Pharmaceutical Calculations

By:- Demis. D 1
2
 1. Pharmaceutical Calculations
 area of study that applies basic principles of mathematics to the preparation,
safe and effective use of pharmaceuticals
 the scope of PC includes computations related to:
 drug substances and pharmaceutical ingredients

 biological activity and pharmacokinetics of drugs

 statistical data from basic research and clinical drug studies

 pharmaceutical product development and formulation

 prescriptions and medication orders

 Pharmacoeconomics 3
• In community pharmacies, pharmacists receive, fill, and dispense
prescriptions and provide relevant drug information to ensure their
safe and effective use.
• Prescriptions may call for prefabricated pharmaceutical products
manufactured in industry or
• They may call for individual components to be weighed or measured
by the pharmacist and compounded into a finished product.

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 Some Fundamentals of Measurements
 To have a complete understanding of various types of calculations it is
desirable that the pharmacist should have a thorough knowledge regarding
weights & measures which are used in calculations.
 The knowledge & application of pharmaceutical calculations are essential for
the practice of pharmacy & related health professionals.
 There are three systems of weights and measures
 The Imperial systems
 The Metric systems
 Household systems
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 A. Imperial Systems
 Imperial system is an old system of weight & measures

 Avoirdupois System
 widely used systems in the US in measuring body weight and in selling goods by
the ounce or pound
 pound is the standard unit for weighing & all measures of mass are derived from
the Imperial standard pound (lb)
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 Avoirdupois System Cont

 1 ounce (oz) = 437.5 grain(gr)

 1 pound (lb) = 7000 grain
 1 pound = 16 oz
 1 dram = 60 grain
 1 quart = 40 flounces (fluid ounces)
 1 pint (o) = 20 fluid ounces
 1 flounce = 480 minims
 1 fl dram = 60 minims

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 Apothecaries Systems
 Also known as the Troy system widely used in the UK

 Grain is the standard unit in this system & all other weights are derived from it
 ounce (oz) = 480 grain
 lb = 12 ounces (oz)
 lb = 5760 gr
 Example, If the weight of a powder is lb, what is the weight of this powder in the
standard unit of apothecaries system?

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 Measurement of capacity (volume) in
Imperial system

 The standard units for capacity is same for both Avoirdupois & Apothecaries
Systems
 Gallon is the standard unit & other measures of capacity are derived from it
 1 gallon = 160 fluid ounces = 4 quart = 8 pint (O)
 1 gallon = 76800 minims
 1 gallon, US = 3785 mL
 1 gallon, UK = 4545 mL

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 B. International System of Units
 Metric system was developed in the late 18th century in France
 It is the accepted system of measure for scientists all around the world because of
its simplicity
 The two most common units in pharmacy are grams (weight) and liters (volume)
 A liter is the standard unit for measurement of capacity & all measures of capacity
are derived from it
 A kilogram is the standard unit for measurement of weight & all other measures
are derived from it
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 C. Household Systems

 Though inaccurate, the use of the household system of measurements is on the rise
because of an increased home health care delivery

 In this system, the patients use household measuring devices such as teaspoons,
dessertspoon, tablepoons, wine-glass, coffee cups, glasses etc.

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 Conversion Tables
 The pharmacopeia uses only metric system in formulae, but the prescription still
written in the imperial system by many physicians, so a conversion table is used
by pharmacists
Metric system Imperial system
1 kilogram (kg) 2.2 lb (pound)
30 g 1 ounce
454 g 1 pound (avoir)
1g 15.4 grain
65 mg 1 grain
1000 ml 1 quart
500 ml 1 pint
30 ml 1 fluid ounce
5 ml 1 fluid dram
1 ml 15 minims

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 Conversion table for Domestic Measures
Domestic measure Metric measure Imperial measure
1 drop 0.06 ml 1 minim
1 teaspoonful 5 ml 1 fluid dram
1 dessertspoonful 10 ml 2 fluid dram
1 tablespoonful 15 ml 3 fluid dram
1 wine-glassful 30 ml 1 fluidounce
1 coffee cup 180 ml 6 fluidounce
1 tumblerful/glass 240 ml 8 fluidounce

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 Arabic Numerals/ Decimal system

 These system uses numerals 1, 2, 3, 4, 5, 6, 7, 8, 9, & 0

 Arrangement of the numerals determines the value of the number.
 For example, digits 4, 7, and 2 placed together (472) represent the number four
hundred seventy-two
 A decimal point (.) separates whole numbers, or units, from fractional numbers, or
fractional units.
 All numbers on the left side of the decimal point are whole numbers, while those
placed on the right of the decimal point are considered fractional units.

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 Roman Numerals
 The Roman numeral system does not utilize numerals, the putting together of
alpha characters that follow specific rules represents each number.
 The alpha characters used are c, d, i, l, m, v, and x
 These letters can be small cases or capitalized—it does not matter, each letter
represents a specific number.
 I or i = 1 V or v = 5
 X or x = 10 L or l = 50
 C or c = 100 D or d = 500 M or m = 1000

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 Roman Numerals
 The Roman numeral system is not used to do calculations, but used to document
values or quantities only.
 In order to perform calculations, Roman numerals have to be converted to Arabic
numerals.

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 Rules for Conversion to Arabic numerals

 When a Roman numeral is repeated, it doubles its value; when repeated three
times, it triples its value.
 Example: I = 1, II = 2, III = 3, X = 10, XX = 20, XXX = 30
 When Roman numeral (s) of lesser value follows one of greater value, they are
added.
 E.g., VI = 5 + 1 = 6, XVI = 10 + 5 +1= 16

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 Rules for Conversion to Arabic numerals
 When Roman numeral (s) of lesser value precedes one of a greater value, they
are subtracted from the greater value numeral: e.g. IX = 10 – 1 = 9; XL = 50 – 10
= 40

 When the Roman numeral of a lesser value is placed between two greater values,
it is first subtracted from the greater placed after it, & then that value is added to
the other numeral (s) (i.e., subtraction rule applies first, then the addition rule)
 e.g. XXIX = 10 + 10 + (10 – 1) = 29; XIV = 10 + (5 – 1) = 14

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 Rules for Conversion to Arabic numerals

 When possible, largest value numerals should be used.

 e.g. 15 is written as XV but not as VVV
 Roman numeral (s) may not be repeated more than three times in succession:
e.g. 4 is written as IV but not as IIII

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 Fundamentals of Measurement & Calculations

 Weighing and measuring are two of the most important aspects of dispensing,
compounding, and administration of medications.
 Successful performance of dispensing & compounding operations in a
pharmacy depends on a thorough understanding of the principles of the
measuring instrument and strict adherence to the procedures of its care and
use.

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 Balance Sensitivity

 sensitivity of an instrument is its ability to detect small changes in the

quantity that are being measured

 a sensitive instrument can quickly detect a small change in measurement.
 measuring instruments that have smaller-scale parts are more sensitive.
 sensitive instruments need not necessarily be accurate.
 Sensitivity requirement is the minimum weight required to move the pointer
by one division on the scale.

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 Balance Sensitivity Cont…

 Minimally, a Class A prescription balance should be used in all prescription

compounding procedures.
 Most commercially available Class A balances have:-
 sensitivity requirement (SR) of 6 milligrams or less with no load and with
a load of 10 grams in each pan
 a maximum capacity of 120 grams
 minimum amounts that can be weighed with an error of not more than 5%
is 120 mg

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 Percent Error
 Difference between an individual measurement & true value (accepted reference
value) of the quantity being measured
 Sensitivity requirement (SR) is related to the percent error or maximum potential
error by the equation,
 %Error = SR × 100/quantity to be weighed (Q)
 Percent error (%E) can also be figured by the formula :
 %E = (Actual value − Intended value) x 100
(Intended value)

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 Example Solved Problems

 Example 1 : In an attempt to weigh 200 mg on prescription balance, a pharmacist

realized that it had 8% error. What is the sensitivity requirement of that balance?
SR = Error % x Q = 8/100 x 200 mg = 16 mg
 Example 2: What is the smallest quantity that can be weighed with a potential
error of not more than 5% on a balance with a sensitivity requirement of 4 mg?
Q = SR /Error % = 4 mg /0.05 = 80 mg

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 Accuracy
 Closeness of agreement between a measured quantity value and a true quantity
value of a measured.

 Precision
 Closeness of agreement between indications or measured values obtained by
replicate measurements on the same or similar objects under specified conditions.

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 Significant Figures
 A significant figure is a digit that represents an actual measurement
 Rules for Determining Significant Figures
 All digits that are not zeros are significant

 325 ml has three significant figures

 1.325 g has four significant figures

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 Significant Figures
 The significance of a zero depends on where it is compared to the nonzero digits and the
decimal points.
i. Zeros appearing between nonzero digits are significant
 40.7 L has three significant figures
 32006 m has five significant figures

ii. Zeros appearing in front of nonzero digits are not significant (place holder zeros/leading
zeros are not significant)
They are included merely to show the location of the decimal point and thus give place value
to the digits that follow.
 0.0 572 m2 of foil has three significant figures
 0.0002 g of RNA has one significant figure 27
 Significant Figures
iii. A final zero or trailing zeros are significant ONLY if there is a decimal place in
the number: e.g.
 0.00500 = has three significant figures
 2000 = has only one significant figure
iv. If the zeros come after non-zero integers and come after the decimal point, they are
significant: e.g.
 9.89000 has six significant figures
 201.00 has five significant figures

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 Examples

Assuming that the following numbers are all denominate:

• In 12.5, there are three significant figures; in 1.256, four

significant figures; and in 102.56, five significant figures.
• In 0.5, there is one significant figure. The digit 5 tells us how many
tenths we have. The nonsignificant 0 simply calls attention to the
decimal point.
• In 0.05, there is still only one significant figure, as there is in 0.005.
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 Examples…

• In 0.65, there are two significant figures, and likewise two in 0.065
and 0.0065.

