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Pharmaceutical calculation

AIM : To understand the basic calculations


required in Pharmaceutical practice
OBJECTIVES
• Appreciate
a)Pharmaceutical formula
b)Scaling up or down of a formula
c) Interpretation and calculation of
concentrations
d) Expression of concentration in pharmacy
e) Dilution and concentration
f) Alcohol dilutions
Pharmaceutical calculation
OUTCOME : At the end of this section
students should be able to
• a) interpret or write a pharmaceutical
formula
• b) scale up or down of a pharmaceutical
formula in order to obtain the required
ingredients for the formulation
.c) interpret or calculate percentage
concentration concentrations.
OUTCOME
• d) dilute adult preparation to children
preparation or
• e) mixing of two similar preparations of
different strengths and also dilute alcohol to
the required concentration
Introduction

• The adoption of the metric system


• Pharmaceutical calculations involve simple
arithmetic, however errors easily slips in,
therefore, rules that help to prevent errors
are strictly adopted.
• In general dispensing, a further check of the
calculation by a second person is always
recommended.
Introduction cont.
• When the ingredients in a formula adds up to
a convenient figure, as is often the case, the
quantities for any fraction of this can be
added and should be the same fraction of the
unreduced formula. For example, the
ingredients for one-fifth of a formula totalling
1000 g should add up to 200 g.
Formula
• This is the list and quantities (either relative
or specific) of ingredients in a medicinal
preparation.
• These ingredients and their quantities are
usually written vertically in the official books
(e.g. B.N.F., the Pharmacopoeias). Look at the
examples below:
Formula
• Example 1
Magnesium trisilicate powder 50 g
Light magnesium carbonate 50 g
Sodium bicarbonate 50 g
Peppermint emulsion 25 ml
Double strength chloroform water 500 ml
Purified Water to 1000 ml
Formula
• Example 2
Coal tar 6g
Zinc oxide, finely sifted 6g
Starch 38 g
Emulsifying wax 5g
Yellow soft paraffin 45 g
Formula
• Add up when only weights are involved
• Standards – BP, BNF USP etc
Scale factor (S.F.) and Formula writing
• Medicines are prepared according to
amounts required, hence, formulae are
either scale up or down.
• The amount required divided by the amount
stated in the formula is termed the scale
factor.
Scale factor (S.F.) and Formula writing
• Example, prepare 25 g of Zinc and coal tar paste
B.N.F.
Official Amounts
amounts required
( x 0.25)
Coal tar 6g 1.50 g
Zinc oxide, finely sifted 6 g 1.50 g
Starch 38 g 9.50 g
Emulsifying wax 5g 1.25 g
Yellow soft paraffin 45 g 11.25 g
100 g 25.0 g
Scale factor (S.F.) and Formula writing
• Solution:
• Calculate the scale factor first
• Multiply every ingredient by the S.F.
• S.F. = Amount required = 25 g
Final amount in formula 100 g
= 0.25
Scale factor (S.F.) and Formula writing
• Note:
• The quantities have been arranged in orderly
vertical columns. Errors caused by misplacing
the decimal point are minimised by this
procedure.

• The sum of the ‘Amounts required’ column is


the correct fraction of the sum of the ‘Official
amounts’ column
Relative quantities
• Formulas sometimes indicate relative
quantities of ingredients, or proportional
parts, to be used in obtaining any desired
total amounts.
• Example 4
Salicylic acid 1 part
Precipitated sulphur 8 parts
Hydrophilic ointment 91 parts
Number of parts of an ingredient (as specified)
Total number of parts in the formula (as specified)
x Total quantity of formula (as desired)

• From the above formula, calculate the quantity of


salicylic acid to use in preparing 30 g of ointment.

