DILUTION OF LIQUIDS

OBJECTIVES
• Perform calculations for altering product strength through dilution
• Perform calculations for the preparation and use of stock solutions
• Apply allegation medical and alligation alternate in problem solving
• The strength of a pharmaceutical preparation may be increased or
decreased by changing the proportion of active ingredient to the
whole preparation.
• 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 reduction in the strength of a commercially available
pharmaceutical product may be desired to treat a particular patient,
based on the patient’s age (e.g., pediatric or elderly) or medical
status, or to assess a patient’s initial response to a new medication.
• The strengthening of a product may be desired to meet the specific
medication needs of an individual patient.
• The relationship between strength and total quantity of
pharmaceutical preparations is based on its content of active
ingredient relative to the whole.
• If the amount of active ingredient remains constant, a change in the
total quantity (volume or weight) of a preparation will alter the
strength inversely; that is, the strength decreases as the total quantity
increases, and vice versa
• Example
• 1g in 20ml = 10%w/v, 1g in 20ml = 5%
• It is seen that by increasing the volume by twice as much reduces the
strength by half.
• The following methods can be used
1. Inverse proportion
2. The equation : (1st quantity) × (1st concentration) = (2nd quantity)
× (2nd concentration), or Q1 ¥ C1 = Q2 ¥ C2
• N OT E: Many students prefer this method.
3. Traditional calculations, by determining the quantity of active
ingredient present and relating that amount to the quantity of the total
preparation
• Example calculations of dilution of liquids
• If 500 mL of a 15% v/v solution are diluted to 1500 mL, what is the
percent strength (v/v) of the dilution?
solving by proportion
1500ml = 15 (%)
500ml x (%)

= 5% v/v
• Solving by equation:
• Q1 (quantity) * C1 ( conc) = Q2 ( quantity) * C2 ( conc)
500ml * 15% = 1500ml * x%
x = 5%
• Solving by traditional calculations
• 500ml * 15% = 75ml of solute
• 75ml/1500ml * 100% = 5% v/v
• Practice question
1. 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% w/v solution
of the preservative?
• N OT E: It is often simpler to convert a given ratio strength to the
corresponding percent strength in solving certain problems. Solving by
inverse proportion:
2. Dopamine HCl injection is available in 5-mL vials each containing 40
mg of dopamine HCl per milliliter. The injection must be diluted before
administration by intravenous infusion. If a pharmacist dilutes the
injection by adding the contents of one vial to 250 mL of 5% dextrose
injection, calculate the percent concentration of dopamine HCl in the
infusion. Solving by traditional calculations:
• Strengthening of pharmaceutical product
• This may be achieved by a like product of greater active ingredient or
by the admixture with a calculated quantity of a like product of
greater concentration.
• Example
• 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 * 60 mL = 12 mg 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.
Example
• How many milliliters o a 10% w/v stock solution should be used in
preparing 1 gallon o a 0.05% w/v solution?
1 gallon = 3785ml
3785ml X 0.05g/100ml = 1.89g
Therefore ; 1.89g X 100ml/10g = 18.9 ml
• Using the equation
• Q1 (quantity ) C1 (concentration) = Q2 (quantity) C (conc) mL x mL )
3785ml × 0. 05 %= 10 %
× = 18 . 9 mL
Practice question
How many milliliters o a 1% w/v stock solution o a certif ed red dye
should be used in preparing 4000 mL o a mouthwash that is to contain
1:20,000 w/v o the certif ed red dye as a coloring agent?
• Some interesting calculations are used in pharmacy practice in which
the strength o a diluted portion o a solution is de ined, but the
strength o the concentrated stock solution used to prepare it must be
determined.
• 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 large volumes of a diluted solution from a
pharmacy.
• Example
• How much drug should be used in preparing 50 mL o a stock solution
such that 5 mL diluted to 500 mL will yield a 1:1000 w/v solution?
• 1: 1000w/v = 1g of drug in 1000ml of solution
• 500ml * 1g/1000ml = 0.5g in 500ml of the diluted 1:1000ml w/v
diluted solution
• Note the soure of the 0.5g is 5ml of the stock solution
• Therefore, if 0.5g is in 5ml how much will be in 50ml.
• Practice questions
1. 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 0.3% w/v solution for irrigation?
2. How many milliliters of a 17% w/v concentrate of benzalkonium
chloride should be used in preparing 100 mL of a stock solution
such that 5 mL diluted to 60 mL will yield a 0.13% w/v solution of
benzalkonium chloride?
• Dilution and fortification of semisolids
• I 30 g o a 1% w/w hydrocortisone ointment are mixed with 12 g o a
nonmedicated ointment base, what would be the resulting
concentration o hydrocortisone in the mixture?
30g x 1% w/w = 0.3g hydrocortisone
30g ( hydrocortisone ointment) + 12g ( ointment base) = 42g mixture
0.3g/ 42g x 100 = 0.71% w/w
• You can still use the Q1 x C1 = Q2 x C2
• 30 (g) x 1% = 42 g x x%
• X = 0.71%
• Practice question
• As a part o a clinical study, a pharmacist is asked to prepare modif
cations o standard 22 g 2% w/w mupirocin ointments by adding the
needed quantities o either mupirocin powder or a nonmedicated
ointment base. Required or the study are a 1.75% w/w mupirocin
ointment and a 2.25% w/w mupirocin ointment. For each modif ed
ointment, calculate the quantity o component to add to a standard
ointment
Alligation
• Alligation is an arithmetical method of solving problems that involves
the mixing of solutions or mixtures of solids of different percentage
strengths. Alligation Medial. T his is a method by which the “weighted
average” strength of a mixture of two or more substances of known
quantity and concentration may be calculated.
