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Dilution, Concentration and Alligation

Dilution, Concentration and Alligation


• There are occasions in which the dilution or concentration of a pharmaceutical
preparation is either desirable or required.
• 1st quantity X 1st concentration = 2nd quantity X 2nd concentration
• Q1 X C1 = Q2 X C2

• Example(1): if 500 ml of 15% v/v solution are diluted to 1500 ml, what will be the
percentage strength (v/v)
Q1 X C1 = Q2 X C2
500(ml) X 15(%) = 1500(ml) X x(%) X = 5%

• Example(2): if 50 ml of 1: 20 w/v solution are diluted to 1000 ml, what is the ratio
strength (w/v)?
1 : 20 = 5%
Q1 X C1 = Q2 X C2
50(ml) X 5(%) = 1000(ml) X x(%) X = 0.25% = 1: 400
Altering Product Strength

• If a mixture of a given strength is diluted to twice its original quantity,


its strength will be reduced by one half because the active ingredient
will be contained in twice as many parts of the whole
• 5 grams in 100 mL = 5%
• 5 grams in 200 mL = 2.5 %
Dilution and Concentration

• If a mixture is concentrated to one half its original quantity, the active


ingredient will be contained in one-half as many parts of the whole
and the strength will be doubled.
• 5 grams in 100 mL = 5%
• 5 grams in 50 mL = 10%
• The percentage or ratio strength decreases as the quantity of
solution increases (active ingredient remains constant)
• The converse is also true
• 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 concentrations.
• Example(1): 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% and 1: 2000 = 0.05% and 4 liters = 4000 ml
• Q1 X C1 = Q2 X C2
• 4000(ml) X 0.05(%) = X (ml) X 0.25(%) X = 800 ml

• Example(2): How many milliliters of a 1:50 stock solution of phenylephrine


hydrochloride should be used in compounding the following prescription.
• R/ phenylephrine HCl 0.25%
• Rose water ad 30 ml
• Sig. For the nose
• 1 : 50 =2%
• x X 2% = 30 X 0.25% X = 3.75 ml
Dilutions and Concentrations

• Pharmaceutical Preparations may be diluted:


– by addition of diluent/solvent
– by admixture with solutions of lower strength

• Pharmaceutical Preparations may be concentrated:


– By the addition of active ingredient or
– By admixture with solutions of greater strength or
– By evaporation of the diluent/solvent
• Some calculations used in pharmacy 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.
• e.g. when the pharmacist need to prepare and dispense a concentrated solution and direct
the patient to use small volume (5 ml, teaspoonful) and dilute it in a specified volume of
water.

• Example(1): 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 solution 0.5 g : 500 ml
• 0.5 g drug in 500 ml is the same amount found in 5 ml
• 0.5 5
• X 50 X=5g
• Example(2): 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?
• 1 750
• X 300 X = 0.4 g
• 1 2500
• 0.4 X X = 1000 ml 1000 – 300 = 700 ml
Problem1

• If a 0.067% (w/v) methylbenethonium chloride lotion is diluted with


an equal volume of water, what will be the ratio strength (w/v) of the
dilution?

• Suppose we consider 100 ml of 0.067 % (w/v) solution and it is


diluted with equal amount of water , that is 100ml, then the final
volume of diluted solution will be 200 ml.
• Q1 X C1 = Q2 X C2
• 100 (ml) x 0.067 % = 200 (ml) x X%
• X = 100 x 0.067 = 0.0335 %
• 200
Problem 2

• What is the strength of a sodium chloride solution obtained by


evaporating 800 g of a 10% (w/w) solution to 250 g?

• Q1 X C1 = Q2 X C2
• 800 g x 10 % = 250 g x X%
• X = 800 x 10 = 32 %
• 250
Problem 3

• How many milliliters of water for injection must be added to 10 liters


of a 50%(w/v) dextrose injection to reduce the concentration to 30%
(w/v)

• Q1 X C1 = Q2 X C2
• 10 (L) x 50 % = x (L ) x 30 %
• x (L) = 10 x 50 = 16.66 L
30
Now , the amount of water of injection to be added will be 16.66 L – 10 L=
6.66L or 6660 ml
Problem 4
• 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

4000 ml X 0.05 = x (ml) X 0.25


X = 800 ml
Problem 5

• How many milliliters of a 1:50 (w/v) stock solution of a chemical


should be used to prepare 1 liter of a 1:4000 (w/v) solution?

