CALCULATION FOR SOLUTION ISOTONIC WITH BLOOD AND TEARS

Some of the many ways;

1. Freezing point depression method
2. NaCl equivalent method
3. White Vincent method
4. Sprowl method
5. Molecules concentration method
6. Graphical method on vapor pressure and freezing point determination

1.

FREEZING POINT DEPRESSION METHOD

The plasma and blood freezing point temperature = -0.52C
The dissolved substances in plasma or tear depress the solution freezing point below 0.52C
Any solution that freeze at T=-0.52C is isotonic with blood and tear
weight of substance that need to be adjusted to make it hypotonic given by the following
formula;

=

0.52 

Where,
W=the weight, in g, of the added substance in 100ml of the final solution
a =the depression of the freezing point of water produced by the medicament already in the
solution (calculated by multiplying the value for b for the medicament by the strength of the
solution express as % w/v)
b=the depression of freezing of water produced by 1 per cent w/v of the added substance

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Freezing Point Depression Method

Example 1.1
Rx
NaCl
Dextrose

Tf 1%
0.576
0.101

900mg
q.s (20.5g)

Ft. isotonic soulution500ml

Or;
0.9%
5
7
=
500
100

Solution;

=

. 


.

.)


. (

.


( = 0.18%
5

= 4.12   100 !" #$"

For 500ml;
= (4.12 )

500
100

= 20.6 &'($)"!' )'*#)'&

Example 1.2
Rx
Ephedrine HCl
1g
Chlorobutol
0.5g
NaCl (1.4g)
q.s
Distilled water q.s ad 200ml

Solution;

=

0.52 
0.52 [(0.5 0.165) (0.25 0.138)]
=

0.576

= 0.7  01  100 !" #$"

2") 200 ;
= (0.7 )

200
100

= 1.4 01 )'*#)'&

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Freezing Point Depression Method

EXercise 1.3
Prepare 500ml NaHCO3 (T.f 1%=0.38) so that when it is dilute with the same amount of water, it would
be isotonic.
Solution;
Rx
NaHCO3
Water qs ad

Xg(13.7)
500ml

T.f 1%
0.38

The solution is hypertonic

When diluted
NaHCO3
Water qs ad

Xg
1000ml

This solution is isotonic

=

0.52  0.52 0
=
= 1.37
9 ! !"$"9
0.38

NaHCO3 required to make the solution isotonic upon dilution is;

1.37

=
100
1000
1.37 X 10 = 13.7g (to be dissolved to 500ml solution)

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Freezing Point Depression Method

2. NaCl EQUIVALENT METHOD (E)

Based on the factor called the sodium chloride equivalent which can be used to convert a
specified concentration of medicament to the concentration of medicament to the
concentration of sodium chloride that will produce the same osmotic effect.
Standard 0.9 % w/v NaCl at isotonic
Method to calculate % at isotonic, Tf 1% =0.576 ~ NaCl

=

0.52  0.52 0
=
= 0.9  ") 0.9%
5

0.576

Known as normal saline

Sodium chloride equivalents (E1%) can be calculated from the following formula;
=

(:)''; <"$ &'<)'!!" <)"&#9'& = !" #$" >, @A1 <. 927)
0.576 (2)''; <"$ &'<)'!!" <)"&#9'& = 01 "2 $' !' !$)'$ )

Formula & Method

= 0.9% - ([E1%X %w/v] + .)

1
Look up in the table the sodium chloride equivalent
for the srenght of solution nearest to the strenght
of medicament in the preparation.

2
Multiply this by the strenght of the medicament.

3
substract the result from 0.9 per cent; the
difference is strenght of sodium chloride necessary
to adjust the solution to iso-osmoticity.