• In 0.0605, there are three significant figures. The first 0 calls

attention to the decimal point, the second 0 shows the number of
places to the right of the decimal point occupied by the remaining
figures, and

• the third 0 significantly contributes to the value o the number. 30

 Pharmaceutical Measurements

 It is an important part of pharmacy practice that focuses on the equipment &

methods used in the accurate measurement of therapeutic & pharmaceutical
materials in the community & institutional practice of pharmacy
 It is employed in community & institutional pharmacies, in pharmaceutical
research, in the development and manufacture of pharmaceuticals, in chemical
and product analysis, and in quality control

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 Measurement of volume
 Common instruments for the pharmaceutical measurement of volume range from
micropipets & burettes used in analytic procedures to large, industrial-size
calibrated vessels.
 Selection of measuring instrument should be based on the level of precision
required.
 Most common instruments for measuring volume are cylindric & conical (cone-
shaped) graduates.
 For measurement of small volumes, however, the pharmacist often uses a
calibrated syringe or, when required, a pipette.
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 Measurement of volume
 Cylindric graduates are calibrated in metric units, conical graduates are usually
dual-scale- calibrated in both metric & apothecary units of volume
 As a general rule, it is best to select the graduate with a capacity equal to or just
exceeding the volume to be measured
 Measurement of small volumes in large graduates tends to increase the size of the
error

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 Measurement of volume
 The design of a volumetric apparatus is an important factor in accuracy
measurement; the narrower the bore or chamber, the lesser the error in reading the
meniscus & the more accurate the measurement
 According to USP, a deviation of 1 mm in meniscus reading causes an error of
approximately 0.5 mL when a 100 milliliter cylindric graduate is used & an error
of 1.8 mL at the 100 milliliter mark in a comparable conical graduate

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 Measure of Weight
 Primary unit of weight in SI is the gram, which is the weight of 1 cm3 of
water at 4oC , its temperature of greatest density
 All pharmaceuticals are weighed at least on a Class A prescription balance
to meet standard requirements
 Solid and semi-solid substances are weighed on special weighting papers
which are different from powder papers
 paper protects pans of prescription balance from chemical reactions &
eliminates the need for repeated cleaning

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 Aliquot Method of Weighing & Measuring

 When a degree of precision in measurement is beyond the capacity of the

instrument at hand is required, the desired precision is achieved by calculating
and measuring in terms of aliquot parts
 An aliquot is a fraction, portion, or part that is contained an exact number of
times in another
 For example, five is the second aliquot of ten, two is the fifth aliquot of ten, four
is the fifth aliquot of twenty

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 Aliquot Method of Weighing
 A method by which small quantities of a substance may be obtained within the
desired degree of accuracy by weighing a larger-than-needed portion of the
substance, diluting it with an inert material, then weighing a portion (aliquot) of the
mixture calculated to contain the desired amount of the needed substance.
 This method is used when the desired quantity of ingredients is below the lower
limits of Class A prescription balance

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 Steps to Measure by Aliquot Method
 Calculate the smallest quantity of a substance that can be weighed on the
balance with the desired precision

 Select a multiple of the desired quantity that can be weighed with the required
precision ( amount equal to or greater than the minimum weighable amount)
 Dilute the multiple quantity with an inert substance
 Weigh aliquot portion of dilution that hold desired quantity
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 Example Solved Problems
1. A torsion prescription balance has a SR of 6.5 mg. Explain how you would weigh
15 mg of atropine sulfate with an accuracy of 5%, using lactose as the diluent
 Weigh 10 x 15 mg or 150 mg of atropine sulfate
 Dilute with 1150 mg of lactose
to make 1300 mg of dilution
 Weigh 1⁄10 of dilution, or 130 mg, which will contain 15 mg of atropine
sulfate

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 Problems to be Solved

1. A prescription calls for 50 mg of chlorpheniramine maleate.

Using a prescription balance with a sensitivity requirement of 6 mg,
explain how you would obtain the required amount of
chlorpheniramine maleate with an error not greater than 5%.
2. A prescription balance has a sensitivity requirement of 0.006 g.
Explain how you would weigh 0.012 g of a drug with an error not
greater than 5%, using lactose as the diluent.
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 Measuring Volume by the Aliquot Method
 The aliquot method of measuring volume, which is identical in principle to
the aliquot method of weighing, may be used when relatively small
volumes must be measured with great precision:
1. Select a multiple of the desired quantity that can be measured with the required
precision
2. Dilute multiple quantity with a compatible diluent ( solvent for the liquid to be
measured) to an amount evenly divisible by the multiple selected
3. Measure the aliquot of the dilution that contains the quantity desired

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 Example Solved Problems
1. A formula calls for 1 mL of HCl. Using a 10-milliliter graduate calibrated from 2
to 10 milliliters in 1-milliliter divisions, explain how you would obtain the
desired quantity of HCl by aliquot method
1. Measure 2 x 1 mL, or 2 mL of the acid
2. Dilute with 2 mL of water
to make 4 mL of dilution
3. Measure 1⁄2 of dilution, or 2 mL of dilution which will contain 1mL of hydrochloric acid.

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• A prescription calls for 0.2 mL of clove oil. Using a 5-mL graduate calibrated
in units of 0.5 mL, how would you obtain the required amount of clove oil
using the aliquot method and alcohol as the diluent?
• If 5 is chosen as the multiple, then:

• 1. Measure 5 × 0.2 mL 1 mL of clove oil

• 2. Dilute with 4 mL of alcohol

to make 5 mL of dilution
• 3. Measure 1/5 of the dilution, or 1 mL, which contains 0.2 mL of clove oil
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 Density, specific gravity, specific volume
 Density (d) is mass per unit volume of a substance expressed as grams per
cubic centimeter (g/cc); D = m/v.
 Specific gravity (sp gr) is a ratio of weight of a substance to the weight of an
equal volume of a substance chosen as a standard, both substances at the
same temperature.
 Water is used as standard for the specific gravities of liquids & solids; the
most useful standard for gases is hydrogen.

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 Density, specific gravity, specific volume
 In the metric system both density & specific gravity are numerically equal.
 Substances with specific gravity less than 1 are lighter than water ; whereas
substances with specific gravity greater than 1 are heavier than water.
 The density of a substance is a concrete number (1.8 g/mL), whereas specific

gravity is an abstract number (1.8).

 Density varies with the units of measure used, specific gravity has no dimension-
constant value for each substance.

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 Pharmaceutical /Clinical Applications of sp.gr

 Specific gravity is employed when a pharmacist wishes.

 To convert the weight of an ingredient or preparation to volume or vice versa.
 To determine the weights of components in total parenteral nutrition (TPN)
admixtures.
 Specific gravity is an indicator of both the concentration of particles in the urine
and a patient’s degree of hydration.

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 Method of Calculating Specific Gravity
1. From Known Weight & Volume
 Example 1: If a liter of a cough syrup weighs 1285 g, what is its specific gravity?
Solution;
Specific gravity = Weight of substance
Weight of equal volume of water
Specific gravity = 1285 g/1000 g = 1.285

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 2. From Pycnometer or Specific Gravity Bottle

 A pycnometer is a special glass bottle used to determine specific gravity.

 It is generally available for laboratory use in volumes ranging from 1 mL to 50 mL
with affixed thermometer.
 Pycnometers have fitted glass stoppers with a capillary opening to allow trapped
air and excess fluid to escape.
 In using a pycnometer, it is first weighed empty & then weighed again when filled
to capacity with water & then when filled with liquid of interest.

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 Figure : Examples of pycnometers used to determine
the specific gravity of liquids. Shown are 1-mL and
25-mL sizes

 E.g., A pycnometer weighs 21.62 g. When filled with water, it weighs 46.71 g &
it weighs 43.28 g when filled with another liquid. Calculate the specific gravity
of the liquid.
 Specific gravity = weight of substance/ weight of equal volume of water =
43.28 g – 21.62 g/46.71 g – 21.62 g =0.86
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 3. Displacement or Plummet Method
 It is based on Archimedes’ principle
 states that a body immersed in a liquid displaces an amount of the liquid equal to its
own volume and suffers an apparent loss in weight equal to the weight of the displaced
liquid.
 Thus, we can weigh a plummet when suspended in water and when suspended in a
liquid the specific gravity of which we want to determine.
 Example 1: A glass plummet weighs 14.35 g in air, 11.40 g when immersed in water &
8.95 g when immersed in sulfuric acid. Calculate the specific gravity of the acid.
sp gr = 14.35 g – 8.95 g /14.35 g – 11.40 g = 5.4/2.95 = 1.83

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 Specific Volume
 It is an abstract number representing the ratio of the volume of a substance to the
volume of an equal weight of another substance taken as a standard, both having
same temperature.
 Sp.gr is a comparison of weights of equal volumes, whereas specific volume is a
comparison of volumes of equal weights.
 Specific gravity and specific volume are reciprocals.
 i.e. specific gravity x specific volume = 1
Specific volume = volume of substance
volume of equal weight of water

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 Example of Specific Volume Calculation

