aqueous ammonia and ammonium chloride.

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 Advantages of buffer
 The most common buffer systems are used in

I. the preparation of such dosage forms as injections and ophthalmic

solutions, which are placed directly into pH-sensitive body fluids;
II. the manufacture of formulations in which the pH must be
maintained at a relatively constant level to ensure maximum
product stability; and
III. pharmaceutical tests and assays requiring adjustment to or
maintenance of a specific pH for analytic purposes.

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 Cont’d…

 Typical buffer systems that may be used in pharmaceutical

formulations include the following pairs:
acetic acid and sodium acetate,
boric acid and sodium borate, and
disodium phosphate and sodium acid phosphate.

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 pH in the Absence of a Buffer
 If a strong acid or strong base is added to water, the pH will change
dramatically.

HCl + H2O → H3O + + Cl -

 The resulting large concentration of (H +) makes the solution more

acidic and leads to a dramatic drop in the pH.

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 Cont’d…
NaOH + H2O → OH-+ Na+

 The resulting large concentration of OH- makes the solution more

basic and leads to a dramatic increase in the pH.
 As the concentration of OH- ions goes up, the concentration of H +
ions goes down.)
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Change in pH with Addition of an Acid or Base

Buffer equation(Henderson-Hasselbalch equation)

Dissociation constant (Kd) (ionization constant)

 A specific type of equilibrium constant that measures the

propensity of a larger object to separate (dissociate) reversibly into
smaller components, as when a complex falls apart into its
component molecules, or when a salt splits up into its component
ions.

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 Cont’d…

 For the acid dissociation reaction

HA H+ + A-
Ka = [H+][A-]
[HA]
 For the base dissociation reaction
BOH OH- + B +
Kb = [OH-][B+]
[BOH]
NB:
 B+ = salt
 BOH = base

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 Cont’d…
 Not only acids and bases dissociate, water dissociates too: and the
equilibrium of this reaction is described by the equation.

H2O-------- H+ + OH-

K = [H+][OH-]

H2O

 Water ionization constant or water ion product:

Kw = [H+][OH-]

PKw = PH + POH

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 Cont’d…

 The Henderson-Hasselbalch equation is used mostly to calculate pH of

solutions created mixing known amounts of acids and conjugate bases (or
neutralizing part of acid with a strong base).

pKa = -log Ka

Ka = [H+][A-]

[HA]
pKa = -log (H+) – log[salt/acid]

pH = pKa + log[salt/acid]

Kb = [OH-][B+]

[BOH]
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pOH = pKb + log[B+/BOH]
 Cont’d…

E.g. 1, What is the pH of a buffer solution prepared with 0.05 M

sodium borate and 0.005 M boric acid?

The pKa value of boric acid is 9.24 at 25C.

Soln;

pH = pKa + log[salt/acid]

= 9.24 + log[0.05/0.005]

= 9.24 + log10

= 9.24+1

= 10.24, answer. 46
 Cont’d…

E.g. 2, Calculate the pH of a buffer solution made from 0.20 M HC 2H3O2 and

0.50 M C2H3O2- that has an acid dissociation constant for HC2H3O2 of 1.8 x

10-5.

Soln;

pH = pKa + log[salt/acid]

= pKa + log ([C2H3O2-] / [HC2H3O2])

= -log (1.8 x 10-5) + log (0.50 M / 0.20 M)

= -log (1.8 x 10-5) + log (2.5)

= 4.7 + 0.40
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= 5.1
 Cont’d…
E.g. 3, Calculate the change in pH after adding 0.04 mol of sodium
hydroxide to a liter of a buffer solution containing 0.2 M concentrations
of sodium acetate and acetic acid. The pKa value of acetic acid is 4.76 at
25C.

Soln;

The pH of the buffer solution is calculated by using the buffer equation as

follows:

pH = pKa + log[salt/acid]

= 4.76 + log[0.2/0.2]

= 4.76 + log 1

= 4.76 48
 Cont’d…
The addition of 0.04 mol of sodium hydroxide
 converts 0.04 mol of acetic acid to 0.04 mol of sodium acetate; and

 the concentration of acetic acid is decreased and

 the concentration of sodium acetate is increased by equal amounts

pH = pKa + log[(salt + base)/(acid – base)]

= pKa + log[(0.2 + 0.04)/(0.2 - 0.04)]

= pKa + log[0.24/0.16]

= 4.76 + 0.1761

= 4.9361 or 4.94
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 Quiz
1. How many grams of sodium chloride should be used in
compounding the following prescription?
– Chloramphenicol 0.5g
– Sodium Chloride q.s.
– Purified Water ad 50mL
– Make isoton. sol.
– Sig. Eye drops.

sodium chloride equivalent of Chloramphenicol=0.10

04/05/2024 50
Thank you

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