Altering product strength, use of

stock solutions, and problem

solving by allegation

by
Ali Khidher Alobaidy
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.
 Special considerations of altering product strength in
pharmaceutical compounding

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).Thediluentisselectedbasedonitscompatibilitywithth
evehicleoftheoriginal 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.
Relationship between strength and total quantity

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.
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.
If, then, the amount of active ingredient remains constant, any
change in the quantity of a solution or mixture of solids is
inversely proportional to the percentage or ratio strength; that is,
the percentage or ratio strength decreases as the quantity increases,
and conversely. This relationship is generally true for all mixtures
except solutions containing components that contract when mixed
together. Problems in this section generally may be solved by any
of the following methods:
1. Inverse proportion.
2. The equation: (1st quantity) x (1st concentration) = (2nd
quantity) x (2nd concentration), or Q1 x C1 = Q2 x C2.
 3. By determining the quantity of active ingredient (solute)
present or required and relating that quantity to the known or
desired quantity of the preparation.
 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)?
1. (inverse proportion)
1500 ml 15%
500 ml x%
X = 5%
2. Equation
Q1 (quantity) x C1 (concentration) = Q2 (quantity) x C2 (concentration)

500 (mL) x 15 (%) = 1500 (mL) x x%

X = 5%
3. By determining the quantity of active ingredient (solute) present or required.
 
500 x o.15 = 75
 
1500 ml 100%
75ml x%
X = 5%
 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.
1 20
X 100
X = 1:20 = 5%
Q1 (quantity) x C1 (concentration) = Q2 (quantity) x C2 (concentration)

50 (mL) x5 (%) = 1000 (mL) xx (%) = 0.25% = 1:400 →

 
0.25 100
1 x
X = 100 ÷ 0.25 = 400
 If a syrup containing 65% w/v of sucrose is evaporated
to 85% of its volume, what percentage (w/v) of sucrose
will it contain?
Any convenient amount of the syrup, for example, 100
mL, may be used in the calculation. If we evaporate 100
mL of the syrup to 85% of its volume, we will have 85
mL.
 C1 x V1 = C2 x V2

 100% x 65ml = C x 85ml

2

 C2 = 76.47%
 How many grams of 10% w/w ammonia solution can
be made from 1800 g of 28% w/w strong ammonia
solution?
 Q1 xC1 = Q2 x C2

 1800 (g) X28 (%) = x (g) X10% = 5040 g

 How many milliliters of a 1:5000 w/v solution of the
preservative lauralkonium chloride can be made from
125 mL of a 0.2% solution?

1:5000 = 0.02%
125 (mL) x 0.2 (%) = x (mL) x 0.02 (%)
x = 1250 mL
 If 1 gallon of a 30% w/v solution is to be evaporated
so that the solution will have a strength of 50% w/v,
what will be its volume in milliliters?

1 gallon = 3785 mL
30 % x 3785 = 50% x v2
V2 = 2271ml
 Strengthening of pharmaceutical product

 As noted previously, there is occasion in which a

pharmacist may be called upon to strengthen an
existing pharmaceutical product. This may be
accomplished by the addition of active ingredient or
by the admixture with a calculated quantity of a like-
product of greater concentration.
 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?
1mg 5ml
X 60ml
 X = 12mg chlorpheniramine maleate in original syrup.

 To double the strength, 12 mg of additional

chlorpheniramine maleate would be required.

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.
 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?
 1: 400 = 0.25%

 1: 2000 = 0.05%

 Q1 x C1 = Q2 x C2

 0.05% x 4000 = Q2 x 0.25%

 Q2 = 800 ml
 How many milliliters of a 1:400 w/v stock solution
should be used in preparing 1 gallon of a 1:2000 w/v
solution?
 1 gallon = 3785 mL

 1: 400 = 0.25%

 1: 2000 = 0.05%

 Q1 x C1 = Q2 x C2

 3785 x 0.05 = Q2 x 0.25

 Q2 = 757ml
 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: 20,000 = 0.005%

 Q1 x C1 = Q2 x C2

 4000 x 0.005 = Q2 x 1

 Q2 = 20ml
 How many milliliters of a 1:16 solution of sodium
hypochlorite should be used in preparing 5000 mL of a
0.5% solution of sodium hypochlorite for irrigation?
 1:16 = 6.25%

 Q1 x C1 = Q2 x C2

 5000 x 0.5 = 6.25 x Q2

 Q2 = 400ml
 How many milliliters of a 1:50 stock solution of
phenylephrine hydrochloride should be used in
compounding the following prescription?
Rx.
Phenylephrine HCl 0.25%
Rose Water ad 30 mL
Sig. For the nose.
 1: 50 = 2%