1. If 120 g of acetone measures 150 mL, what is its specific volume?

Solution
Specific volume = 150 ml/120 ml = 1.25
2. If the specific volume of sulfuric acid is 0.55, what is its specific gravity?
Solution; Specific gravity x specific volume = 1
Specific gravity = 1/specific volume = 1/0.55 = 1.82

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 2. Percentage Calculations
 Objectives
 Upon completion of this chapter, the student will be able to:
 Define the terms percentage, ratio strength and proportion
 Define the expressions percent weight-in-volume, percent volume-in -volume, and
percent weight in- weight
 Convert percent strength to ratio strength & ratio strength to percent strength
 Calculate the percentage strength and ratio strength of a pharmaceutical preparation

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 Percentage (Percent Strength)
 The term percent & its corresponding sign (%) mean ‘by the hundred’ or ‘in a
hundred,’ and percentage means ‘rate per hundred’
 Percent is the most common way to represent drug strength or concentration :
 used to express concentration of intravenous (IV) solutions & topical
medications (creams, ointments)

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 Percentage Preparations
 Percentage concentrations of active & inactive constituents in various types of
pharmaceutical preparations are defined as follows by the USP:
 Percent weight-in-volume (w/v): number of grams of a constituent in 100 mL of
solution or liquid preparation
 Percent volume-in-volume (v/v) : number of milliliters of a constituent in 100
mL of solution or liquid preparation
 Percent weight-in-weight (w/w) : number of grams of a constituent in 100 g of
solution or preparation

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 Percentage Preparations
 The term percent, or the symbol %, when used without qualification means for:
 solutions or suspensions of solids in liquids & solutions of gases in liquids,
percent weight-in-volume
 solutions of liquids in liquids, percent volume-in-volume
 mixtures of solids or semisolids, percent weight-in-weight

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 Examples of Weight-in-Volume Calculations

1. If a pharmacist dissolved the contents of eight capsules, each containing 300 mg of

clindamycin phosphate, into a sufficient amount of an astringent liquid base to
prepare 60 mL of topical solution, what would be the percentage strength (w/v) of
clindamycin phosphate in the prescription?
Solution
 Weight of clindamycin = 300 mg x 8 = 2400 mg = 2.4 gm
 % w/v = 2.4 g/60 mL x 100 % = 4 % w/v

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 Examples of Volume-in-Volume Calculations

1. What is the percentage strength (v/v) if 225 g of a liquid having a specific gravity
of 0.8 is added to enough water to make 1.5 liters of the solution?
Solution
 % v/v = 281.25 mL /1500 mL x 100% = 18.75 % v/v
2. How many liters of a mouthwash can be prepared from 100 mL of cinnamon flavor
if its concentration is to be 0.5% (v/v)?
Amt of mouthwash = 100 x 100/0.5 = 20 L

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 Examples of Weight-in-Weight Calculations
1. How many grams of sucrose must be added to 475 mL of water to make a 65% (w/w)
solution?
Solution
65 %/35% = x/475 g → x = 65 x 475 g/35 = 882.14 g
2. How many grams o a drug substance should be added to 240 mL o water to make a 4%
(w/w) solution?
3. A metronidazole vaginal gel contains 0.75% of drug in 70 g tube. An applicator will hold
5g of gel for each administration. How much drug will be contained in each application?
Amount in each applicator = 0.525 g/70 g x 5 g = 37.5 mg

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 Ratio Strength
 It is a relation or comparison of two like quantities.
 Can be expressed as quotient, fraction, percentage or decimal.
 Used to express the concentrations of weak solutions.
Can be written as a : b = a/b = a ÷ b.
 Example 1: A certain injectable contains 2 mg of a drug per milliliter of solution.
What is the ratio strength (w/v) of the solution?
Ratio strength w/v = 0.002 g/mL = 1: 500.

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 Proportion Strength
 It is statement of equality between two fractions or ratios.
 Used in dosage form calculations, specially in finding drug concentration per
teaspoonful or in the preparation of bulk or stock solution of certain medication
 The following forms are used to express proportions
 a : b = c : d, a : b :: c: d, a/b = c/d
 Example 1: How many milligrams of the drug demerol is present in 5 mL when
there are 15 mg demerol in 1 mL?
15 mg/1 mL = x /5 mL → x = 15 x 5 = 75 mg

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 Conversion of Concentration to mg/mL
 It is necessary to convert IV infusion concentrations expressed as percentage
strength, ratio strength to mg/mL
Rule for conversion
 To convert percentage strength to mg/mL multiply percentage strength, expressed
as a whole number, by 10
 Convert 4% (w/v) to mg/mL = 4 x 10 = 40 mg/mL
 To convert ratio strength to mg/mL, multiply ratio by 1000
 Convert 1:10,000 (w/v) to mg/mLx 1000 = 1 mg/10 mL

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 Conversion of Concentration to mg/mL

 To convert product strengths expressed as g/mL to mg/mL, convert the numerator

to milligrams & divide by the number of milliliters in the denominator
 Example: Convert a product concentration of 1 g per 250 mL to mg/mL
 1000 ÷250 = 4 mg/mL, answer

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 Milligrams Percent
 The term milligrams percent (mg%) expresses the number of milligrams of
substance in 100 mL of liquid.
 It is used frequently to denote the concentration of a drug or natural substance in a
biologic fluid, as in the blood.
 Quantities of substances present in biologic fluids also commonly are stated in terms
of mg/dL of fluid.
 E.g. concentration of nonprotein nitrogen in the blood is 30 mg% means that each
100 mL of blood contains 30 mg of nonprotein nitrogen.

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 Parts per Million (PPM) & Parts per Billion (PPB)

 It is number of parts of the agent per 1 million or 1 billion parts of the whole
 Used to express the strengths of very dilute solutions like maximum contaminant
levels in drinking water
 such levels are established for copper, lead, fluoride, chlorine, total organic
compounds, and other trace constituents

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 Example Calculations of PPM and PPB

1.If a city water supply has a limit of 250 ppm of nitrate ion, what is the maximum
amount of nitrate ion, in grams, that may be present in a 10,000-gallon reservoir?
Solution
Amount of nitrate ion in grams = 250 g/1000000 mL x 3785 mL/gallon x 10,000
gallon = 9462.5gram

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 Example Calculations of PPM and PPB
2. If commercially available insulin preparation contains 1ppm of proinsulin, how
many μg of proinsulin would be contained in 10-mL vial of insulin?
Solution
Amount of proinsulin = (1 grm /1,000,000 mL) x 10 mL
= 0.00001 grm = 10μg

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 3. Calculation of Doses and Formulas
 Objectives
 At the end of this chapter, the student will be able to:
 differentiate between various kinds of doses.
 perform calculations of doses involving household measures.
 perform calculations pertaining to the quantity of a dose, the
dosage regimen, and the supply of medication required for
the prescribed period.

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 Definitions of Terms

 Dose is the amount of medication that must be taken at one time to

produce the optimum therapeutic effect.

 The dose may be expressed as a single dose: the amount taken at one time; a

daily dose; or a total dose: the amount taken during the course of therapy.
 Dosage is the rate of application of a dose: no. of time the drug to be taken

( e.g. 500 mg two times per day).

 Dosage Regimen is the schedule of dosing medication ( treatment plan); e.g.

two times per day for 07 days. 69

 Dose Measurement
 A measuring devices used in dose measurement includes:
 calibrated droppers & cups for oral liquids
 syringes and intravenous sets for parenteral medication
 household devices like teaspoonful & tablespoonful

Calibrated cups Calibrated droppers Calibrated oral dispenser

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 Calibration of Droppers
 A dropper is calibrated by counting drops of a liquid as they fall into a graduate
until a measurable volume is obtained.
 The number of drops per unit volume is then established.
 Official dropper is calibrated to deliver approximately 20 drops of water per
milliliter.
E.g. If a pharmacist (druggist) counted 50 drops of a medication in filling a graduate
cylinder to the 2.5-mL mark, how many drops per milliliter did the dropper deliver?
Solution , drop/mL = 50 drops/2.5 mL = 20 drop/mL

71
 General Dose Calculations
 It is necessary to calculate the size of a dose, the number of doses, or the total
quantity of medication to dispense.
 For calculations the following equation is useful with the terms rearranged
depending on the answer required.

 units of weight or volume must be the same for the total quantity and size of
the dose.

72
 General Dose Calculations Example

1. If the dose of esomeprazole is 20 mg, how many doses are contained in 5 g?

No of doses = Total quantity/Size of dose
= 5 g x 1000 mg/g = 250
20 mg
2. How many teaspoonfuls would be prescribed in each dose of an elixir if 120
mL contained 12 doses?
Size of dose = 120 mL /12 = 10 mL = 2 tsp

73
 General Dose Calculations Example
1.A physician prescribed 125 mg of ciprofloxacin q.i.d. for 10 days for the treatment
of bacterial bronchitis
(a) How many doses are needed?
(b) How many milliliters of ciprofloxacin oral suspension containing 250 mg per 5
mL should be dispensed?
No of doses = 4 x 10 = 40
Total quantity = size of dose x No of doses = 125 mg x 40 = 5 g
mL needed = 5000 mg x 5 mL/250 mg = 100 mL

74
 Pediatric & Geriatric Dosing
 Adjustment of dose & dosing regimen for children & elderly needs special
consideration.
 Drug dosage is determined on the basis of specific patient parameters:
 Age, body weight, and body surface area are factors in determining the doses of
drugs for pediatric & elderly patients.

75
 Drug Dosage Based on Age

 The age of the patient is a consideration in the determination of drug dosage.