Solution:
1 (salicylic acid as specified x 30 g (formula desired)
100 (total parts specified)

= 0.3 g.
Summary
• Rules in pharmaceutical calculations are
1) further check of the calculation by a second
person is always recommended,
2) quantities should be arranged in orderly vertical
columns with the same number of figure(s) after
the decimal points,
3) adhere strictly to the method of calculating the
scale factor.
4) check if ‘to’ is in the formula,
5) check if the sum of the ‘Amounts required’
column is the correct fraction of the sum of the
‘Official amounts’ column.
Percentage Concentration Expressions

• Percentage weight in volume (% w/v) - the


number of grams of solute per 100 ml of
solution.

• It is given by the formula – concentration %


w/v = weight of solute in gram x 100
volume of solution in ml
Percentage Concentration Expressions
conti.
• Percentage volume in volume (% v/v) - Volume
in mls (cm3) of solute in 100 ml of solution. This
is usually used for liquid dissolved in another.

• Formula is
% v/v = volume of liquid in ml x 100
volume of solution in ml
Percentage Concentration Expressions
conti.
• 3. Percentage weight in weight - % w/w -
Number of grams of solute per 100 g of
solution.
Use in gas in liquid solutions of gases
• Solutions expressed in % w/w are not
affected by temp. and offers precise
description of concentration.
Percentage Concentration Expressions
conti.
• 4. Percentage volume in weight - % v/w -
Volume in mls (cm3) of solute (usually liquid)
in 100 g of solution product).
• Example
Calculate the quantity of sodium chloride
required for 500ml of a 0.9 per cent solution.

0.9%w/v solution means 0.9g of sodium


chloride in 100ml solution
500ml solution = (500/100) x 0.9g = 4.5g
Percentage Concentration Expressions
conti.
• Note:
The 4.5 g would not be added to 500 ml of
solvent because this would result in a volume
greater than the 500 ml due to the
displacement caused by solution of the
medicament. The correct procedure is to
dissolve the solid in part of the solvent and
then adjust the volume to 500 ml.
Other concentration expressions
Parts
• The Pharmacopoeias also express some
concentrations in terms of the number of
‘parts’ of solute dissolved in a stated number
of ‘parts’ of solution. Use of this method to
describe the strength of a solution of a solid
in a liquid infers that a given number of parts
by volume (ml) of solution contain a certain
number of parts by weight (g) of solid
Other concentration expressions
Parts
• An expression such as “1 in 10” means that 1
part by volume of a liquid is to be diluted
with or 1 part by weight of a solid to be
dissolved in sufficient of the diluent or
solvent to make the volume of the finished
solution 10 parts by volume.
• To avoid unnecessary bulk of solutions
• Concentration expressed in parts can be
converted to percentage concentrations
Other concentration expressions
Parts
• Example 5
Convert i) 1 in 400 to % concentrations
1 in 400 = 100 x 1 per cent = 0.25 %
`400
• 2. Molarity M,c - Number of moles of solute
in 1 liter of solution (mol l-1)
• 3. Molality m – Moles of solute in 1 kg (1000
g) of solvent. This offers a more precise
description of concentration
Other concentration expressions
Normality N
• Number of gram equivalent weight of solute in I
litre of solution.
• Gram equivalent weight is the weight in grams of
an atom or radical divided by the valence of the
atom or radical. E.g. the gram equivalent weight
of potassium is 39 g/1 = 39
Example 6
Convert 5 % w/v sulphuric acid soln to normality;
Molecular wt. of sulphuric acid is 98 g.
Other concentration expressions
Normality N
• H2SO4 has two displaceable hydrogen atoms or
valence of 2.
Hence the gram equivalent weight = 98 g/2 = 49 g
Concentration of solution = 5 g in 100 ml solution
Therefore number of gram eq. in the solution
= 5 g/49 g = 0.102

Normality N = 0.102 x 1000 ml = 1.02


100 ml
Other concentration expressions
Mole fraction X or N
Ratio of the moles of one constituent e.g. the
solute of a solution to the total moles of all
constituent (solute and solvent) i.e. mole fraction
of solute
X 1 = n1 and solvent X2 = n2
n1+n2 n1+n2

Where n1 and n2 are the numbers of moles of


solute and solvent respectively. The sum of mole
fractions of any solution is always 1.
Other concentration expressions
Mole and milligram %

• Mole percent – Mole fraction x 100.