• Example
• W hat is the percentage o zinc oxide in an ointment prepared by
mixing 200 g o 10% ointment, 50 g o 20% ointment, and 100 g o 5%
ointment?
• 0.10 x 200g = 20g
• 0.20 x 50g = 10g
• 0.05 x 100g = 5g
• Total : 350g 35g
• Then, 35g / 350g = 0.10 x 100 = 10% w/w
• Where an addition of diluent or vehicle is required, treat the strength
as zero
• W hat is the percentage strength o alcohol in a mixture o 500 mL o a
solution containing 40% v/v alcohol, 400 mL o a second solution
containing 21% v/v alcohol, and a su f cient quantity o a nonalcoholic
third solution to make a total o 1000 mL?
• 0.40 x 500ml = 200ml
• 0.21 x 400ml = 84 ml
• 0 x 100ml = 0ml
• 1000ml 284ml
• Alligation Alternate
• T his is a method used to determine the quantities of ingredients of
differing strengths needed to make a mixture of a desired strength. It
involves matching pairs of ingredients, one higher in strength and one
lower in strength than the desired strength, which lies somewhere in
between. The desired strength is placed in the center of the working
diagram.
Reducing and enlarging formula
• Pharmacists may have to reduce or enlarge formulas for
pharmaceutical preparations in the course of their professional
practice or manufacturing activities
• Formulas in the United States Pharmacopeia–National Formulary
generally are based on the preparation of 1000 mL or 1000 g of
product. Formulas from other sources may be based on other
quantities
• T he important criterion is that irrespective of the quantity prepared,
the correct proportion of one ingredient to the other in a given
formula must be maintained
Methods to reduce or enlarge formulas
• The methods of ratio and proportion, dimensional analysis, and the factor method
may be used to reduce or enlarge a pharmaceutical formula. For many, the factor
method is the simplest to use.
• Example
• From the following standard formula for Calamine Compounded Topical Suspension,
USP,1 calculate the quantity of each ingredient required to prepare 240 mL of product.
Calamine 80 g
Zinc oxide 80 g
Glycerin 20 mL
Bentonite magma 250 mL
Calcium hydroxide Topical solution, qs ad 1000 mL
Solve by ratio method
• 80g/1000ml = xg/ 240ml; x = 19.2g, Calamine
• 80g/1000ml = Xg/ 240ml; X = 19.2g, Zinc Oxide
• 20ml/ 1000ml = Xml/240ml ; X = 4.8ml Glycerin
• 250ml/ 1000ml = X ml/ 240ml; X = 60ml, bentonite magma
• And calcium hydroxide topical solution to make 240ml
• Add calcium hydroxide 240ml
Solving by dimensional analysis;
• 240ml X 80g/1000ml = 19.2g calamine
• Do the same for other ingredients
Solving by the factor method
This is based on the relative quantity of the total formula to be
prepared.
For example, in the above example, 240 mL of a 1000-mL standard
formula are to be prepared.
• The factor would be;
• 240ml ( to be prepared)/1000ml (standard formula) giving 0.24
(factor)
• Then multiply the quantity of each ingredient in the formula with the
factor.
Example 2
From the following formula or artificial tears,2 calculate the quantity o
each ingredient required to prepare a dozen 30-mL containers
• Polyvinyl alcohol 1.4 g
• Povidone 0.6 g
• Chlorobutanol 0.5 g
• Sterile sodium chloride solution 0.9%, ad 100 mL
• From the following formula for an estradiol vaginal gel, calculate the
quantity of each ingredient required to prepare 1 lb of gel
Formula
• Estradiol 200g
• Polysorbate 1g
• Methylcellulose Gel, 2% 95 g
Ib = 454g
• First determine the formula weight
• 200g + 1g + 95g = 296g
• 454g/296g = 1.534 (factor)
• Then multiply each ingredient quantity by the factor
Formulas that specify proportional parts
• Sometimes though rare, a pharmacist may come across an old
formula that indicates the ingredients in “parts” rather than in
measures of weight or volume.
• The parts indicate the relative proportion of each of the ingredients in
the formula.
• A formula for solid or semisolid ingredients may be considered in
terms of grams,
• whereas a formula of liquids may be considered in terms of milliliters
• Example
• From the following formula, calculate the quantity of each ingredient
required to make 1000 g of the ointment.
Coal tar 5 parts
Zinc oxide 10 parts
Hydrophilic ointment 50 parts
Total number of parts ( by weight) = 65
1000g will contain 65 parts
Then
We say 65 parts = 1000 g
Then 5 parts = X g
Cross multiply = 76.92 g of coal tar
The same principle should be applied to the remaining ingredients. The
final quantities will be
153.85 g of Zinc Oxide and 769.23 g Hydrophilic Ointment
Giving a total of 1000g