 Neonates have immature hepatic and renal functions that affect drug

response.

 The elderly, in addition to diminished organ function, have concomitant.

pathologies & increased sensitivities to drugs.

76
 1. Young’s Formula

 The formula is used for calculating doses for children 2 years of age.
 Example: What will be the dose for a child of 8 years if the adult dose of
a drug is 400 mg?
 Solution, Dose = (8/8+12) 400 mg = 160 mg

77
 2. Dilling’s Formula

 The formula is used for calculating doses for children in between 4 to 20

years of age.
 Example: What will be the dose for a child of 10 years is the adult dose a
drug is 600 mg?
 Dose for a child = (10/20) x 600 mg = 300 mg

78
 3. Freid’s Formula

 The formula is applicable only for infants.

Example Problem:
1. What is the dose for an 8 months old of infant if the average adult dose of
drug is 250 mg?
Dose for a child = (8/150) x 250 = 13.3 mg

79
 Drug Dosage Based on Body Weight
 The usual dose is expressed as a specific quantity of drug per unit of patient
weight : milligrams of drug per kilogram of body weight (mg/kg).
 makes the quantity of drug administered specific to the weight of the patient
being treated.
 A useful equation for the calculation of dose based on body weight is:

80
 Dosage Based on Weight, Example
1. The dose of a drug is 500 mcg/kg of bodyweight. How many mgs should be
given to a child weighing 55 lb.?
Solution
Dose mg = 55 lb x 500 mcg/2.2 lb = 12.5 mg
2. A patient weighing 120 lb. was administered 2.1 g of a drug supposed to be dosed
at 30 mg/kg. Was the dose administered correct, or was it an overdose, or was it an
under dose?
Dose = 120 x 30/2.2 = 1636.4 mg = 1.636 g, over dose

81
 Drug Dosage Based on Body Surface Area
 BSA method of calculating drug doses is widely used for two types of patient
groups: cancer patients receiving chemotherapy and pediatric patients
 BSA can be calculated using Mosteller rule

 E.g. Calculate BSA of a boy of height 165cm & weighing

65kg
BSA = 165 x 65/3600 = 1.726 m2 82
 Dosing Tables
 For certain drugs, dosing tables may be provided to determine the
approximate dose based on a patient’s body surface area.
Table: Pediatric dosing Guideline for a hypothetical dug based on BSA

83
 Dosage based on BSA Calculation
1.Using the above table find the dose of the hypothetical drug at a dose level of 400
mg/ m2 for a child determined to have a BSA of 1.25 m2 , answer: 500 mg
2.If the adult dose of a drug is 100 mg, calculate the approximate dose for a child
with a BSA of 0.86 m2
Solution,
Dose = 0.86 m2 x 100 mg/1.73 m2 = 49.71 mg = 50 mg

84
 Nomograms
 A graphic representation of numerical relations, which includes both weight and
height.
 BSA of an individual is determined by drawing a straight line connecting the
person’s height and weight.
 The point at which the line intersects the center column indicates the person’s BSA
in square meters.
 The dose is calculated based on BSA obtained from nomogram using equation:

85
Nomograms

86
 Nomograms Calculation, Example

1. If the daily dose of a drug is given in the literature as 8 mg/kg of body weight or
350 mg/m2, calculate the dose on each basis for a patient weighing 150 lb &
measuring 5 ft. 8 inch in height.
Solution
Dose = 8 mg/kg x 150lb/2.2 lb/kg = 545 mg based on weight
Dose = BSA x AD = 1.8 x 350 mg/m2 = 630 mg

87
 Drug-Specific Clinical Equations
 For certain clinical conditions, there are equations that are useful for

determining patient requirements.

 The following equation is used in determining the amount of iron required to

bring hemoglobin values to normal levels:

 Iron required (mg) =
Example
1. Calculate the number of milliliters of an iron dextran solution containing 50 mg/mL
of iron to be administered to a 150 lb patient with a hemoglobin value of 7.4 g/dL
Iron required = 45 ml, answer 88
 Reducing and Enlarging Formulas
 In pharmaceutical preparations pharmacists need to reduce or enlarge formulas
 The quantities of each ingredient required for a smaller or greater quantity is
obtained by reducing or enlarging the specified formula, while maintaining the
correct proportion of one ingredient to the other
Total quantity desired

Conversion Factor =
Total quantity of official formula

89
 Calculations of Reducing & Enlarging Formulas

1. If a formula for 1000 mL contains 6 g of a drug, how many grams of drug are needed to
prepare 60 mL of the formula?
CF = 60 mL/1000 mL = 0.06
Q desired = CF x Quantity of official formula = 0.06 x 6 = 0.36 g
2. From the following formula for 40 sertraline capsules, calculate the amount of each
ingredient necessary to prepare 250 capsule.
Rx Sertraline Hydrochloride 300 mg Required x 6.25
Silica Gel 6g ‘ ‘
Calcium Citrate 4g ‘ ‘

CF = 250/40 = 6.25

90
 Calculations in Contemporary Compounding

 Pharmaceutical Compounding is the process by which active ingredients

combined with additives in the preparation of prescriptions & medication orders
to meet the specific needs of individual patients.
 Compounding is an activity for which pharmacists are uniquely qualified by
virtue of their education, training, and experience.

91
 Constitution of Dry Powders

 Antibiotics lose their potency in a short period when prepared in a liquid dosage
form.
 To enhance the shelf-life of these drugs, they are provided in dry powder form for
reconstitution.
 After constitution, the solution or suspension is stable in the quantities usually
dispensed, for up to 10 days at room temperature or 14 days if maintained under
refrigeration (oral).

92
 Calculations for the Constitution of Dry Powders

1.AUGMENTIN powder for oral suspension is prepared prior to use by adding 84

mL of purified water to contents of container to prepare 100 mL of suspension. If a
tsp of suspension have 125 mg of amoxicillin & 31.25 mg of clavulanate potassium,
how much of each of these agents is contained in the dry powder prior to
reconstitution?
Amt of amoxicillin in 100 mL = 125 mg/5mL x100 mL = 2.5 g
Amt of clavulanate in 100 mL = 31.25mg/ml x100 mL = 0.625 g

93
 Calculations for the Constitution of Dry Powders

2. A 7.5-g bulk pharmacy vial of cefuroxime (ZINACEF) when constituted with 77

mL of sterile water for injection, contains 375 mg of cefuroxime in each 4 mL.
How many milliliters of volume were occupied by the dry powder in the vial?
Total volume = 4 mL/375 mg x 7500 mg = 80 mL
Volume occupied by dry powder = 80 mL – 77 mL = 3 mL

94
 4. Dilution and Concentration
Objectives
 At the end of this chapter, the student will be able to:
 perform calculations for altering product strength by dilution, concentration, or
fortification
 perform calculations for preparation & use of stock solutions
 apply alligation method in problem-solving

95
 Altering Product Strength in Compounding

 Strength of pharmaceutical preparation increased or decreased by changing the

proportion of active ingredients.
 A preparation made more concentrated by addition of active ingredient or
admixture with a like preparation of greater strength.
 The strength of a preparation decreased or diluted by addition of diluent or by
admixture with a like preparation of lesser strength.

96
 Relationship Between Strength & 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.
 It is generally true for all mixtures except solutions containing components that
contract when mixed together
(1st quantity) (1st concentration) = (2nd quantity) (2nd concentration)

or Q1 x C1 = Q2 x C2

97
 Calculations of Dilution & Concentration of Liquids

1.If a syrup containing 65% w/v of sucrose is evaporated to 85% of its volume, what
percentage (w/v) of sucrose will it contain?
V1 x C1 = V2 x C2
65% x V1 = 0.85V1 x C2 → C2 = 76.47%
2. How many grams of 10% w/w ammonia solution can be made from 1800 g of 28%
w/w strong ammonia solution?
Q1 x C1 = Q2 x C2 → 10% x Q1 = 28% x 1800 g
→ Q1 = 28 x 1800 g/10 = 5040 g

98
 Strengthening of a Pharmaceutical Product
 This is accomplished by the addition of active ingredient or by the admixture
with a calculated quantity of a like-product of greater concentration
1.E.g. If a pharmacist added 12 g of clotrimazol to 50 g of ointment containing 15%
clotrimazol, what would be the final strength of clotrimazol in the ointment?
Amt of clotrimazole in 50 gram ointment = 50 x .15 = 7.5 gram
Final strength = 7.5 + 12/62 x 100 = 31. 45%

99
 Stock solutions
 Are concentrated solutions of active or additives ( colorant) substances used as a
convenience to prepare solutions of lesser concentration
1.How many mL of a 1% stock solution of a certified red dye should be used in
preparing 4000 mL of a mouthwash that is to contain 1:20,000 w/v of certified red
dye as a colorant?

