Pharmaceutical

calculation
Assist.Lecturer
Qasim Allawi Bader
MSc Pharmaceutics
Specific gravity of mixtures: (continued)
Example:
How many ml.s of each of two liquids with sp. Gr. 0.95 and 0.875 should be used to prepare 1500 ml of a solution has sp.
Gr. 0.925?

Sol:
0.95 0.050 parts
0.925 1500 ml
0.875 0.025 parts

relative amount 50 : 25 or 2 : 1
2+1 = 3 total parts

1 3
X 1500 x=500 ml of 0.875 liquid
1500-500 = 1000 ml of 0.95 liquid
Example:
Rx
Zinc oxide 1.5
Hydrophilic petrolatum 2.5
Purified water 5
Hydrophilic ointment ad 30
How much zinc oxide should be added to the product to make a 10% zinc oxide ointment?
Sol:
1.5 30
X 100 x= 5%

100% 5 parts of 100%

10%
5% 90 parts of 5%
Relative amount 5 : 90 = 1: 18

1 18
X 30 x = 1.667g zinc oxide
An other way:
10% zinc oxide mean 90% conc. of diluent
30 gm – 1.5 = 28.5 gm amount of diluent which is the same amount in
the new 10% oint.

90 100
28.5 X X = 31.67 gm total wt. of the oint.

31.67 – 30 = 1.67 gm wt. of the zinc oxide should be added.

Example:
castor oil 5ml
Resorcinol monoacetate 15ml
Alcohol 85 % ad 240ml
How many ml.s each of 95% v/v alcohol and water should be used in preparing the prescription?
Sol.1:
5+15 = 20 ml of cast. Oil. And resorcinol.
240 -20 = 220 ml of 85% alcohol

85% 100
X 220 x = 187 ml

95 100
187 y y = 196.84 ml of 95% alcohol.

.
Sol.2:

C1 V1 = C2 V2
85 * 220 = 95 * V2
V2 = 196.84 ml of 95% alcohol
Water: add water enough to make 220 ml of 85% alcohol
Example:
Benzalkonium chloride sol. 240 ml.
Make a solution such that 10 ml diluted to a liter equals a 1:5000 solution.
How many milliliters of a 17% stock solution of Benzalkonium chloride should be used in preparing the
prescription ?
Sol:
1 5000
X 1000 x = 0.2 g in liter and the same in 10 ml.s

0.2 10
Y 240 y = 4.8 gm in 240 ml

17 100
4.8 Z Z = 28.2 ml stock solution.
Example:
How many ml.s of a 2.5 % w/v chlorpromazine hydrochloride injection
and how many ml.s of 0.9% w/v sodium chloride should be used to
prepare 500 ml of a 0.3% w/v chlorpromazine hydrochloride injection?
Sol:
C1 V1 = C2 V2
2.5 * V1 = 0.3 * 500
V1 = 60 ml of chlorpromazine.
500 – 60 = 440 ml of sodium chloride.

(H.W: answer this ex. With alligation alternate method. )

Isotonic solution
• When a solvent passes through a semipermeable membrane from a dilute solution in to a more
concentrated one, the concentrations become equalized and the phenomenon is known as osmosis.
• Thus, osmotic pressure is the pressure responsible for this phenomenon which varies with the
nature of the solute.
We have two type of solute:
1. Nonelectrolyte, its solution contains only molecules and the osmotic pressure depends on the
conc. of the solute.

2. electrolyte solution , its solution contains ions and the osmotic pressure depends on the conc. of
the solute and its degree of dissociation.
Thus , solutes that dissociate present a greater no. of particles in solution and exert a greater osmotic
pressure than undissociated molecules
• Colligative properties; such as osmotic pressure, vapor pressure,
boiling point, and freezing point depend on the no. of particles in
solution therefore the change in any one of them will result in a
change in the other.
• Isosmotic solutions: they are two solutions have the same osmotic
pressure.
• Isotonic solution: a solution have the same osmotic pressure as body
fluid ( serum, lacrimal fluid).
• Hypotonic solution: a solution have lower osmotic pressure than that
of a body fluid.
• Hypertonic solution: a solution have higher osmotic pressure than
that of a body fluid
• Most ophthalmic preparations should be isotonic or approximately
isotonic to be comfort to the patient and to reduce the irritation of the
eyes.
• Injections that are not isotonic should be administered slowly and in
small quantities to minimize tissue irritation and pain.
• Intravenous infusions which are hypotonic or hypertonic can have
adverse effects because they generally are administered in large
volumes.
• We can calculate the osmotic pressure depending on colligative
properties especially freezing point.
• Note: freezing point of both serum and lacrimal fluid is (- 0.52 ◦C)
• Freezing point (or any other colligative properties) of solutions could
be used for determining the tonicity of these solutions.
• As we said before F.P. of body fluid is (-0.52 ◦c) so, any substance
has this F.P. should be isotonic with body fluid.
Calculation of tonicity for nonelectrolyte
substances
• When one gram molecular weight of any nonelectrolyte is dissolved in
1000 gm of water, the freezing point of the solution is about (-1.86
C)
• So we can calculate the weight of substance that should be dissolved
in (1000 gm) of water
Example: Boric acid has m.wt = 61.8 , thus 61.8 gm when dissolved in
1000 gm of water should produce F.P. = - 1.86 ◦c therefore:
1.86/0.52=61.8g/x
X=17.3 gm of boric acid in 1000 gm of water = 1.73% (w/v) make
isotonic sol.
Calculation of tonicity for electrolyte substances:

