AL-Mustaqbal university

College of Pharmacy

Pharmaceutical calculation
Dilution and concentration of pharmaceutical preparation
lec1
The strength of a pharmaceutical preparation may be
increased or decreased by changing the proportion of active
ingredient to the whole.

• A preparation may be strengthened or made more concentrated by

the addition of active ingredient, by admixture with a like
preparation of greater strength, or through the evaporation of its
vehicle, if liquid.

• The strength of a preparation may be decreased or diluted by the

addition of diluent or by admixture with a like preparation of lesser
strength.
The dilution of a liquid dosage form, as a solution or suspension,
may be desired to provide a product strength more suitable for use
by a particular patient (e.g., pediatric, elderly, those in disease
states)

The diluent is selected based on its compatibility with the vehicle

of the original product; that is, aqueous, alcoholic, hydroalcoholic,
or other .

The dilution of a solid dosage form (as a powder or the contents of a

capsule) or a semisolid dosage form (as an ointment or cream) also
may be performed to alter the dose or strength of a product .
The concentration of a liquid preparation, as through the
evaporation of a portion of its solvent or vehicle, rarely is performed
nowadays.

However, the fortification of a liquid, solid, or semisolid dosage

form, by the addition of a calculated quantity of additional
therapeutic agent, remains a viable practice in pharmacy
compounding
If a mixture of a given percentage or ratio strength is diluted to twice its original
quantity, its active ingredient will be contained in twice as many parts of the whole,
and its strength therefore will be reduced by one half .

By contrast, if a mixture is concentrated by evaporation to one-half its original

quantity, the active ingredient (assuming that none was lost by evaporation) will be
contained in one half as many parts of the whole, and the strength will be doubled

.
so, if 50 mL of a solution containing 10 g of active ingredient with a strength of 20%
or 1:5 w/v are diluted to 100 mL, the original volume is doubled, but the original
strength is now reduced by one half to 10% or 1:10 w/v. If, by evaporation of the
solvent, the volume of the solution is reduced to 25 mL or one half the original
quantity, the 10 g of the active ingredient will indicate a strength of 40% or 1:2.5
w/v.
The percentage or ratio strength (concentration) of a component in a
pharmaceutical preparation is based on its quantity relative to the total
quantity of the preparation .

If the quantity of the component remains constant, any change in the

total quantity of the preparation, through dilution or concentration,
changes the concentration of the component in the preparation
inversely. An equation useful in these calculations is
1st quantity x 1st concentration =(2nd quantity)x(2nd concentration)
or Q1 x C1 = Q2 x C2
Example Calculations of the Dilution and Concentration of Liquids
If 500 mL of a 15% v/v solution are diluted to 1500 mL, what will be
the percentage strength (v/v?)
If 50 mL of a 1:20 w/v solution are diluted to 1000 mL, what is
the ratio strength (w/v?)
Note: A student may find it simpler in solving certain problems
to convert a given ratio strength to its equivalent percentage
strength
How many milliliters of a 1:5000 w/v solution of the preservative
auralkonium chloride can be made from 125 mL of a 0.2% solution?

1/5000 x 100 % = 0.02 %

V1 C1 = V2 C2

125 (mL) x 0.2 (%) = X (mL) x 0.02 (%)

X= 1250 mL,
Strengthening of a Pharmaceutical Product
The addition of active ingredient or by the admixture with a calculated
quantity of a like-product of greater concentration
example calculations of product strengthening
 If a cough syrup contains in each teaspoonful, 1 mg of
chlorpheniramine maleate and if a pharmacist desired to double
the strength, how many milligrams of that ingredient would need
to be added to a 60-mL container of the syrup. Assume no
increase in volume
 Stock Solutions
Stock solutions are concentrated solutions of active (e.g., drug) or
inactive (e.g., colorant) substances and are used by pharmacists as a
convenience to prepare solutions of lesser concentration
Example Calculations of Stock Solutions
How many milliliters of a 1:400 w/v stock solution should be
used to make 4 liters of a 1:2000 w/v solution?

4 liters = 4000 ml
1/400 x 100 % = 0.25 %
1/2000 x 100 % = 0.05 %

V1 C1 = V2 C2
4000 ml * 0.05 % = X ml * 0.25 %
X= 800 ml
How many milliliters of a 1% stock solution of a certified red dye
should be used in preparing 4000 mL of a mouthwash that is to
contain 1:20,000 w/v of the certified red dye as a coloring agent?1

1:20000 x 100% = 0.005%

V1 C1 = V2 C2
1% x X(ml) = 4000(ml) x 0.005%

X= 20 ml
How many milliliters of a 1:50 stock solution of phenylephrine
hydrochloride should be used in compounding the following
prescription?
How many milliliters of water should be added to a pint of a 5% w/v
solution to make a 2% w/v solution?

1 pint = 473ml

C1 V1 = C2 V2

473 ml x 5% = (X)ml x 2%

X= 1182.5 ml
and 1182.5 ml – 473 ml = 709.5 ml
How many milliliters of water should be added to 375 mL of a
solution containing 0.5 g of benzalkonium chloride to make a 1:5000
solution?

1 / 5000 x 100% = 0.02 %

0.5 / 375 x 100% = 0.133 %

C1 V1 = C2 V2
375ml x 0.133% = V2ml x 0.02%
V2 = 2500
2500ml – 375ml = 2125 ml
If 15 mL of a 0.06% ATROVENT (ipratropium bromide) nasal
spray were diluted with 6 mL of normal saline solution, what would
be the final drug concentration?