• 1: 50 = 2 %
• 1:4000 = 0.025 %

• Q1 X C1 = Q2 X C2
x (ml) X 2 % = 1000 (ml) X 0.025 %
X = 12.5 ml
Problem 6

• If a syrup containing 65% (w/v) of sucrose is evaporated to 85% of


its volume, what percent (w/v) of sucrose will it contain?

Suppose we consider 100 ml of syrup


If we evaporate 100 ml of syrup to 85% of its volume, we will have 85
ml.
• Q1 X C1 = Q2 X C2
• 65% X100 (ml) = x (%) X 85 ml
• X = 76.47 %
Problem 7

How much silver nitrate 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 means 1 g of silver nitrate dissolved in 1000mlof solution

1 g in 1000ml,
X (g) in 500 ml ,

X = 0.5 g of drug in 500ml ( of diluted solution), which is also the


amount in 5 ml of the stronger solution .

5 ml of stronger solution constains 0.5 g of drug


50 ml of stronger solution will have x (g) of drug

X = 0.5 X 50 =5g
5
• Dilution of alcohol:
When water and alcohol are mixed there is a physical contraction in the resultant
volume.
• Example: How much water should be mixed with 5000 ml 85% v/v alcohol to make
50% v/v alcohol?
Q1 X C1 = Q2 X C2
5000(ml) X 85(%) = X (ml) X 50(%) X = 8500 ml
so enough water is added to make 8500 ml.
Dilution of Acids

• The strength of an official concentrated acid is expressed as


percentage weight-in-weight, e.g., HCl, NF contains 36.5% w/w
• The strength of an official diluted acid is expressed as percentage
weight-in-volume, e.g., Dil HCl, NF contains 9.5% w/v
• Example: How many mls of 37% w/w HCl having a specific gravity of
1.20 are required to make 1000 ml of dil HCl 10% w/v?
• 1000 X 0.1 = 100 gm of HCl 100% in 1000 ml of 10% w/v
Q1 X C1 = Q2 X C2
100g X 100(%) = X (ml) X 37(%) X = 270 g of 37% acid
270/1.2 = 225 ml
Problem 8

• How many milliliters of 37% (w/w) hydrochloric acid having a


specific gravity of 1.20 are required to make 1000 mL of diluted
hydrochloric acid 10% (w/v)?
• Dilution and concentration of solids and semisolids:
• Example: How many grams of opium containing 15% w/w of morphine and how
many grams of lactose should be used to prepare 150 g of opium containing 10% w/w
of morphine?
• Q1 X C1 = Q2 X C2
X g X 15(%) = 150g X 10(%) X = 100 g of 15% opium
150 g - 100g = 50 g of opium and 100 g of lactose

• Example: How many grams of 20% benzocaine ointment and how many grams of
ointment base (diluent) should be used in preparing 5 lb. of 2.5 % benzocaine
ointment?
• 5 lb = 454 g X 5 = 2270 g
Q1 X C1 = Q2 X C2
2270g X 2.5(%) = X g X 20(%) X = 283.75 or 284 g
2270 – 284 = 1986 g of ointment base
Problem 9

• If some moist crude drug contains 7.2% of active ingredient and


21.6% of water, what will be the percentage (w/w) of active
ingredient after the drug is dried?
Consider 100 g of moist crude product
In 100g , 7.2 g is active ingredient and 21.6 g is water.
Now when the crude product is dried, then the weight of crude product
Is 100 – 21.6 = 78.4 g
So , now 7.2 g of active ingredient is in 78.4 g of crude product,
So X (g) in 100 g of crude product,
X = 7.2 X 100 = 9.18 %
78.4
• Alligation
• Arithmatical method of solving problems that involves the mixing of
solutions or mixtures of solids possessing different percentage strengths.

