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
•