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DILUTION,

CONCENTRATION, AND
ALLIGATION
PMY 211
BY
Lt Jackson Yamvwa
Definitions
• Diluent
• A substance that is added to a pharmaceutical
product to reduce the strength of the product. A
diluent most often has no drug substance in it, sterile
water and petrolatum for example.
• Stock Solution
• Concentrated solutions of active or inactive
ingredients from which dilute solutions are
conveniently prepared.
Rules to Consider
• These two rules, wherever they may be applied,
greatly simplify the calculation:

I. When ratio strengths are given, convert them to


percentages.them
II. Whenever proportional parts enter into a reduce them
to their lowest terms. , reduce them to lowest terms
Relationship Between Strength and Total
Quantity
• If 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.

• This means that, as the volume increases the strength decreases.


Mass: Constant
Concentration (Ratio strength or Percentage Strength): Decrease and vice versa
Volume: Increase

• This relationship is true for all mixtures except volume-in-volume and weight-
in-volume solutions containing components that contract when mixed.
Relationship Between Strength and Total
Quantity
• Problems relating to this type of relationship are generally solved by
any of the following three methods.
i. Inverse proportion
ii. The equation C1 x Q1 = C2 x Q2
iii. By determining the quantity of active constituent (solute) needed
and then calculating the quantity of the available solution (usually
concentrated or stock solution) that will provide the needed
amount of constituent
Which Method to Use?

• For most problems, the equation (#2) is the easiest to use

• In some situations, when using vials or ampoules as your stock


product, #3 would be the best method.
Dilution and Concentration of Liquids
• Example
• If 500 mL of a 15% (v/v) solution of methyl salicylate in alcohol are diluted to
1500 mL, what will be the percentage strength (v/v)?

Q1 x C1 = Q2 x C2
500 mL (15 %) = (1500 mL) (X %)
X = 5% (answer)
Inverse Proportion Method
500ml X%
500mL X 15%
X = = 5% (v/v)
1500ml 15% 1500ml
• Method 3

15 X 500 = 75 mL
100

75 mL X
100 = 5% v/v
1500 mL
Dilution and Concentration of Liquids
• If 50 mL of a 1:20 (w/v) solution of Aluminium acetate are diluted to
1000 mL, what is the ratio strength (w/v)?
• Solutions
1 X 100 = 5% w/v
• Convert ratio strength to percentage strength: 20
Inverse Proportion method
50mL X%
1000mL 5%
50 x 5 0.25 100 1 : 400 answer
X = = 0.25% =
1000 0.25 0.25
• Formula method
Q1 x C1 = Q2 x C2

(50 mL) (5 %) = 1000 mL (X %)


X = 0.25%
= 1:400 (answer)
• Amount of Solute Present Method
1. Covert 1:20 to percentage

1:20 = X 1100 = 5%
20
2. Calculate the amount of solute present in the solution
5
2.5 g
100 X 50 =
3. Find the proportion
2.5 g = 1000 mL 1000
X = 2.5 = 400 1 : 400 (answer)
1 X
• If a syrup containing 65% w/v of sucrose is evaporated to 85% of its
initial volume, what percentage (w/v) of sucrose will it contain?
• Note:
• Any convenient amount of the syrup, e.g. 100ml, may be used in the
calculation.
• If we evaporate 100ml of the syrup to 85% of its volume, we will have
85mL.
85 (mL) 65 (%)
100 (mL) = X (%)
X = 76.47 %
• How many grams of 10% w/w ammonia solution can be made from
1800 g of 28% w/w strong ammonia solution?
• Inverse Proportion Method
1800 (g) - 28 (%)
X = 5040 g
X (g) - 10 (%)
1800 (g) x 28 (%)
• Formula Method C1Q1 = C2Q2 Q2 = 10 (%) = 5040 g
• Amount of Solute Method
10 (%) = 504 (g)
X = 5040 g
100 (%) = X (g)
Practice Questions
• How many millilitres of a 1:5000 w/v solution of the preservative
lauralkonium chloride can be made from 125 mL of a 0.2% solution?