• Alligation medial
• 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.

• Example: what is the percentage (v/v) of alcohol in a mixture of 300 ml 40% (v/v)
alcohol and 100 ml 60% (v/v) alcohol ?

Q1C1 + Q2C2 + Q3C3 +…….. = QtCt

Qt = 300+100 = 400 ml
300 X 40 + 100 X 60 = 400 X Ct
Ct = 18000/400 = 45 %
Dilution, Concentration and Alligation
Alligation
• Alligation alternate
• A method by which we may calculate the number of parts of two or more components
of a given strength when they are mixed to prepare a mixture of desired strength. A
final proportion permits us to translate relative parts to any specific denomination.

• Example: In what proportion should alcohol 95% and 55% strengths be mixed to make
70% alcohol?

• Available strength desired strength number of parts


• 95% 15 parts (95%)

• 70%

• 55% 25 parts ( 55%)


Problem 10

• In what proportion should 20% benzocaine


ointment be mixed with an ointment base
to produce a 2.5% benzocaine ointment?

• Ans: 2.5 parts of 20% ointment and


17.5 parts of ointment base(0 %)
Problem 11
• A hospital pharmacist wants to use three lots of ichthammol
ointment containing, respectively, 50%, 20%, and 5% ichthammol. In
what proportion should they be mixed to prepare a 10% ichthammol
ointment?

• Hint: The two lots containing more (50% and 20 %) than the desired
percentage may be separately linked to lot containing less (5 %)
than the desired percentage.

• Ans: 1:1:10
Problem 12

• How many milliliters of water should be added to 100 mL of a 1:125


(w/v) solution to make a solution such that 25 mL diluted to 100 mL
will yield a 1:4000 dilution?
• 1:4000 means 0.025%, that is 0.025g of drug in 100 ml of diluted
solution, which is also the same amount in 25 ml of concentretated
solution.

• So 25 ml of concentrated solution has 0.025 g of drug.

• 1:125 means 0.8 g of drug in 100ml.


• Now, if 0.025 g is in 25 ml, then
• 0.8 g is in X ml,
X = 0.8 x 25 = 800ml,
0.025
• So, amount of water to be added will be 800 – 100 = 700 ml
Problem 13
• The formula for a buffer solution contains 1.24% (w/v) of boric acid. How
many milliliters of a 5% (w/v) boric acid solution should be used to obtain
the boric acid needed in preparing 1 liter of the buffer solution?
• Q1 X C1 = Q2 X C2

• x (ml ) X 5 % = 1000 (ml) X 1.24 %


• X = 248 ml
Problem 14

• If a pharmacist adds 3 g of hydrocortisone to 60 g of a 5% (w/w)


hydrocortisone cream, what is the final percentage strength of
hydrocortisone in the product?
• 5 % w/w means 5 g of hydrocortisone in 100 g of drug,
• so x g will be in 60 g of hydrocortisone cream.

• so X = 3 g.
• That means in 60 g of 5 % (w/w) hydrocortisone cream, there is 3 g
of drug.
• Now, if pharmacist adds 3 g of hydrocortisione to this 60 g cream,
then total weight of cream will be 63 g and amount of hydrocortisone
will be a total of 6 g.
• So, there is 6 g of drug in 63 g in ointment ,
• i.e 9.52 % (w/w)
Problem 15
• Rx
Castor Oil 5.0 mL
Euresol 15.0 mL
Alcohol 85% ad 240.0 mL

How many milliliters each of 95% (v/v) alcohol and water should be
used in preparing the prescription?
• From the total volume of the prepration (240 ml), the volume of castor oil and euresol accounts for (5 +15 =
20 ml), so the remaining amount of diluent to be added is (240 – 20 = 220 ml)
• Q1 X C1 = Q2 X C2
• x (ml) X 95(%) = 220 ml X 85 (%)
• X = 196.8 ml.
• So we need to add 196.84 ml of alcohol and q.s with water to 240 ml
Problem 16