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aCl Equivalent Method

Example 2.1
Tf 1% ascorbic acid =0.105C
Tf 1% NaCl
= 0.576C
What is the E for 1% ascorbic acid?
Solution

.
C

E 1% ascorbic acid=
.C = 0.18
Example 2.2
Rx
NaCl
0.2%w/v
Dextrose q.s
Ft. isotonic solution 500ml

Solution;
Tf 1% NaCl = 0.576C
Tf 1% dextrose = 0.101 C

.
C

For dextrose 1 % (E1%) =

.C = 0.18
Conclusion 1% dextrose has osmotic pressure equals to 0.18% NaCl
NaCl in the solution = 0.2 %
Remaining amount of NaCl to be added for isotonic
0.9% - 0.2% =0.7%
1% dextrose equivalent to 0.18% NaCl
% dextrose equivalent to 0.7% NaCl

Convert amount of NaCl required

to amount of dextrose required

(0.7%)(1%)
= 3.89% &'($)"!'
0.18%

For 500ml;
3.89

=
100
500
= 19.45 g
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aCl Equivalent Method

Example 2.3
Rx
Ephedrine HC
Chlorobutol
NaCl
Distilled water

1g
0.5g
q.s
200ml

E 1%
0.3
0.24
isotonic

Solution;
For ephedrine HCl D

100E % 0.3 = 0.15%

For chlorobutol D

100E % 0.24 = 0.06%

Amount of NaCl for isotonic;
0.9% - (0.15% + 0.06%) = 0.69%
So for 200ml.= 1.38

Example 2.4
Rx
Ephedrine HCl
Chlorobutol
KCl
Distilled water

1g
0.5g
q.s
200ml

E 1%
0.3
0.24
0.4
isotonic

Solution;
1% KCl equivalent to 0.4% NaCl
% 0.69% NaCl (refer to example 3)

Let adjust isotonicity using KCl instead

of NaCl

Convert amount of NaCl required to

amount of KCl required

0.69
= 1.725% F1
0.4

So for 200ml ..= 3.45g KCl

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aCl Equivalent Method

Example 2.5
Calculate the percentage of sodium chloride required to render a 0.5 per cent solution of
potassium chloride iso-osmotic with blood plasma.
Solution
Sodium chloride equivalent of 0.5 per cent potassium chloride = 0.76
Percentage of sodium chloride for adjustment
= 0.9 (0.5 0.76) = 0.9 0.38 = 0.52
Example 2.6
Calculate the percentage of anhydrous dextrose required to render a 1 per cent solution
of ephedrine hydrochloride iso-osmotic with body fluid.
Percentage of sodium chloride for adjustment
= 0.9 (1 0.3) = 0.6
Equivalent percentage of anhydrous dextrose = 0.6/0.18 = 3.33
Example 2.7
Select a suitable substance for an eye lotion 0.5 per cent of silver nitrate and calculate the
percentage required to render the lotion iso-osmotic with lachrymal secretion.
Sodium chloride is unsuitable because silver nitrate is incompatible with chloride.
Potassium nitrate will be used
Sodium chloride equivalent of 0.5 per cent silver nitrate = 0.33
= 0.9 (0.5 0.33) = 0.9 0.165 = 0.753
Equivalent percentage of potassium nitrate =

.G

.

= 1.3

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aCl Equivalent Method

3. WHITE VINCENT METHOD

Principle:
A Isotonic solution + B isotonic solution = C isotonic solution

This method involves the addition of water to medicament to obtain an isotonic solution. This
followed by the addition of isotonic buffer solution or preservatives isotonic solution to the required
volume.
V = W X E1% X 111.1
Where;
V= V (ml) of isotonic solution that could be obtain in wg of drug in water (the amount of water to added
to form isotonic solution)
W= amount of drug in the formula
E1%=NaCl equivalent of the drug
111.1= constant that could be find from volume for 1% isotonic NaCl

0.9% NaCl 1% NaCl

0.9g NaCl 100 ml
1 g NaCl 111.1 ml

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White Vincent & Sprowl Method

Example 3.1
Rx
Ephedrine HCl
Chlorobutol
NaCl
Distilled water

1g
0.5g
q.s
200ml

E 1%
0.3
0.24
isotonic

Solution;

This solution is isotonic (A)

For ephedrine HCl, V=1 X 0.3 X 111.1 = 33.33ml (final volume)

For chlorobutol, V=0.5 X 0.24 X 111.1 = 13.33ml (final volume)

So the overall
This solution is isotonic (B)
solution is isotonic

200ml (33.33 + 13.33) ml = 153.34ml

Amount of NaCl required to adjust 153.34ml to isotonic;

=

This solution is isotonic (C)

0.9 01
153.34  !" #$" = 1.38  01
100 !" #$"