 Q1 x C1 = Q2 x C2

 30 x 0.25% = Q2 x 2%

 Q2 = 3.75ml
 Some interesting calculations are used in pharmacy practice
in which the strength of a diluted portion of a solution is
defined, but the strength of the concentrated stock solution
used to prepare it must be determined. The relevance to
pharmacy practice may be explained, for example, by the
need of a pharmacist to prepare and dispense a concentrated
solution of a drug and direct the patient to use a specific
household measure of a solution (e.g., 1 teaspoonful) in a
specified volume of water (e.g., a pint) to make of solution
of the desired concentration (e.g., for irrigation or soaking).
This permits the dispensing of a relatively small volume of
liquid, enabling a patient to prepare relatively large volumes
as needed, rather than carrying home gallons of a diluted
solution from a pharmacy.
  How much drug should be used in preparing 50 mL of
a solution such that 5 mL diluted to 500 mL will yield
a 1: 1000 solution?
1 1000
X 500
X = 0.5g
0.5 5ml
X 50ml
X = 5g
How many grams of sodium chloride should be used in
preparing 500 mL of a stock solution such that 50 mL
diluted to 1000 mL will yield a ‘‘1⁄3 normal saline’’ (0.3%
w/v) for irrigation?
0.3g 100ml
X 1000ml
X = 3g
50 ml 3g
500ml x
X = 30g
How many milliliters ofa 17% w/v concentrate of benzalkonium chloride should be used
in preparing 300 mL of a stock solution such that 15 mL diluted to 1 liter will yield a 1 :
5000 solution?
1 liter = 1000 mL
1 : 5000 means 1 g of benzalkonium chloride in 5000 mL of solution
1g 5000ml
X 1000ml
X = 0.2g of benzalkonium chloride in 1000 mL of diluted solution (15000), which is
also the amount in 15 mL of the stronger (stock) solution to be prepared, and:
0.2g 15ml
X 300ml
X = 4g of benzalkonium chloride needed.
because a 17% w/v concentrate contains 17 g per 100 mL, then:
17g 100ml
 4g x
X = 23.5ml 
A solution of known volume and strength may be diluted
with water to prepare a solution of lesser strength. In such
calculations, first calculate the quantity of diluted solution
that may be prepared from the concentrated solution.
Then, subtract the volume of the concentrated solution
from the total quantity that may be prepared to determine
the volume of water needed.
How many milliliters of water should be added to 300 mL of a 1:750 w/v
solution of benzalkonium chloride to make a 1:2500 w/v solution?
1g 750ml
X 300ml
X = 0.4g
300 mL of a 1:750 (w/v) solution contains 0.4 g of benzalkonium chloride.
1g 2500ml
0.4g x
X = 1000 ml
The difference between the volume of diluted (weaker) solution prepared
and the volume of stronger solution used represents the volume of water
(diluent) to be used.
1000 mL - 300 mL = 700 mL
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 = 473 mL
5g 100ml
X 473ml
X = 23.65g
2g 100ml
23.65g x
X = 1182.5 ml
1182.5 ml – 473 = 709.5 ml
If the quantity of a component is given rather than the
strength of a solution, the solution may be diluted to a
desired strength as shown by the following example.
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?
1g 5000ml
0.5g X
X = 2500 ml of 1:5000 (w/v) solution containing 0.5 g of
benzalkonium chloride.
2500 mL - 375 mL = 2125 mL
If15 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?
15 mL x 0.06% = 0.009 g of ipratropium bromide
15 mL + 6 mL= 21 mL, new total volume
0.009g 21ml
X 100ml
X = 0.043%
 Allegation

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.
By this method, the percentage strength of each component, expressed as
a decimal fraction, is multiplied by its corresponding quantity; then the
sum of the products is divided by the total quantity of the mixture; and
the resultant decimal fraction is multiplied by 100 to give the percentage
strength of the mixture. Of course, the quantities must be expressed in a
common denomination, whether of weight or volume.
Example Calculations Using Alligation Medial

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%
What is the percentage of zinc oxide in an ointment
prepared by mixing 200 g of 10% ointment, 50 g of 20%
ointment, and 100 g of 5% ointment?
0.10 x 200 g = 20 g
0.20 x 50 g = 10 g
0.05 x 100 g = 5g
--------------------------------

Totals: 350 g 35 g
35 (g) ÷ 350 (g) = 0.10 x 100 = 10%
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
0.21x 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%