V2 = 15 ml + 6ml = 21 ml

.
 Dilution of alcohol

When water and alcohol are mixed, there is a physical contraction such
that the resultant volume is less than the total of the individual
volumes of the two liquids .

Thus, to prepare a volume-in volume strength of an alcohol dilution,

the alcohol ‘‘solute’’ may be determined and water used to ‘ q.s.’’ to
the appropriate volume .

Because the contraction of the liquids does not affect the weights of
the components, the weight of water (and from this, the volume)
needed to dilute alcohol to a desired weight-in-weight strength may be
calculated
How much water should be added to 4000 g of 90% w/w alcohol
to make 40% w/w alcohol?

V1 C1 = V2 C2
X(g) x 40% = 4000g x 90%
X= 9000 g
9000g – 4000g = 5000 g = 5000 ml
How many milliliters of 95% v/v alcohol and how much water
should be used in compounding the following prescription?

Therefore, use 22.1 mL of 95% v/v alcohol and enough water to

make 30 mL, answer.
 Dilution of acids
The strength of an official undiluted (concentrated) acid is expressed as
percentage weight-in weight. For example, Hydrochloric Acid, NF,
contains not less than 36.5% and not more than 38.0%, by weight, of
HCl .
However, the strength of an official diluted acid is expressed as
percentage weight-in-volume. For example, Diluted Hydrochloric
Acid, NF, contains, in each 100 mL, not less than 9.5 g and not more
than 10.5 g of HCl .

It is necessary, therefore, to consider the specific gravity of

concentrated acids in calculating the volume to be used in preparing a
desired quantity of a diluted acid
 How many milliliters of 85% w/w phosphoric acid having a
specific gravity of 1.71 should be used in preparing 1 gallon of
1⁄4% w/v phosphoric acid solution to be used for bladder
irrigation?

¼ x 100 % = 0.25%
1 gallon = 3785 ml
V1 C1 = V2 C2
X ml x 85% = 3785 ml x 0.25%
X= 11.13 ml
11.3 ml / 1.71 = 6.5 ml
 Dilution and Fortification of Solids and Semisolids

The dilution of solids in pharmacy occurs when there is need to

achieve a lower concentration of an active component in a more
concentrated preparation (e.g., a powdered vegetable drug)
Example Calculations of Solid and Semisolid Dilutions
If 30 g of a 1% hydrocortisone ointment were diluted with 12 g of
Vaseline, what would be the concentration of hydrocortisone in the
mixture?

V2 = 30 g + 12 g = 42 g

30 (g) 1 (%) = 42 (g) x (%)

X= 0.71% (w/w), answer.
 Trituration
There also is a type of diluted pharmaceutical preparation, termed a
Trituration (are dilutions of potent medicinal substances. They were
at one time official and were prepared by diluting one part by weight
of the drug with nine parts of finely powdered lactose. They are,
therefore, 10% or 1:10 w/w mixtures).

Reducing or enhancing the strengths of creams and ointments is a

usual part of a compounding pharmacist’s practice to meet the
special needs of patients.

The dilution of semisolids is a usual part of a compounding

pharmacist’s practice in reducing the strengths of creams and
ointments to meet the special needs of patients
How many milliliters of an injection prepared by dissolving 100 mg
of a 1:10 trituration of mechlorethamine hydrochloride in sufficient
water for injection to prepare 10 mL of injection is required to obtain
5 mg of drug?

100 mg of trituration = 10 mg of drug

10 mg of drug in 10 mL of injection
V1 C1 = V2 C2
10(ml) x 5 (mg) = X(ml) x 10 (mg)
x = 5 mL, answer.
 Alligation
Alligation is an arithmetical method of solving problems that involves the mixing
of solutions or mixtures of solids possessing different percentage strengths.

Alligation Medial. Alligation medial is a method by which the ‘‘weighted

average’’ percentage strength of a mixture of two or more substances of known
quantity and concentration may be easily calculated.

C1 * V1 = X1
C2 * V2 = X2 Alligation Medial = Total X / Total V x100%
C2 * V3 = X3
What is the percentage strength (v/v) of alcohol in a mixture of
3000 mL of 40% v/v alcohol, 1000
mL of 60% v/v alcohol, and 1000 mL of 70% v/v alcohol?
Assume no contraction of volume after
mixing.
0.40 x 3000 mL = 1200 mL
0.60 x 1000 mL = 600 mL
0.70 x 1000 mL = 700 mL
---------------- ------------
Totals: 5000 mL 2500 mL
2500 (mL) / 5000 (mL) = 0.50 x 100% = 50%, answer.
In some problems, the addition of a solvent or vehicle must be considered. It
is generally best to consider the diluent as of zero percentage strength, as
in the following problem.

What is the percentage strength of alcohol in a mixture of 500 mL of a solution

containing 40% v/v alcohol, 400 mL of a second solution containing 21% v/v
alcohol, and a sufficient quantity of a nonalcoholic third solution to make a total of
1000 mL?
0.40 x 500 mL = 200 mL
0.21 x 400 mL = 84 mL
0 x 100 mL = 0 mL
------------------ -----------
Totals: 1000 mL = 284 mL
284 (mL) / 1000 (mL) = 0.284 x 100 % = 28.4%, answer.
Alligation alternate is a method by which we may calculate
the number of parts of two or more components of a given
strength when they are to be mixed to prepare a mixture of
desired strength. A final proportion permits us to translate
relative parts to any specific denomination.