4000 mL x 0.005 % = V1 x 1% → V1 = 4000 x 0.005/1 = 20 mL

100
 Stock solutions Example
2. How much drug should be used in preparing 50 mL of a sol. such that 5
mL diluted to 500 mL will yield a 1:1000 solution?
Solution
1:1000 is the same as 0.1%
V1 x C1 = V2 x C2 → C1 = 500 ml x 0.1%/5 ml = 10% w/v
Because concentration of drug in 5 ml & 50 ml is the same (10%) , Q = 10%
x 50 ml = 5 g

101
 Dilution of Alcohol
 When water & alcohol are mixed, there is contraction such that the resultant
volume is less than the sum of volumes.
 Contraction of liquids does not affect weights of the components: weight/volume
of water needed to dilute alcohol to a desired w/w strength can be calculated.
E.g. How much water should be mixed with 5000 mL of 85% v/v alcohol to make
50% v/v alcohol?
5000 x 85% = 50% x V2 → V2 = 5000 x 85/50 = 8500 Ml
use 5000 mL of 85% v/v alcohol & enough water to make 8500 mL

102
 Dilution of Acids
 The strength of an official concentrated acid is expressed as percentage weight-in
weight.
 The strength of an official diluted acid is expressed as percentage weight-in-
volume.
 It is necessary, therefore, to consider the specific gravity of concentrated acids in
calculating the volume to be used in preparing a desired quantity of a diluted acid.

103
 Example Calculations of Acid Dilutions
1.How many milliliters of 37% w/w HCl acid having a specific gravity of 1.20 are
required to make 2000 mL of diluted hydrochloric acid 5% w/v?
 Amount of HCl in 2000 ml of 5% w/v = 0.05 x 2000 = 100 g
 100 g of HCl (100%) in 2000 mL of 5% w/v acid
100 % x 100 g = 37 % Q → Q = 100 x 100/37 = 270 g
Sp.gr = Wt/ Vol
mL of HCl = 270/1.20 = 225 mL

104
 Example Calculations of Solid and Semisolid Dilutions

1.How many grams of 20% benzocaine ointment and how many grams of ointment
base (diluent) should be used in preparing 2270 g of 2.5% benzocaine ointment?
Solution
2270 g x 2.5% =20% x Q → Q = 2270 *2.5/20 = 283.75 g or
284 g of 20% ointment, and 2270 g - 284 g = 1986 g of ointment base

105
 Example Calculations of Solid and Semisolid Dilutions

2. How many grams of zinc oxide should be added to 3200 g of 5% zinc oxide
ointment to prepare an ointment containing 20% of zinc oxide?
3200 g x 0.05 = 160 g of zinc oxide in 3200 g of 5% ointment
3200 g - 160 g = 3040 g of base in 3200 g of 5% ointment
In 20% ointment, diluent will represent 80% of the total weight.

20% x 3040 = 80% x X→ X = 20/80 x 3040 = 760 g of zinc oxide in the 20%
ointment, Because the 5% ointment already contains 160 g of zinc oxide, 760 g -
160 g = 600 g ZnO

106
 Triturations
 Triturations are dilutions of potent medicinal substances.
 They are 10% or 1:10 w/w mixtures.
 These dilutions offer a means of obtaining conveniently and accurately small
quantities of potent drugs for compounding purposes.
E.g. How many grams of a 1:10 trituration are required to obtain 25 mg of drug?
0.025 g x 10 = 1 g x X →X = 0.25 g

107
 Alligation
 Alligation is an arithmetical method of solving problems that involves the mixing
of solutions or mixtures of solids possessing different percentage strengths.
 There are two types of allegation methods:-
 Alligation medial
 Alligation alternate

108
 Alligation medial

 Is a method by which the ‘‘weighted average’’ percentage strength of a mixture of

two or more substances of known quantity and concentration calculated.
 Steps in calculation
 percentage strength of each component, expressed as a decimal fraction, is
multiplied by its corresponding quantity.
 sum of the products is divided by total quantity of mixture.
 the resultant decimal fraction is multiplied by 100 to give the percentage strength of
the mixture.

109
 Example, Alligation Medial

1.What is the percentage strength (v/v) of alcohol in a mixture of 3000 mL of 40%

v/v alcohol, 1000 mL of 60% v/v alcohol, and 1000 mL of 70% v/v alcohol?
Assume no contraction of volume after mixing.
Solution 0.40 x 3000 mL = 1200 mL
0.60 x 1000 mL = 600 mL
0.70 x 1000 mL = 700 mL
Totals: 5000 mL 2500 mL
2500 (mL) ÷ 5000 (mL) = 0.50 x 100 = 50% v/v

110
 Example, Alligation Medial

2. What is percentage strength of alcohol in a mixture of 500 mL of a solution

containing 40% v/v alcohol, 400 mL of a second solution containing 21% v/v
alcohol, and a sufficient quantity of a nonalcoholic third solution to make a total of
1000 mL?
Solution
0.40 x 500 mL = 200 mL
0.21 x 400 mL = 84 mL
0 .00 x 100 mL = 0 mL
Totals: 1000 mL 284 mL
284 (mL) ÷ 1000 (mL) = 0.284 x 100 =28.4% v/v 111
 Alligation alternate
 Is a method by which number of parts of two or more components of a given
strength is calculated when they are to be mixed to prepare a mixture of desired
strength.
 A final proportion permits to translate relative parts to any specific denomination
 Strength of a mixture must lie somewhere between the strengths of its components

112
Graphical presentation of Allegation Alternate

113
 Example, Alligation Alternate
1. Calculate the volume of 99.99 % alcohol required to prepare 500 mL of 80
% alcohol.
100 80
(parts of 99.99%
alcohol)

80 Relative
amounts: 80 : 20
or 4 : 1
(parts of
0 20 water)

Amount of 99.99% alcohol = 4/5 x 500 mL = 400 mL

114
 Example, Alligation Alternate

2. A hospital pharmacist wants to use three lots of ZnO ointment containing 50%,

20% & 5% of zinc oxide. In what proportion should they be mixed to prepare a

10% zinc oxide ointment?

 The two lots containing more than the desired percentage (50% and 20%) may be

separately linked to the lot containing less(5%) than the desired percentage.
50% 5 parts of 50%

20% 5 parts of 20%

10%

5% 10+ 40 = 50 parts of 5 %

Relative amount = 5:5:50 or 1:1:10

 Example, Alligation Alternate

3. How much quantity of 60%, 50%, 30% & 20% clobutasol ointment should
be mixed to get 60 gram of 40% clobutasol

116
 Example, Alligation Alternate
4. How many grams of ZnO should be added to 3200 g of 5% ZnO cream
to prepare an cream containing 20% of ZnO?
100 15
(parts of 100%
ZnO )

20 Relative
amounts: 15 : 80
or 3 : 16
(parts of 5%
5 80 cream)

Amount of ZnO needed = 3/16 x 3200 g = 600 g

117
 Example, Alligation Alternate
5. In what proportion should 20% benzocaine ointment be mixed with an
ointment base to produce a 2.5% benzocaine ointment?
20 2.5
(parts of 20%
benzocaine)

2.5 Relative
amounts: 2.5 :17.5
or 1 : 7
(parts of
0 17.5 ointment
base)

118
 Specific Gravity of Mixtures

 The methods of alligation medial and alligation alternate used in solving

problems involving specific gravities of different quantities of liquids of

known specific gravities, provided no change in volume occurs when the

liquids are mixed and that they are measured in a common denomination of

volume.

119
 Calculations, sp.gr, Alligation

1.What is the specific gravity of a mixture of 1000 mL of syrup with a specific

gravity of 1.300, 400 mL of glycerin with a specific gravity of 1.250 & 1000

mL of an elixir with a specific gravity of 0.950?

Solution
1.30 x 1000 mL = 1300 mL
1.25 x 400 mL = 500 mL
0.95 x 1000 mL = 950 mL
Totals: 24000 mL 2750 mL
sp.gr = 2750 mL ÷ 24000 mL = 1.15 120
 Example, Alligation Alternate
2. How many milliliters of each of two liquids with specific gravities of
0.950 and 0.875 should be used to prepare 1500 mL of a liquid having a
specific gravity of 0.925?
(parts of 0.950
0 .95 .05 liquid)

Relative
.925 amount:
0.05:0.025
(parts of or 2 : 1
.875 .025 0.875
liquid)

Amount of 0.950 liquid = 2/3 x 1500 mL = 1000 mL

Amount of 0.875 liquid = 1/3 1500 mL= 500 mL
121
 5. Isotonic, Buffer and Electrolyte Solutions

 At the end of this chapter the student will be able to:

 Identify between terms isosmotic, isotonic, hypertonic & hypotonic
 Apply physical chemical principles in the calculation of isotonic solutions
 State the buffer equation and apply it in calculations
 Calculate problems involving millimoles and milliosmoles
 Calculate problems involving milliequivalents

122
 Definition of Terms
 Osmosis is the diffusion of solvent through a semi-permeable membrane from low
concentration to higher concentration.
 Osmotic pressure is the pressure that applied to solution to cause passage of solvent
through a semipermeable membrane.
 In electrolyte solutions the osmotic pressure of solution vary with the concentration &
degree of dissociation of the solute.
 Tonicity is a measure of the effective osmotic pressure gradient of two solutions separated
by a semipermeable membrane.
 Unlike osmotic pressure, tonicity is affected only by impermeant solutes, as only these
exert an effective osmotic pressure.
123
Effect of osmotic pressure on solvent movement

124
 Types of Tonicity

 The tonicity of a solution is related to its

effect on the volume of a cell.
 Isotonic solution do not change volume of a
cell.
 A hypotonic solution causes a cell to swell
 hypertonic solution causes a cell to shrink

125
 Advantages of Isotonic Solutions
 Solutions intended to be mixed with body fluids are designed to have the same
osmotic pressure for greater patient comfort, efficacy & safety.

blood
no swelling
eye

nasal used with

isotonic when in
contact with no contraction
tract solutions tissues

other
body no discomfort
fluids
126
 Preparation of Isotonic Solutions
 Injections that are not isotonic should be administered slowly in small quantities to
minimize tissue irritation, pain, & cell fluid imbalance.
 Large volumes of hypertonic infusions containing dextrose, for example, can result
in hyperglycemia, osmotic diuresis, & excessive loss of electrolytes.
 Excess infusions of hypotonic fluids can result in the osmotic hemolysis of red
blood cells and surpass the upper limits of the body’s capacity to safely absorb
excessive fluids.