• Here osmotic pressure depend on the degree of dissociation.

• Example: Sodium chloride in weak solution 80% dissociated ( and have m.wt. =
58.5) so, 100 molecules give 180 molecules
Dissociation factor (i) = 180/100 = 1.8 therefore: simple isotonic solution could
be calculated as follow:
0.52 * m.wt. /1.86 * (i) = ( ) gm of solute in 1000 gm water.
X= 9.09 gm of NaCl in 1000 gm of water = 0.9% (w/v) make isotonic sol
• If the no. of dissociated ions is known , (i) could be determined:
(i)
• non electrolyte substances 1
• substances that dissociate in to 2 ions 1.8
• substances that dissociate in to 3 ions 2.6
• substances that dissociate in to 4 ions 3.4
• substances that dissociate in to 5 ions 4.2
Example
How much Sod. Chloride should be added to 0.5% w/v sol. to make it
isotonic ?
0.5% 0.5 gm /100 ml water
0.9% 0.9 gm/ 100 ml water Then
0.9 – 0.5 = 0.4 gm of NaCl should be added to 100 ml 0.5% sol. to be
made isotonic with body fluid.
• Sodium chloride equivalent (E value): is the no. of gm.s of NaCl which
is equivalent to 1 gm of the substance.

• E value = m.wt of NaCl / (i) of NaCl * (i) of the sub / m.wt of the
sub.
Ex.
 Calculation of Sodium Chloride
equivalent (E values)
• Papavarine HCl (M.wt = 376) is a 2-ion electrolyte dissociating 80%.
Calculate its E-value, where its dissociation factor (i) = 1.8

M.Wt of NaCl = 58.5

By substituting the values in the equation:
E = 58.5/1.8 X 1.8/376 = 0.156 or 0.16
Ex.
• How much NaCl should be used in preparing 100 ml of a 1% w/v solution of Atropine sulfate, which
should be made isotonic?
‫الجواب هنا يعتمد على حساب كمية والتي تكافئ‬
NaCl Atropine sulfate
m.wt of NaCl = 58.5 , i = 1.8
m.wt of Atropine sulfate = 695 , i = 2.6
1% w/v 1gm in 100 ml

X = 0.12 gm of NaCl represented by 1 gm of Atropine sulfate ( E value )

0.9 – 0.12 = 0.78 gm of NaCl should be added to 100 ml 1% w/v Atropine sulfate sol. to make it
isotonic.
• Example:
• Calculate the dis. factor of zinc sulfate (2 ion electrolyte, dissociating 40 %) ?

100 particle will give : 40 zinc ions

40 sulfate ions
60 undissociated particles
140 particles
So, dissociation factor (i) = 140/100 = 1.4 , answer.
Example:
Calculate the dissociation factor of zinc chloride ( 3 ion electrolyte , dissociating 80 %)

100 particle will give : 80 zinc ions

80 chloride ions
80 chloride ions
20 undissociated particles
260 particles
So, dissociation factor (i) = 260/100 = 2.6 answer.
The amount of NaCl represented by a sub. = wt. of the sub. * E value

The procedure for calculating isotonic sol. With NaCl equivalent is:
1. Calculate the amount of NaCl represented by the sub. In the prescription
(sub. amount * E value).
2. Calculate the amount of NaCl that would be contained in a 0.9% solution of the volume of
the prescription.
3. Amount of NaCl added to make the sol. Isotonic =Amount of NaCl (step 2) – amount of
NaCl (step 1)
4. If an agent other than NaCl ( Boric acid, dextrose …) is to be used to make isotonic
solution , we will divide the amount of NaCl (step 3) by the E value of that agent.
Example:
how many grams of sodium chloride should be used in compounding the
following prescription? (E value of Pilocarpine nitrate is 0.23)
Rx
Pilocarpine nitrate 0.3
Sodium chloride q.s.
Purified water ad 30 ml
Make isoton. Sol.
Sig. for the eye
Example:

How many grams of Boric acid should be used in compounding the following prescreptioin?
(E value of Phenacaine Hydrochloride is 0.20 and E value of Chlorobutanol is 0.24)

Rx
Phenacaine Hydrochloride 1%
Chlorobutanol ½%
Boric acid q.s.
Purified water ad 60
Make isoton. Sol.
1gm 100ml 0.5gm 100ml
X 60ml X = 0.6gm X 60ml X= 0.3gm

So, the prescription calls for 0.6 g of Phenacaine Hydrochloride and 0.3 g of Chlorobutanol.
Step 1.
0.20 * 0.6 g = 0.120 g of NaCl represented by Phenacaine Hydrochloride
0.24* 0.3 g = 0.072 g of NaCl represented by Chlorobutanol.