4. SPROWL METHOD
Using white Vincent method but w is set to constant, 0.3
V = W X E1% X 111.1 or V = 33.33E1%

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White Vincent & Sprowl Method

5. MILIEQUIVALENT (mEq)
Definition; the gram equivalent weight of an ion is the ionic weight (the sum of atomic
weights of the element in an ion) in gram divided by the valence of that ion.
A mililequivalent is one thousandth part of the gram equivalent weight, the same figure
expressed in milligram. Table 5.1 makes this clear

Ion

Ionic weight

Sodium Na+
Potassium K+
Calcium Ca2+
Chloride Cl
Bicarbonate HCO3
Phosphate HPO4

23
39.1
40
35.5
61
96

Gram equivalent weight

"9
'$
(
)
5 '9=
23
39
20
35.5
61
48

Weight of 1mEq (mg)

23
39.1
20
35.5
61
48

Gram equivalent weight

i) For ion;
H) '*#5 '$
'$ =

"
'$
5 '9=

Example
1 Eq sodium 23/1 = 23g
1Eq chloride 35.5/1 =35.5

The weight of a salt containing 1mEq of a particular ion is obtained by dividing the
molecular weight of the salt by the valency of that ion multiply by the number of such
ion in the molecules

'$,  , "2 ! $ 9"$ 1I* "2  "
" '9# )
'$ "2 ! $
=
5 '9= "2 " # ') "2 !#9 "  $' " '9# '

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Miliequivalent (mEq)

Table 5.2 makes this clear

Ion

Salt used

M. of
the salt

Na+
Na+
Ca2+
Cl-

Sodium chloride
Sodium phosphate
Calcium chloride
Calcium chloride

58.5
358
147
147

Valency of
the ion

Number of
ion in salt

Weight of salt
containing 1mEq
of the ion

1
1
2
1

1
2
1
2

58.5mg
179.0mg
73.5mg
73.5mg

( N.B. the water of crystallization must not be ignored)

ii) For salt;
H) '*#5 '$
'$ =

'$ "2$' ! $
)'!$ "9 5 '9=

Example (monovalent)
1 Eq 58.5/1= 58.5g
Example (not monovalent)
1Eq CaCl2.H2O 147/2 =73.5

Miliequivalent (mEq) 1/1000 Gram Eq weight

Example
1mEq sodium 23mg
1mEq chloride 35.5g
1mEq NaCl 58.5 mg
1mEq CaCl2.H2O 73.5 mg

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Miliequivalent (mEq)

Conversion Equations
I.

To convert mEq/litre to mg/litre;

J I

II.

To convert mEq/litre to g/litre;

J I
1000

III.

To convert mEq/litre to %w/v;

J I
10000

The BPC includes table showing the weight s of salt that contain 1 mEq of specified ion;

Ion

Miliequivalent (mEq) mg

Salt

Mg of salt containing 1
mEq of specified ion

Na+

23.0

K+
Ca2+
Mg2+

39.1
20.0
12.5

ClHCO3HPO4-

35.5
61.0
48

Sodium chloride
Sodium bicarbonate
Potassium chloride
Calcium chloride
Magnesium sulphate
Magnesium chloride
Sodium chloride
Sodium bicarbonate
Sodium phosphate

58.5
84
74.5
73.5
123
101.5
58.5
84
179

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Miliequivalent (mEq)

Example 5.1
Calculate the quantities of salt required for the following electrolyte solution;
Sodium ion
Potassium ion
Magnesium ion
Phosphate ion (HPO4-)
Chloride ion
Water for injection, to

20 mEq
30 mEq
5 mEq
10 mEq
45 mEq
1 litre

From table 5.3:1 mEq of both potassium and chloride ion are contained in 74.5 mg of potassium
chloride.
1 mEq of both sodium and phosphate ion are contained in 179 mg of sodium phosphate.
1 mEq of both magnesium and chloride ion are contained in 101.5 mg of magnesium
chloride.
1 mEq of both sodium and chloride ion are contained in 58.5 mg of sodium chloride.
Therefore;
30 mEq of potassium ion is provided by 30 X 74.5 mg of potassium chloride which will
also supply 30 mEq of chloride ion.
10 mEq of phosphate ion is provided by 10 X 179 mg of sodium phosphate which will
also supply 10 mEq of sodium ion.
5 mEq of magnesium ion is provided by 5 X 101.5 mg of magnesium chloride which will
also supply 5 mEq of chloride ion.
There remains a deficiency of 10mEq of each sodium and chloride ions which cn be
provided by 10 X 58.5 mg of sodium chloride. The formula becomes;