127
 Preparation of Isotonic Solutions
 It is generally accepted that -0.52oC is the freezing point of both blood serum and
lacrimal fluid
 When one gram molecular weight of nonelectrolyte substance with negligible
dissociation, such as boric acid, is dissolved in 1000 g of water, the freezing point
of the solution is about 1.86oC below the freezing point of pure water
 Simple isotonic solutions calculated by using this formula:

128
 Example Calculations of the i Factor
1. Zinc sulfate is a 2-ion electrolyte, dissociating 40% in a certain concentration. Calculate its dissociation (i)
factor
On the basis of 40% dissociation, 100 particles of zinc sulfate will yield:
40 zinc ions
40 sulfate ions
60 undissociated particles
or 140 particles
iZnSo4 = 40 + 40 +60 = 140/100 = 1.40

2. Zinc chloride is a 3-ion electrolyte, dissociating 80% in a certain concentration. Calculate its dissociation (i)
factor.
129
On the basis of 80% dissociation, 100 particles of zinc chloride will yield:
80 zinc ions
80 chloride ions
80 chloride ions
20 undissociated particles
or 260 particles
i = 80 + 80 +80 +20= 260/100 = 2.60

3. How much gram of sodium chloride is needed to prepare a 1000 ml solution

isotonic with blood?
g of NaCl /1000 mL = 0.52 x 58.5/1.86 x1.8 = 9.08 g/1000 mL
130
Adjustment of Isotonicity

131
 1. Freezing Point Data/Cryoscopic Method
 F.P. of blood & tears = - 0.52ºC
 Any solution with F.P. = - 0.52º is isotonic, while those solution with F.P. › - 0.52º is
hypotonic
 solute added to hypotonic sol. to reach f.p.d of blood

Where
 PSM = Percentage strength of medicament
 a = freezing point of the unadjusted solution
 b = freezing point of a 1% w/v solution of a adjusting substance
132
 Example Problem for Freezing point Method
1. How will you prepare 1% solution of boric acid, isosmotic with blood
plasma
Hint :
 f.p. of 1% w/v solution of boric acid is 0.288ºC
 f.p. of 1% w/v solution of NaCl is 0.576ºC
Solution
Percentage w/v of NaCl required = 0.52- 1x.288/.576 = 0.402%

133
 2. Sodium Chloride Equivalent Method
 NaCl equivalent “E” is amount of NaCl that is equivalent to ( has the same osmotic effect
(same f.p.d) as ) 1 gm of drug

 Procedure for calculation of isotonic sol. with E-value

1. calculate amount of NaCl alone needed to make solution isotonic
2. multiply total drug amount in g by E-value
3. subtract 2. from 1. to determine the amount of NaCl left to add
4. If other agent is to be used to make solution isotonic, divide amount of NaCl obtained in
step 3 by E-value 134
Sodium chloride equivalents (E-values) of each of the substances listed.

135
136
137
 Example, Tonicic Agent Required

1. How many grams of sodium chloride should be used in compounding the following
prescription?
R/ Ephedrine Sulfate 0.3 g
Sodium Chloride q.s.
Purified Water ad 30 mL
Make isotonic sol.
Sig. Use as directed
Step 1. 0.23 x 0.3 g = 0.069 g of NaCl represented by the Ephedrine sulfate
Step 2. 30 x 0.009 = 0.270 g of NaCl in 30 mL of isotonic NaCl solution
Step 3. 0.27 – 0.069 = 0.201 g of NaCl required to make the solution isotonic

138
 Example, Tonicic Agent Required
2. How many gram of boric acid should be used in compounding the following prescription?
R/ Phenacaine Hydrochloride 2%
Chlorobutanol 1%
Boric Acid q.s.
Purified Water ad 120 mL
Make isoton. sol.
Sig. One drop in each eye
Step 1: 0.2 x 0.02 x 120 = 0.48 g NaCl represented by phenacaine HCl
0.24 x 0.01 x 120 = 0.288 g NaCl represented by Chlorobutanol
Step 2: 120 mL x 0.009 = 1.08 g g of NaCl in 120 mL of an isotonic NaCl solution
Step 3: 1.08 – 0.768 = 0.312 g of NaCl required to make the solution isotonic
But because the prescription calls for boric acid:
Step 4: 0.312 g ÷ 0.52 ( E-value of BA) = 0.6 g of boric acid to be used

139
 Isotonic NS solution to prepare other isotonic solution

 Step 1. Calculate quantity of drug substance needed to fill the prescription order
 Step 2. Use equation to calculate volume of water needed to render a solution of
drug substance isotonic:
g of drug x drug’s E-value = mL of H2O needed to make isotonic sol. of
drug
0.009

 Step 3. Add 0.9% w/v sodium chloride solution to complete the required volume of
the prescription order

140
 Isotonic NaCl Sol. to Prepare Cont…

1.How many milliliters each of purified water & an isotonic sodium chloride solution
should be used to prepare 30 mL of a 1% w/v isotonic solution of fentanyl citrate (E
0.11)?
Step 1: Amount of fentanyl citrate = 30 x 0.01 = 0.3 gram
Step 2 : amount of H2O needed = 0.3 x 0.11/0.009 = 3.67 mL
Step 3: Amount of NS needed = 30 mL - 3.67 mL = 26.33 mL

141
 Electrolyte Solution
 Electrolyte preparations are used in the treatment of disturbances of the electrolyte
and fluid balance in the body.
 In clinical practice, they are provided in the form of oral solutions and syrups, as dry
granules intended to be dissolved in water or juice to make an oral solution, as oral
tablets and capsules and, when necessary, as intravenous infusions.
 Electrolytes in body fluids play an important role in maintaining acid-base balance,
controlling body water volumes & help to regulate body metabolism.

142
 Milliequivalent
 Is chemical activity or combining power of a substance relative to the activity of 1 mg of
hydrogen.
 Represents the amount, in milligrams, of a solute equal to 1⁄1000 of its gram equivalent
weight, taking into account the valence of the ions.
 The concentration of electrolytes in intravenous infusion fluids is most often stated in
mEq/L
 This unit of measure is related to the total number of ionic charges in solution, and it takes
note of the valence of the ions.
 In other words, it is a unit of measurement of the amount of chemical activity of an
electrolyte.
143
 Example Calculations of Milliequivalents
1.How many milliequivalents of calcium are present in a liter of a solution containing
150 mg/dL of calcium?
mEq/L = 1.5 g/L x 2 x 1000 /40 = 75 mEq/L
2. How many grams of potassium citrate should be used in preparing 500 mL of a
potassium ion elixir so as to supply 15 mEq of K+ in each 5-mL dose? Mol. wt. of
potassium citrate (C6H5K3O7·H2O) = 324 g/mol
No of mEq = 15 mEq/5 mL x 500 mL = 1500 mEq
No mEq = given mass/E. Wt → m = E. Wt x No mEq = 162 g

144
 Osmolarity
 Is the milliosmoles of solute per liter of solution
 The milliosmolar value of the whole electrolyte in solution is equal to sum of the
milliosmolar values of the separate ions
 According to the USP, the ideal osmolar concentration may be calculated according
to the equation:

 In practice, as concentration of solute↑ses , physicochemical interaction among

solute particles ↑ses, & actual osmolar values ↓se compared to ideal values
145
 Osmolarity Cont …
 Deviation from ideal condition is slight in physiologic & for more dilute solutions,
but for concentrated solution actual osmolarities is lower than ideal values.
 E.g., the ideal osmolarity of 0.9% NaCl is 308 mOsmol/L but, actually measured
osmolarity is 286 mOsmol/L.
 Osmolarity is the concentration of both permeant & impermeant substance in solution
unlike tonicity which is the concentration of impermeant, osmotically active
substances in solution.

146
 Osmolarity
 Consider two solutions: sucrose & urea both
having osmolarity of 300 mOsm/L & said to be
isosmotic ( having same osmolarity)

 When red blood cells are placed in the two solutions, those in the sucrose solution
maintain their normal volume but those placed in urea swell & eventually burst
 Differential effect of these solutions on red cell volume is related to the permeability of
the plasma membrane to sucrose and urea
147
 Example Calculations of Osmolarity
1. Calculate the ideal osmolarity of 0.9% sodium chloride injection is:
mOsmol/L = 9 g/L/58.5 g x 2 x1000 = 308 mOsmol/L
2. A solution contains 5% of anhydrous dextrose in water for injection. How many
milliosmoles per liter are represented by this concentration?
Molecular weight of anhydrous dextrose = 180
Dextrose does not dissociate, therefore the “number of species” = 1
Solutio:
5 g/100 mL x 1000 mL/L /180 g/mol x 1000 mmol/mol x 1 = 278 mOsmol/L

148
 Water & Electrolyte Balance
 Maintaining body water and electrolyte balance is an essential component of good
health.
 osmolality of body fluid is maintained within narrow limits through dietary input,
regulatory endocrine processes, balanced output via the kidneys, lungs, skin & the
GIT.
 plasma osmolality is a convenient and accurate guide to intracellular osmolality &
approximated by the formula:

 where: sodium (Na) and potassium (K) are in mEq/L, blood urea nitrogen (BUN) & glucose concentrations are in mg/100 mL
(mg/dL) 149
 Water & Electrolyte Cont….