• Milligram % - Number of milligrams of solute


in 100 mls of solution.
Other concentration expressions
Milliequivalents
• The concentrations of solutes in body fluids and
in solutions used as replacements for these fluids
are usually expressed in terms of the number of
millimoles (1 millimole – one thousandth of a
mole) in a litre of solution.

• In electrolyte replacement therapy, solutions


containing various electrolytes are injected into
the body to correct serious electrolyte
imbalances
Other concentration expressions
Milliequivalents
• The concentrations are usually expressed as
equivalents per liter or milliequivalents per
liter. A milliequivalent (mEq) of an ion is
1/1000th of the gram equivalent of the ion
and is therefore the same figure expressed in
milligrams.
• 1 mEq = ionic wt in mg
Valence
Other concentration expressions
Milliequivalents
• Milliequivalent best expresses the electrical
activity of ions in replacement fluids, which in
this instance is important.
• The gram equivalent wt. of potassium (K) is 39 g.
The mEq of K is gram equivalent wt divided by
1000. Thus, 39 g/1000 = 0.039 g = 39 mg, One
mEq of K+ (ion) combines with 1 mEq Cl- to give 1
mEq of KCl. The mEq of KCl is 74.5 mg, (1 mEq K
+
is 39 mg + mEq Cl- is 35.5 mg)
Other concentration expressions
Milliequivalents
• Water of hydration contributes to the
molecular weight of a compound but not to
the valence, and the total weight is used to
calculate mEq.
Example 8
How many mEq of Mg are there in 10 ml of 50
% solution of Magnesium sulphate injection?
The mol.wt of MgSO4.7H2O is 246.

50 % soln means 5 g MgSO4.7H2O in 10 ml.


Other concentration expressions
Milliequivalents
• Eq wt = gram mol. Wt = 246 = 123 g
Valence 2
mEq wt = 123 g = 0.123 g
1000
• Total mEq = 5 = 40.7 mEq in 10 ml.
123 mg/mEq
Dilution and Concentration
• Stock solutions
• Addition of inert substances
Example
How much of diluent must be added to 50 g of
a 10% ointment to make it a 5 % ointment ?
Mixing Different Strengths -
Proportion Calculation and Alligation

• The sum of the products obtained by


multiplying a series of quantities by their
respective concentrations equals the product
obtained by multiplying a concentration by
the sum of the quantities.
• This rule is applied in mixing of two similar
preparations, but of different strengths, to
produce a preparation of intermediate
strength.
Proportion Calculation and Alligation
Example
• 100 g of a powder containing 8 % of sulphur are to
be made from powder containing 10 % of sulphur
and powder containing 2 % of sulphur.

• Let n be the number of g of the 10 % powder req’d

• Then 100 – n g will be the wt of 2 % powder req’d

• Therefore, 10 x n + 2 x (100 – n) = 8 x 100


100 100 100
Proportion Calculation and Alligation

• 10n + 200 – 2n = 800


8n = 600
n = 75

• That is 75 g of the 10 % powder will be


mixed with 25 g of the 2 % powder.
Alligation method
• This type of calculation can also be done by an
alternate, alligation
10 2
8
6 2
• Subtract 8 from 10 = 2 (10 – 8 = 2) (required
percentage from stronger percentage)
• Subtract 2 from 8 = 6 (8 – 2 = 6) (weaker
percentage from required percentage)
Alligation method
• Then 6 parts of the 10 % powder plus 2 parts of
the 2 % powder will produce 8 parts of 8 %
powder. 100 g are required;
• Therefore, quantity of 10 % powder required
100 x 6 = 75 g
8
and quantity of 2% powder required
100 x 2 = 25 g OR 100 g – 75 g = 25 g
8
Alligation method
• Although this method produces correct
answer, it is not recommended except as a
method of checking since its logic is not
immediately obvious, and if a slip in writing a
figure is made it may not readily be apparent.
Parts Per Million (ppm).