• 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
millilitres?
STOCK SOLUTIONS

• Stock solutions are concentrated solutions of active (drug) or inactive


(e.g. colourant or preservative) substances 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?
• 4 liters = 4000 mL
• 1:400 = 0.25% 1:2000 = 0.05%
• Use the same formula
X mL (0.25 %) = 4000 mL (0.05%)
X = 800 mL (answer)
• 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%
X (0.25%) = (3785 mL)(0.05%)
X = 757 mL (answer)
Using a Vial or Amp Stock
• We are to prepare 30 mL of a 5 mg/mL oral phenobarbital solution using 1 mL
vials with a concentration of 65 mg/mL. How much stock solution will be
required?
• Step 1: Calculate the amount of phenobarbital needed
• 30 ml x 5 mg/mL tells us we need 150 mg of phenobarbital for the solution

• Step 2: Calculate the volume of available stock needed. Our supply is 65 mg/mL,
so
65 mg = 150 mg
1 mL X
X = 2.3 mL of phenobarbital will have to be drawn up
• In order to use our formula we must calculate the percent
strength of each ingredient
• 5 mg/mL = 0.005 g/mL which is a 0.5% solution
• 65 mg/mL = 0.065 g/mL = 6.5% solution
X (6.5%) = (30 mL) (0.5%)
X = 2.3 ml of phenobarbital required (answer)
Determining Quantity of Active Ingredient in Specified
Amount of Solution Given Strength of Diluted Portion

• 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?

1000 mL = 1 g
500 mL Xg
• X = 0.5 g of silver nitrate in 500 mL of diluted solution (1:1000),
which is also the amount in 5 mL of the stronger (stock)
solution, since the 50 mL and the 5 mL are the same strength
• Example Continued

5 mL = 0.5 g
50 mL Xg
X = 5 g (answer)
Amount of Diluent Needed for
Preparing Solution of Specified Lower
Strength
• 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 = 0.133% 1:2500 = 0.04%
• Using our formula, recall that the Q2 always represents the FINAL
volume
• (300 mL) (0.133%) = X (0.04%)
• X = 997.5 or 1000 mL
Example continued
• This is the volume of our 0.04% solution; therefore, we
must subtract the volume of the 0.133% solution (the
amount we started with) from this final volume to
determine how much water or diluent was added.
1000 mL – 300 mL = 700 mL (answer)
Alligation
• Arithmetical method of solving problems
that involves mixing of solutions or solids
that have different percentage strengths
Alligation Medial
• Uses the weighted average
• Used when the percent strength of each component is
KNOWN
• Express the percent strength by a decimal fraction
• Multiply the decimal by the corresponding quantity
• Add the products and divide by the total quantity of the
mixture
• What is the percent strength of a product that is
made up of 3000 mL of 40% alcohol, 1000 mL of 60%
alcohol and 1000 mL of 70% alcohol?
• 40% = 0.4 x 3000 mL = 1200 mL
• 60% = 0.6 x 1000 mL = 600 mL
• 70% = 0.7 x 1000 mL = 700 mL
• Add total volume = 5000 mL
• Add the products 1200 mL + 600 mL + 700 mL = 2500 mL
• Divide 2500 mL by 5000 mL = 0.5 (change this to a
percent) x 100 = 50%
• Therefore by mixing these products the final product is
5000 mL of a 50% alcohol product
Alligation Alternate
• This method calculates the number of PARTS of two
or more components of a certain strength. The final
proportion allows us to use proportional parts to
make any amount of the product we wish.
• Strength of the final product must be in-between the
strengths of the components we are mixing
• Mix a 95% product with a 50% product to
get a 70% product
• Subtract 70 from 95 and get 25
• Subtract 50 from 70 and get 20
• Now we have 20 parts of 95% and 25 parts of
50%
• Remember to REDUCE 20:25 = 4:5
Example Continued
• So if we mix 4 parts of 95% and 5 parts of 50% we will get
a 70% product
• We can apply this to liquids or solids
• Say we need 1 pound of a 70% coal tar product, how
much of 95% and how much of 50% will we need?
4 = X
9 454 grams
Example Continued
• The final product is 1 pound or 454 grams that is
represented by 9 total parts (4 + 5)
• Solve for X and 201.7 grams of 95%
• 454 - 201.7 = 252.3 grams of 50%
Using Alligation Alternate When the
Quantity of One Ingredient Is Known
• How many grams of 2.5% hydrocortisone cream should be
mixed with 360 g of 0.25% cream to make a 1% hydrocortisone
cream?

2.5% 0.75 part of 2.5% cream


1%
0.25% 1.5 parts of 0.25% cream

Relative amounts: 0.75:1.5, or 1:2


Example Continued
2 parts = 360 g
1 part Xg

X = 180 g (answer)
Example
• How many grams of white petrolatum should be mixed with 250 g of
5% and 750 g of 15% sulfur ointments to prepare a 10% ointment?

12.5% 10 parts of 12.5% mixture


10%
0% 2.5 parts of white petrolatum

Relative amounts: 10:2.5, or 4:1


Example Continued
4 parts = 1000 g
1 part Xg

X = 250 g (answer)
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 the 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.
Calculations of Alcohol Dilutions
• How much water should be mixed with 5000 mL of 85% v/v alcohol to
make 50% v/v alcohol?

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