1. Estimate plasma osmolality, in milliosmoles per kilogram, from the following data: sodium,
136 mEq/L; potassium, 5 mEq/L; blood urea nitrogen, 26 mg/100 mL; and glucose, 90
mg/dL
Solution
mOsm/kg = 2 (136 + 5) + 26/2.8 + 90/18 = 296.28 mOsm/kg

150
 Buffers and buffer solutions
 Buffer is a solution that resists changing in pH when small amount of acid or bases
is added.
 A buffered solution contains a weak acid and its salt or a weak base and its salt.
 The resistance to a change in pH is known as buffer action.
 Buffers are used to establish and maintain an ion activity within narrow limits.

151
 Pharmaceutical uses of Buffer
 For preparation of injections & ophthalmic solutions, which are placed directly into
pH-sensitive body fluids.
 To ensure maximum product stability.
 Pharmaceutical tests and assays requiring adjustment to or maintenance of a specific
pH for analytic purposes.

152
 Buffer Equation
 Let’s consider a solution containing a week acid, HA & its salt, NaAc
 NaAc is strong electrolytes which completely dissociate in solution:
NaAc (aq) Na+(aq) + Ac-(aq)
 The weak acid exists in equilibrium with its ions:
HAc(aq) + H2O (l) H3O+(aq) + Ac-(aq)
 The ionization constant for the acid is given by :
Ka = [H3O+][Ac-] / [HAc]

153
 Buffer Equation Cont…
 log Ka = log [H3O+] + log [salt] – log [acid]
pKa= -pH + log [salt] – log [acid]
 Rearranging the terms the equation becomes:
pH = pKa + log([salt]o/ [acid]o)
 This is the Henderson-Hasselbalch equation
 Buffer soln is not ordinarily prepared from weak base & their salt because of
volatility & instability of the base & due to dependence of their pH on pKw
(affected by temperature)
pH = pkw - pKb + log[Base]/[Salt]
154
 Buffer Capacity (β)
 The magnitude of the resistance of a buffer to pH changes is referred to as a buffer
capacity /efficiency/index/value
 It is the ratio of the increment of strong acid or base to the small changes in pH
brought about by addition
 β = Δ B/ ΔpH where Δ B is small increment in gram equivalent / liter of strong base
added
 The buffer capacity changes as log [salt] / [acid] changes

155
 Calculation of Buffer Capacity
 More exact equation to calculate the buffer capacity (koppel and spiro eqn):
β = 2.3 C* Ka* [H3O+]/(Ka +[H3O+])2
 Where C = total buffer concentration i.e. sum of the molar concentration of the acid
and salt
 The maximum buffer capacity occurs when pH=pKa or when [H3O+] = Ka
β max = 0.576 C where C is total buffer concentration

156
 Calculation of Buffer Capacity Cont…
Consider acetate buffer containing 0.1 M HAc & 0.1M NaAc in 1 liter of solution,
to this 0.01 M NaOH is added
HAc + NaOH NaAc + H2O
(0.1-0.01) (0.01) (0.1+0.01)
→
pH = pKa + log([salt]+[Base]/ [acid]-[Base])
 Before the addition of NaOH
pH = pKa + log([salt]/ [acid]) = 4.76
After addition of NaOH
pH= 4.76 + log (0.1+0.01/ 0.1- 0.01) = 4.85
β = Δ B/ ΔpH = 0.01/0.09 = 0.11 157
 Characteristics of Buffer Capacity
 Buffer Capacity
 is not a fixed value, but depend on the amount of base or acid added
 depends on the value of the ratio [salt]/[acid] & magnitude of the individual
concentrations of the buffer components
 greatest capacity(βmax) occurs where [salt]/[acid] = 1 and pH= pKa
 do not in general exceed a value of 0.2 because of inter-ionic effects

158
 Characteristics of Buffer Capacity
1.What is the pH of a buffer solution prepared with 0.055 M sodium acetate and 0.01
M acetic acid? The pKa value of acetic acid is 4.76 at 25oC
pH = pKa +log (salt/acid) = 4.76 + 0.74 = 5.50
2.What is the change in pH on adding 0.02 mol of NaOH to a liter of a buffer solution
containing 0.5 M of NaAC and 0.5 M acetic acid? The pKa value of acetic acid is
4.76 at 25oC
Before addition of base; pH = pKa = 4.76 , After addition of base pH = pKa +l`og
(salt+base)/(acid –bas) = 4.79
ΔpH = 4.79 – 4.76 = 0.03 unit
159
 Buffered Isotonic Solutions
 Solution that are isotonic to body fluids & resist to pH changes
 Pharmaceutical solutions that are meant for application to delicate membrane of the
body should be adjusted to same osmotic pressure as that of body fluids
 The RBC membrane permit the passage of water molecules, urea, ammonium
chloride, alcohol, boric acid

160
 Buffered Isotonic Solutions
 So the solution containing quantity of drug calculated to be isosmotic with blood is
isotonic only when blood cells are impermeable to solute & permeable to solvent
molecules
 Mucous lining of the eye is true semi permeable to boric acid solutions and hence 2
% boric acid solution is isotonic ophthalmic preparation but not RBC

161
 6. Parenteral Admixtures Calculation
Injections / Intravenous Medications :
 are sterile pharmaceutical solutions or suspensions of a drug substance in an

aqueous or nonaqueous vehicle

are administered by needle into almost any part of the body
Injections are packaged in:-
 small volume ampuls or prefilled disposable syringes for single-dose use
 vials & pen-injectors for single- or multiple-dose use
 large volume plastic bags or glass containers for administration by slow
intravenous infusion 162
 Parenteral Admixtures Cont…

 Some injections are available as prepared solutions or suspensions with their drug
contents.
 Others contain dry powder for reconstitution to form a solution or suspension by
adding a specified volume of diluents prior to use.
 Small-volume injections administered as such or used as additives to large-
volume parenteral fluids for intravenous infusion.

163
 Intravenous (IV) Infusions
 Are sterile, aqueous preparations administered intravenously in relatively large
volumes.
 Used to extend blood volume and/or provide electrolytes, nutrients, or medications
 Most intravenous infusions are administered to critical care, infirm, dehydrated, or
malnourished patients, or to patients prior to, during, and/or following surgery.
 Intravenous infusions may be continuous or intermittent.

164
 Intravenous (IV) Infusions Cont…
 Continuous infusions are large volumes of fluid ( 250 to 1000 mL) that run into a
vein uninterruptedly.
 Intermittent infusions are given during scheduled periods.
 Rapid infusion of a medication into a vein is termed IV push is usually conducted
in less than a minute.
 Common Intravenous Infusion Solutions
 Aqueous solutions of dextrose, sodium chloride & lactated Ringer’s solution are
most commonly used intravenous fluids.
 May be administered as such, or with additional drug or nutritional components.
165
 Rate of flow of IV Fluids
 Intravenous fluids must be precisely regulated to ensure adequate hydration of
patients.
 Generally packaging of solution administration equipment will state drop factor
(gtt/mL) that the set delivers.
 Intravenous administration sets are commercially available that deliver 10, 12, 15, 20
& 60 drops per Ml.
 Standard IV solution administration sets deliver 10 gtt/mL
 Blood administration sets deliver 15 gtt/mL
 Microdrop (minidrop) sets deliver 60 gtt/mL
166
 Rate of flow of IV…. Cont
 In the formula method, rate of infusion can be calculated as follows:

 The above formula can be simplified as follows:

Where
 R = rate of flow (gtt/min)

 V= total volume to be infused (in mL)

 D = drip factor (gtt/mL)

167
 T = total time of infusion in minutes
 Rate of flow of IV…. Cont

 large volume parentral solutions are administered by allowing the solution to drip
slowly into a vein by gravity flow or through use of electrical or battery
operated volumetric infusion pumps
 To calculate flow rate of IV infusion (rate of infusion) method of proportion
(involves two steps) or formula method can be used

168
 Calculations of Basic Intravenous Infusions

1. How many grams each of dextrose & NaCl are used to prepare a 250 mL bag of
D5NS for intravenous infusion?
Solution
 250 mL x 0.05 (5% w/v) = 12.5 g dextrose, and
 250 mL x 0.009 (0.9% w/v) = 2.25 g sodium chloride
2. Gentamicin sulfate, 2.5 mg/kg, is prescribed for a 1.5-kg neonate. Calculate (a) the
dose of the drug, (b) the flow rate in mL/minute when the drug is placed in a 50-mL
IV bag if the infusion is to run for 30 minutes.\
7
7|sa\ws7ed7sx84ws4s86468s5z4x 169
 Calculations of Basic Intravenous Infusions
3. An intravenous fluid of 1000 mL of Ringer’s injection was started for a patient at 8: 00 AM
& was scheduled to run for 12 hours. At 3:00 PM it was found that 800 mL of the fluid
remaining in the bottle. At what rate of flow (mL/min) should the remaining fluid be
regulated using IV set that delivers 15 gtt/mL in order to complete the administration of
fluid in the scheduled time?
Solution, Time remaining = 5 hours = 300 minutes
No of gtt/mL = 800 ml x 15 gtt/mL/ 5 hr x 60 min/hr = 40 gtt/min
Flow rate mL/min = 40 gtt/min ÷ 15 gtt/mL = 2.67 mL/min

170
 Intravenous Push (IVP) Drug Administration

 Intended to quickly control heart rate, blood pressure, cardiac output, respiration, or
other life-threatening conditions.
 Safe administration of a drug by IV push depends on precise calculations of dose
and rate of administration.
 Diluted injection rather than a highly concentrated one (e.g., 1 mg/mL versus 5
mg/mL) may be administered as an added safety precaution.