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Miliequivalent (mEq)

mg

J I

Potassium chloride
Sodium phosphate
Magnesium chloride
Sodium chloride

J I
1000

mEq

K+

74.5 X 30
179.0 X 10
101.5 X 5
58.5 X 10

2.235
1.790
0.508
0.585

30

1 litre

to 1 litre

30

Water for injection, to

Na+

Mg2+

Cl-

HPO4-

30
10

10
5

10
20
55

5
10
45

10
55

The fact that cation and anion balance confirm that the formula has been worked out correctly

Example 5.2
Express the following formula as percentage w/v.
Sodium ion
Potassium -ion
Calcium ion
Chloride ion
Water for Injections, to

147 mEq
4 mEq
4 mEq
155 mEq
1 liter.

From Table 20.6 and the appropriate conversion equation, the required percentages are

Sodium Chloride
5.85 X 147 10 000 = 0.860% W/v
Potassium Chloride
74.5 X 4 10 000 = 0.030% w/v
Calcium Chloride
73.5 X 4 10 000 = 0.029% w/v
Water for injections, to
1 liter

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Miliequivalent (mEq)

Example 5.3
Prepare 500 ml of an Intravenous solution containing 70 mEq of sodium, 2 mEq of
potassium, 4 mEq of calcium and 76 mEq of chloride.
The number of milligrams of the various chlorides which contain I mEq
of the required ions is obtained from Table 20.6 and the formula becomes

Sodium Chloride
Potassium Chloride
Calcium Chloride
Water for Injections, to

70 X 58.5 1000 = 4.0Q5 g

2 X 74.5 1000 = 0.149 g
4 X 73.5 1000 = 0.294 g
500 ml

It is not unusual for students to miscalculate the amounts for this type of formula due to
failing to appreciate that mEq is a unit of weight and not an abbreviation for mEq per litre. This
leads to an incorrect halving of the final quantities in the above example.

Example 5.4
Express 0.9 per cent sodium chloride solution to mililequivalent per litre.
0.9 10000
= 154 I*/ $)'
58.5

To Convert Percentage w/v to mEq

The number of grams (C) per 100 milliliters is converted to mg/liter by multiplying by 10
000. This, divided by the weight (W) in mg of salt containing 1mEq, will give the number of
mEq/liter.
1 10000
= I*/ $')
J

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Miliequivalent (mEq)

Adjustment to Iso-osmoticity with Blood Plasma Based on Miliequivalent

The equation used is: = 310 
Where;
a = number of mililequivalent per liter of medicament present and
b = number of mililequivalent per liter of adjusting substance required

Example 5.5
Calculate the amount of sodium chloride required to adjust a solution containing 40
mEq of each potassium and chloride ion to iso-osmoticity with blood plasma.
A solution containing 40 mEq of chloride ion provide a total of 80 mEq of anion and
cation.
= 310 80
= 230
230 mEq will be provided by 115 mEq of sodium ions and 115 mEq chloride ions.
The formula of the solution will be:Potassium chloride

74.5 mg X 40 = 2.98 g

Sodium chloride

58.5 mg X 115 = 6.73 g

Water for injection, to

1 litre

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Miliequivalent (mEq)

6. MILIMOLES
In the SI, the unit for chemical quantity is mole and the term equivalent and
mililequivalent becomes absolute. Consequently the method of expressing the composition of
body and infusion fluid is changing from the mililequivalent to mole notation.
By analogy with atoms and molecules, a mole of an ion is its ionic weight in grams but
the number of moles of each of the ions of a salt in solution depends on the number of each ion
in the molecule of the salt.
It follows that the quantity of salt, in mg, containing 1 mmol of a particular ion can be
found by dividing the molecular weight of the salt by the number of that ion contained in the
salt. For example