• Phenobarbital elixir contains 400 mg of phenobarbital in each 100


mL. A physician wants to increase the phenobarbital content to 30
mg per teaspoonsful and to prescribe the dose twice a day for 24
days. How many milligrams of phenobarbital should be added to the
prescribed volume of the prescription to provide the amount needed
for the dosage regimen?
• Needed strength: 30 mg per 5 ml (1 teaspoonful)
• It has to be given twice a day for 24 days, so in total the required
prescription is 240ml which should have 1440mg of drug.
so, required prescription is 1440mg/240ml

The elixir which is present is 400 mg per 100ml, which is same as


960mg in 240 ml.

So, the amount of phenobarbital that should be added : 1440 – 960 =


480 mg
Problem 17

• How many grams of hydrocortisone should be used in preparing 2 lb


of a ¼% hydrocortisone cream?
• 2 lb = 2 x 454 g = 908 g
• ¼ % = 0.25 %
• 0.25 g in 100 g
• X g in 908 g

• X = 2.27 g
Problem 18

• How many grams of silver nitrate should be used in preparing 500


mL of a solution such that 10 mL diluted to a liter will yield a 1:5000
solution?

• 1: 5000 means 1 g of drug dissolved in 5000ml,


• So, for 1000ml, x g should be dissolved.

• X = 1000/5000 = 0.2 g
• This means that 0.2 g drug should be dissolved in 1000ml, which is
also the same amount dissolved in 10 ml of stronger solution
• 10 ml of stronger solution ------ 0.2 g of drug
• 500 ml of stronger solution------- x g of drug
• X = 0.2 x 500 = 10 g
• 100
Case #1
• A pharmacist received a prescription for 100 mL of a cefuroxime axetil suspension to contain 300 mg of drug in each 5 mL.
The pharmacist has 100 mL of a suspension containing 250 mg/5 mL and also has 250-mg scored tablets of the drug. How
many tablets should be pulverized and added to the suspension to achieve the desired strength? Assume no increase in the
volume of the suspension.
• Cefuroxime axetil present in original suspenison:
• 100ml x 250mg = 5000mg
5 ml
Cefuroxime axetil required in strengthened suspension:

100 ml x 300mg = 6000mg


5 ml

Cefuroxime axetil to add : 6000mg – 5000 mg = 1000 mg

Now, 1 tablet contains 250 mg , so to add 1000 mg , we need 4x 250 , that is 4 tablets
A second Look

• The pharmacist observed that after adding the pulverized tablets, the suspension
measured 102 mL in volume. Calculations revealed that rather than the prescribed
drug strength of 300 mg/5 mL, there were 294.1 mg/5 mL. What should the
pharmacist do to bring the suspension to the desired strength?

• Cefuroxime axetil in strenghthened suspension plus another tablet:


6000mg + 250 mg = 6250 mg
Volume of suspension that could be prepared at a concentration of 300 mg /5ml:
5ml x 6250 mg = 104.17 ml
300 mg
Volume to dispense: 100 ml and volume to discard: 4.17 ml
Case #2
• Rx
Hydrocortisone 0.6%
AQUAPHOR q.s. ad 15 g
Sig: Apply to child’s affected area t.i.d.

The pharmacist has no hydrocortisone powder but does have a


hydrocortisone cream, 1%. How many grams each of hydrocortisone cream and Aquaphor should be used in filling the
prescription?

0.6% means 0.6 g in 100 g of ointment,


x g in 15 g of ointment,
X = 0.6 x 15 = 0.09 g
100
1 % hydrocortisone cream means 1 g of hydrocortisone in 100 g of ointment,
0.09 g of hydrocortisone in X g of ointment ,
X = 0.09 x 100/1 = 9 g ,
So 9 g of hydrocortisone cream and 15-9 = 6 g of Aquaphor
References:
• Pharmaceutical Calculations, 13th edition
by Howard C. Ansel.
• Dr. Mohammad Habib’s lecture notes.