171
 Example Intravenous Push Calculation
1.General guideline in treatment of severe diabetic ketoacidosis include initial bolus
dose of 0.1 to 0.4 unit of insulin/kg IVP, followed by an insulin drip. Calculate the
bolus dosage range for a 220-lb patient
Dosage range = 0.1 unit/kg x 100 kg — 0.4 unit/kg x 100 kg
= 10 unit — 40 unit

172
 Calculation of Reconstitution Dry Powders (IV)

 Certain medication including antiboitics are unstable when stored in solution form

and therefore packed in powder form.

 Dry powders must be reconstituted with a sterile diluents for administration.

 Instruction supplied with the vial state the volume of diluents which should be added

 The powdered drug may or may not contribute to the final volume of the

reconstituted solution.

173
 Reconstitution of Dry Powders for IV
1. A 7.5-g bulk pharmacy vial of cefuroxime (ZINACEF) when constituted with
77 mL of sterile water for injection, contains 375 mg of cefuroxime in each 4
mL.
a. What is the volume of reconstituted solution?
b. What was the volume occupied by dry powder?
Solution
Vrs = 4 mL/375 mg x 7500 mg = 80 mL

Vdp = 80 mL – 77 mL = 3 mL

174
 Parenteral Admixtures
 Parenteral admixtures are combination of one or more drugs to large volume sterile
fluids such as NaCl injection, dextrose injection, lactated Ringer’s injection, and
others.
 The additives are small volume sterile solutions packaged in ampuls, vials, small
volume minibags, or sterile solids, some requiring constitution with a sterile solvent
before transfer.
 Common additives include electrolytes, antibiotics, vitamins, trace minerals,
heparin, and, in some instances, insulin

175
 Example Calculations of Additives to Intravenous Infusion

1.A pharmacist prepared a ‘‘standard concentration’’ of a dopamine HCl solution to

contain 400 mg/250 mL D5W. Calculate the infusion flow rate, in mL/hr, for a 143

lb patient, based on a dose of 50 mcg/kg/minute

Dose = 0.05 mg/kg x 65/min = 3.25 mg/min = 195 mg/hr

Dose in mL/hr = 1 mL/1.6 mg x 195 mg/hr = 121.875 mL/hr

176
 Example Calculations of Additives to Intravenous Infusion

2. A pharmacist receives a medication order for 300,000 units of penicillin G

potassium to be added to 500 mL of D5W. The directions on the 1,000,000-unit vial
state that if 1.6 mL of solvent are added, the solution will measure 2 mL. How many
mL of the solution must be withdrawn and added to the D5W?
Solution
mL of solution to be added = 2 mL/1000000 unit x 300000 unit = 0.6 mL

177
 Calculation of Nutrition
 Provision of nutrients by vein in amounts sufficient to maintain or achieve
anabolism is called total parenteral nutrition (TPN)
 Nutritional energy values are measured in calories
 1 kcal represents amount of heat required to raise the temperature of 1 kg of water
by 1 oC at room temperature

178
 Caloric density of nutritional substrates

 The calories represented by large volume parenterals and TPN products can be calculated as follows:

 Step 1: Find weight in grams of each nutritional substrate in specified volume of solution using following equation:

Grams of nutritional substrate = Volume in mL x Percent expressed as decimal

179
 Calculation of Nutrition

 Step 2: Find the calories represented by each nutritional substrate by multiplying

the weight (gm) with caloric density
 Step 3 : Add up the calories represented by all nutritional substrates in the
preparation
Example 1. How many calories are represented by a liter solution containing 20%
dextrose, 12.5 proteins and 5% fats
1000 mL (0.2 X 3.4 + .125 x 4.10 +0 .05 x 9) = 1000 (0.68+0.5125+ 0.45) = 1000 x
1.6425 = 1642.5 kca

180
 Parenteral Hyperalimentation
 It is large volumes of parenteral fluids containing essential nutrients sufficient to
achieve active tissue synthesis & growth.
 It allows to achieve positive nitrogen balance, weight gain and accelerated wound
healing in adults.
 It contains electrolytes, vitamins, trace elements, antibiotics in large volume dilute
infusion.

181
 Example Calculation of Hyperalimentation

1.A hyperalimentation order for a patient includes 30 mg of amphotericin B, 50 units

heparin, 25 mEq of potassium acetate & 1.5 mg of folic acid to be administered IV
in a litter of D5W over 8 hour period. In filling the medication order, the following
sources are available:
 A vial containing 50 mg of amphotericin B in 10 mL
 A syringe containing 10 units of heparin per mL
 A 20 mL vial of 40 mEq of potassium acetate
 An ampoule containing 5 mg of folic acid per mL
182
 Example Calculation Hyperalimentation Cont…

 How many mL of each additive should be used in filling the medication order?
mLof amphotericin B = 10mL/50 mg x 30 mg = 6 ml
mLof heparin = mL/10 units x 50 unit = 5 mL
mL of potassium acetate = 20mL/40 mEq x 25 mEq = 12.5 mL
mL of folic acid = 1mL/5 mg x 1.5 mg = 0.3 mL

183
 7. Radiopharmaceuticals
Radiopharmaceuticals, or medicinal radiocompounds, are a

group of pharmaceutical drugs which have radioactivity.

Radiopharmaceutical refers to any medicinal or pharmaceutical

product, which when ready for use contains one or more radionuclides
(radioactive isotopes) intended for human use either for diagnosis or
therapy.
Isotopes of an element are nuclides with the same atomic number ‘Z’ but different

mass numbers ‘A’. 184

 Unstable isotopes are distinguished by radioactive transformations & hence
are said to be radioactive.
 The radioactive isotopes of the elements are called radioisotopes or
radionuclides.
 They can be divided into two types: naturally occurring and artificially
produced radionuclides.

185
 Radiopharmaceuticals Cont ….
 The breakdown of an unstable isotope is characterized by radioactivity
 In the process of radioactivity, an unstable isotope undergoes changes until a
stable state is reached, and in the transformation, it emits energy in the form of
radiation.
 The stable state is reached as a result of radioactive decay, which is characteristic
of all types of radioactivity.
 The time required for half the original atoms to decay is called the half-life of
the radioisotope.

186
 Radiopharmaceuticals Cont ….

 N = N0e-λt ….. exponential decay law

 Where N is the number of atoms remaining at elapsed time t, N0 is the number of

atoms originally present (when t = 0), λ is the decay constant for the unit of time in
terms of which the interval t is expressed, and e is the base of the natural logarithm
= 2.71828

 Rate of decay can also expressed by half-life (T1/2)

T1/2 = 0.693
λ

187
 Units of Radioactivity
 Quantity of activity of a radioisotope is expressed in absolute units (total number of
atoms disintegrating per unit time).
 Basic unit is the curie (Ci), which is defined as quantity of a radioisotope in which
3.7 x 1010 (37 billion) atoms disintegrate per second.
 The millicurie (mCi) is one thousandth of a curie & the microcurie (Ci) is one
millionth of a curie.
 The nanocurie (nCi), also known as the millimicrocurie, is one billionth of a curie
(10-9 Ci).

188
 Units of Radioactivity Cont…

 The IS unit for radioactivity is the becquerel (Bq), which is defined as 1

disintegration per second
 Doses of radiopharmaceuticals expressed in megabecquerels as well as in
millicuries and/or microcuries 189
 Calculations of Radioactivity Unit Conversion

1. A thallous chloride Tl 201 injection has a labeled activity of 550 microcuries

(Ci). Express this activity in terms of megabecquerels
550 Ci = 0.55 mCi & 1 mCi = 37 MBq
1 mCi = 37 MBq → 0.55 mCi = 20.35 MBq

190
 Calculations of Half-Life & Disintegration Constant

1.The original quantity of a radioisotope is given as 100 mCi. If the quantity remaining
after 6 day is 75 mCi, calculate disintegration constant & the half-life of the radioisotope
Solution
N = N0 e-tλ this equation can be written in logarithmic form, as:

ln N/N0 = -λt or λ = 2.303/t log N0/N

Substituting the value in place: λ = 2.303/6 log 100/75 →
λ = 2.303/6 (0.125) = 0.05 day-1
t1/2 = 0.693/ λ = 0.693/0.05 = 13.86 day

191
 Calculations of Half-Life & Cont…

2. A sodium phosphate 32P solution contains 1 mCi/mL at the time of calibration. How many
mL of the solution will provide an activity of 500μCi a week after the original assay? The
t1/2 of 32P is 14.3d
Solution
N = N0 e-tλ , by substituting λ = 0.693/ t1/2 , N = N0 e-tλ & e-0.693 = ½
The equation become N = N0 (2-t/t1/2 ); since t/t1/2 = 7/14.3 = 0.49
Then N = 1 (2-0.49)
Solving by logarithms, log N = log 1 - log 2 (-0.49)
log N = 0.1475 → N = 0.71 mCi/mL
mL to give 500 μCi = 1mL/0.71 mCi x 0.5mCi = 0.7 mL

192
• Radiopharmaceuticals administered for diagnostics have very
short half-lives. Technetium-99m (99mTc; the m standing for
metastable), with a half-life of about 6 hours, is used in about 80
percent of nuclear diagnostic procedures.

193
194
End!!!

195