Total 0.192 g of NaCl represented by both ingredients.

Step2.
60* 0.009 = 0.540 g of NaCl in 60 ml of an isotonic NaCl sol.
Step3.
0.540 g (from step2)
- 0.192g (from step1)

0.348 g of NaCl required to make the sol. Isotonic.

But because the prescription calls for boric acid:

Step4.
0.348 g / 0.52 (E value of Boric acid) = 0.669 g of Boric acid to be used.
Using an isotonic sodium chloride solution
to prepare other isotonic solution
0.9% w/v NaCl solution used to compound isotonic solutions of other substances as follow:

Step.1: Calculate the quantity of the drug needed in the prescription.

Step 2: Calculate the volume of water needed to make the solution isotonic:

gm(drug) * E value(drug)
= ( ) ml of water needed to make isotonic of the drug
0.009

Step.3: Add 0.9% w/v NaCl solution to complete the volume of the prescription.
Example:

what is the volume of water and 0.9% w/v NaCl solution needed to prepare 20 ml of a 1% w/v solution of hydromorphone
hydrochloride ( E- value =0.22)

Answer:

step.1:
1 100
X 20 X= 0.2 gm hydromorphone.

Step.2:

0.2 gm * 0.22 = 4.89 ml water required to make isotonic solution of hydromorphone

0.009.
Step.3:

20 - 4.89 = 15.11 ml of 0.9% w/v NaCl solution required

• Example:
Tetracaine Hcl 0.5%
Epinephrine Bitartarate 1:1000 10
Boric acid q.s.
Purified water 30
Make isotonic sol.
The solution of epinephrine is already isotonic and the E- value of
tetracaine = 0.18 How much boric acid used?
Answer:

0.5 100
X 30 X= 0.15 gm of tetracaine in the prescription

0.15 × 0.18 = 0.027 gm of NaCl represented by the sub.

30 – 10 = 20 ml
(vol. of epinephrine which is isotonic)

0.9 100
X 20 X= 0.18 gm of NaCl in 20 ml of an isotonic NaCl sol.
0.18 – 0.027 = 0.153 gm of NaCl should be added.

But here we use Boric acid , so :

0.153 ÷ 0.52 = 0.29 gm of boric acid used.

(E-value) of Boric acid
Use of freezing point in calculation of isotonicity:

Substance to be isotonic should lower freezing point ∆Tf = - o.52

(which is the freezing point of blood and lacrimal fluid).

Example:
How many milligrams each of NaCl and dibucaine HCl are required to
prepare 30 ml of 1% dibucaine HCl isotonic solution?
( ∆Tf (1% dibucaine) = - 0.08 , ∆Tf (1% NaCl) = - 0.58 )
Practice problems of isotonic
solution
EX.
• 1. How many grams each of lidocaine hydrochloride (i) and sodium
chloride (ii) are required to prepare 150ml of a 2% w/v solution of
lidocaine hydrochloride isotonic with blood plasma? Freezing point
depression of a 1% w/v lidocaine hydrochloride solution is 0.063◦C
and that of sodium chloride is 0.576◦C.
• 2. A pharmacist receives a prescription for 10ml of isotonic 1% w/v
atropine sulfate eye drops. What weight of sodium chloride is
required to make the solution isotonic with tears?

• 1. (i) 3g (ii) 1.026g

• 2. 78.125mg
Home works
1.How many grams of NaCl and Naphazoline HCl should be used in
compounding the following prescription:
Rx
Naphazoline HCl 1%
NaCl Q.S.
Purified water ad 30ml
Make isotonic solution.
Use the freezing point depression method.
Tf blood = 0.52
Tf 1% NaCl = 0.58
Tf 1% Naphazoline HCl = 0.16
2.For agent having 0.32 sodium chloride equivalent, calculate the
percentage concentration of an isotonic solution.
3.Calculate the E value for holocaine hydrochloride, if 6.7 mL of water
will produce an isotonic solution from 0.3 g of drug substance.
4.The freezing point of 5% solution of boric acid is -1.55 oC. How many
grams of boric acid should be used in preparing 1500 mL of an isotonic
solution?
Rx
Dextrose, anhydrous 2.5%
Sodium chloride q.s
Sterile water for injection ad 1200mL
Label: Isotonic Dextrose and Saline Solution.
How many grams of sodium chloride should be used in preparing the
solution?