 Occasionally used in compounding


prescription orders of very dilute
preparations.
A 0.1 % solution may be expressed as 0.1
part/100 or 1 part/1000. A 1 ppm solution
contains 1 part of solute/1 million parts of
solution; 5 ppm is 5 parts of solute/1 million
parts of solution.
Parts Per Million (ppm).

• Example
Rx
Sodium fluoride, q.s.
Purified water, q.s. 60 ml
Make solution such that when 5 ml is diluted
to 240 ml of water a 2 ppm soln results.

• The amount of NaF needed is not known


Parts Per Million (ppm).

• The concentration of NaF in the 240 ml is 2


ppm
• The NaF solution diluted into 240 ml was 5 ml

Now to calculate;
240 ml contains 2 ppm NaF
= 2 g x240 ml = 0. 00048
1,000,000
Parts Per Million (ppm).

• This concn was in the 5 ml dose diluted to the


240 ml.
• Therefore , amount of NaF needed for the 60 ml
prepn

= 0.00048 g x 60 ml = 0.00576 g = 5.76 mg


5 ml

.
Parts Per Million (ppm).
• If the prescriber had requested the
concentration in terms of fluoride ion (F-),
then the atomic weight of F- and molecular
weight of NaF are used in the calculation
Atomic weight of F- is 19, and mwt of NaF is 42
Therefore, 5.76 mg NaF = 5.76 mg x 19 g
42 g
= 2.606 mg.
Alcohol Dilutions

• The Official dilute alcohols are made from 95 %


alcohol - 95 parts by volume of ethyl alcohol (C2H
5OH) and 5 parts by volume of water and is a
volume in volume percentage solution.
• On mixing alcohol with water, contraction of
volume and rise in temperature occur and,
consequently, it is necessary to cool the mixture
to about 20oC before diluting to the final volume.
Alcohol Dilutions

• The turbidity that occurs at first is caused by


minute air bubbles evolved from the alcohol on
dilution as air is less soluble in both solvent.
• The method of calculating alcohol dilutions is as
follows;
Example
• Prepare 600 ml of 60 % alcohol from 95 %
alcohol.
• Let n = number of ml of 95 % alcohol required
Alcohol Dilutions

• These n ml will contain the same amount of


alcohol as 600 ml of 60 % alcohol
95 x n = 60 x 600
100 100

Therefore, n = 60 x 600 = 379 ml


95
• It follows that to calculate the amount of a
stronger alcohol required to make a weaker
alcohol the procedure is
Alcohol Dilutions
• It follows that to calculate the amount of a
stronger alcohol required to make a weaker
alcohol the procedure is
• Multiply the number of ml of diluted alcohol
required by the percentage strength required
and divide by the percentage of alcohol used.
• Vol. req’d x % req’d = Volume of stronger
% used alcohol to be used
Proof Spirit

• In U.S. the strength of pure alcohol or


absolute alcohol (C2H5OH) is calculated by
means proof degrees.
• 100 proof spirit contains 50 % (by volume) or
42.5 % (by weight) of C2H5OH, and its specific
gravity is 0.93426 at 15.56oC. Thus, 2 proof
degrees equals 1 % (by volume) of C2H5OH.
100 ml proof spirit contains 50 ml of C2H5OH
and water added to 100 ml.
Proof Spirit

Use of impure powders for
preparations


Formulation of liquid preparations
from tablets
• Liquid preparation are the right dosage form
for the infant, children and the very elderly
who cannot swallow tablets.
• When a pure powders are unavailable to
serve a prescription order, the pharmacists
requires to prepare this from tablets.
Formulation of liquid preparations
from tablets

Formulation of liquid preparations
from tablets

Formulation of liquid preparations
from tablets

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