Salt

Ion

NaCl

Na+
CICa2+
ClNa+
HP042Na+
H2P04-

CaCl2
Na2HPO4
NaH2PO4

Quantity of salt (In mg)

containing 1mmol
M.Wt /1 = 58.5
M.Wt / 1 = 58.5
M.Wt / 1 = 147
M.Wt /2 = 73.5
M.Wt /2 = 179
M.Wt /1 = 258
M.Wt /1 = 156
M.Wt /1 = 156

Conversion Equations
To convert quantities expressed in mmol per litre into weighable amounts. The
following formulae may be used: <') $)' = J M
 <') $)' = J M 1000
<')9'$
5 = J M 10000
Where W is the number of mg of salt containing 1 mmol of the required ion and M is the
number of mmol per litre

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Milimole(mmol)

Example 6.1
Calculate the quantities of salts required for the following electrolyte solution.

Sodium
Potassium
Magnesium
Calcium
Chloride
Water for injection,

60 mmol
5 mmol
4 mmol
4mmol
81 mmol
to 1 litre

From Table 20.8

5 mmol of potassium ion is provided by 5 x 745 mg of potassium
chloride which also provides 5 mmol of chloride ion.
4 mmol of magnesium ion is provided by 4 x 203 mg of magnesium chloride which also
provides 2 x 4 mmol = 8 mmol of chloride ion, since there are two chloride ions in the molecule.
4 mmol of calcium ion are provided by 4 x 147 mg of calcium chloride which, like
magnesium chloride, also provides 8 mmol of chloride ion.
60 mmol of sodium ion is provided by 60 x 58.5 mg of sodium chloride which provides a
further 60 mmol of chloride.
The formula becomes
mmol
WXM

K+ Mg2+ Ca2+ Na+ Cl-

Potassium chloride

5 x 74.5 = 0.373 g 5

Magnesium chloride

4 x 203 = 0.812 g

Calcium chloride

4 x 147 = 0.588 g

Sodium chloride

60 x 58.5 = 3.510 g

Water for injection, to

5
4

8
4

8
60

60

1 litre
73

31

Although there appears to be inequality between the anions and cations, the charges are equally
balanced.

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Milimole(mmol)

Example 6.2
Calculate the number of millimoles of (a) dextrose and (b) sodium ions in 1 litre of
Sodium Chloride and Dextrose Injection containing 4.3 per cent w/v of anhydrous dextrose and
0.18 per cent w/v of sodium chloride.
Use the conversion equation
<')9'$
5 = J M 10000
M=

<')9'$
5 10000
J

a) For dextrose
Since dextrose is non-electrolyte, W = M.Wt
Hence,
M=

4.3 10000
= 239 "
180.2

b) For sodium chloride

0.18 10000
= 31 "
58.5
Since 1 mmol sodium chloride provides 1 mmol of sodium ion and 1 mmol of chloride ion, 1 litre
of the solution will contain 31 mmol of sodium ion (and 31 mmol of chloride ion ).
M=

Example 6.3
Calculate the number of milimoles of calcium and chloride ion in a litre of a 0.029 per
cent solution of calcium chloride.
M=

0,029 10000
= 2 "
147

But, each mole of calcium chloride provides 1 mol of calcium ions and 2 moles of chloride ions.
Therefore, 1 litre of solution contains 2mmol of calcium ion and 4 mmol of chloride ion.

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Milimole(mmol)

ppm calculation
EXample
Prepare 90ml NaF solution so that 5ml of the solution when diluted with water to 1cupfull(240ml), a
3ppm solution obtained.
Solution;
5ml solution 240ml final volume
90ml solution ? ml final volume
=

(240 )(90 )
= 4329
5

3g Na 1000000ml
? ml 4320ml
=

(OG
PQ)(GPQ)


PQ

= 0.01296

0.01296mg needed 13mg NaF

Formula
NaF

13mg

Distilled water q.s ad. 90ml

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Calculation involving density factor

EXample
Given acetic acid BPC (33%w/w, d=1.04g/ml).What is the concentration of acetic acid in %w/w
Solution;
Acetic acid
33%w/w= 33g acetic acid in 100g solution
d= 1.04g/ml
? w/v

33g acetic acid 100g acid solution

33g acetic acid ?ml solution
From density factor information;
104g acid 100ml acid solution
100g acid ?ml acid solution
=

(

PQ)(

R)

OR

= 96.15 9& !" #$"

? gram acetic acid 100ml solution

=

33
100 = 34%
5
96.15

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