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Pharmaceutical Calculation

By: Tsegaye N. (B. Pharm, MSc)

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Introduction to Pharmaceutical Calculation

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Learning Objectives
After completing of this chapter, students will be able to
 Define pharmaceutical calculation
 Define Sensitivity, Significant Figures, Accuracy and Percentage of Errors
 Determine advantages of studying pharmaceutical calculation, density, specific
gravity, and specific volume using appropriate calculations
 Explain how to measure volume and weight of pharmaceutical preparation.
 Explain the meaning of Roman Numerals and Arabic Numerals
 Convert Roman Numerals to Arabic Numerals
 Convert Arabic Numerals to Roman Numerals
 Describe the procedure for rounding decimals

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Introduction
Definition:
 Pharmacy- the art and science of preparing and dispensing drugs and medicines.
 Drugs are substances that cause a change in a person’s physical and/or
psychological state.
 Pharmaceutics is the discipline of pharmacy that deals with the process of
turning a new chemical entity into a medication to be used safely and effectively
by patients.
 Pharmaceutics deals with the formulation of a pure drug substance into a dosage
form.
 So, it is called science of dosage form design.

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Intro…
 Dosage forms are the means by which drug molecules are delivered to sites of
action within the body.
 Calculation is determining something by mathematical or logical methods.
 Pharmaceutical calculation is the area of study that applies the basic principles
of mathematics to
 Preparation and safe and effective use of pharmaceuticals.

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Advantage of studying pharmaceutical calculation
 Pharmaceutical calculations are essential to the practice of pharmacy within
operational and research areas in
 Industry,
 Academia, and
 Government
 Pharmaceutical calculations use in computation related to;
 Chemical and physical properties of drug substances and pharmaceutical ingredients
 Pharmacodynamics and pharmacokinetics properties;
 Statistical data from basic research and clinical drug studies;
 Pharmaceutical product development and formulation
 Filling prescriptions and medication orders; and etc.
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A step-wise approach toward pharmaceutical calculations

 Success in performing pharmaceutical calculations is based on the following


steps:
1. An understanding of the purpose or goal of the problem;
2. An assessment of the arithmetic process required to reach the goal;
3. Implementation of the correct arithmetic manipulations.

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1.1.Pharmaceutical Measurement

 Pharmaceutical measurement is an important part of pharmacy practice; i.e.


 Accurately weigh,
 Measure volume, and
 Combine individual pharmaceutical components.
It is employed in;
 Community and institutional pharmacies,
 Pharmaceutical research,
 Development and manufacture of pharmaceuticals,
 Chemical and product analysis, and in quality control.

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Pre request mathematical review

A. Numbers and numerals


1.Number
 a total quantity or amount.
 used to count, label, and measure
 It includes numbers like:
 Natural(N) = 0, 1, 2, 3, 4, ... or 1, 2, 3, 4, ...
 Integers(Z) = ..., −5, −4, −3, −2, −1, 0, 1, 2, 3, 4, 5, ...
 Rational(Q) = a/b where a and b are integers and b ≠ 0
 Real (R) = include all of the measuring numbers, and etc .

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Cont…
Numbers can be presented in concrete or abstract form.
1.Abstract (pure)number
A number by itself without application to anything.
E.g., 2, 4, 3, etc.
2.Concrete numbers
A number that designates a quantity of objects by units of measurement.
E.g., 4mg, 7mL, …

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Cont…
2.Numerals
 a word, sign or group of words or signs representing a number.
 Types;
1.Arabic numerals
Numeral system in use today based on the ten digits.
 Commonly used universally to indicate quantities because of it is easy to read and not
confusing.
 Represented by zero and nine digits(1-9)
 0, 1, 2, 3, 4, 5, 6, 7, 8, 9

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Cont…

2.Roman numerals
Numeral system based in ancient Rome that uses letters and combinations of
letters used to designate numbers.
 Eight(8) letters of alphabets (either lowercase or uppercase) used
 Not used in computation but merely used for counting.

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Cont…
Roman numerals Arabic numerals
ss 1/2
I(i) 1
V(v) 5
X(x) 10
L(l) 50
C(c) 100
D(d) 500
M(m) 1000
NB. ‘ss’ used with lowercase to represent ‘half’.

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Cont…
Rules to use Roman numerals
A. When roman numeral is
 Repeated, doubles its value.
 E.G., Xx = 10+10 =20
 Repeated three times, triple its value.
 E.G., Xxx =3 x10 =30
B. When roman numeral(s) of lesser value follows one of greater value, they are
added.
E.g., xvi =10+5+1 = 16
C, When roman numeral(s) of lesser value precedes one of greater value, they are
subtracted from the greater value numeral.
E.g., ix =10-1=9

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Cont…
D, When roman numeral of lesser value is placed between two greater values, it is
first subtracted from greater numeral after it.
E.g., CLXIV = 100+50+10+(5-1)
= 164
E, Roman numeral should not be repeated more than three times in succession
rather largest value should be used.
 E.g. not as ’vvvv’ rather ‘xx’ to represent ‘20’.
 Use ‘IV’ to represent 4 than ‘IIII’.

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Cont…
 A. Converting Arabic numerals to Roman numerals
 Example: Convert 1984 to Roman Numerals.
Soln; 1984 =1000 + 900 + 80 + 4
= M + CM + LXXX + IV
So,1984 = MCMLXXXIV
 Example: convert 2098 to Roman Numerals.
Soln; 2098 = 1000 + 1000 + 90 + 8
=M + M + XC + VIII
= MMXCVIII

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Cont…

 B.Converting Roman numerals to Arabic numerals


E.g. Convert DCCC to Arabic Numerals.
Soln;
DCC = 500 + 100 + 100
= 800
E.g. Convert LXVII to Arabic Numerals.
Soln;
LXVII = 50 + 10 + 5 + 2
= 67

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B. Balance sensitivity, Significant Figures, Accuracy and Percentage
of Errors
 Instrument manufacturers usually supply specifications for their equipment that
define its accuracy, precision and sensitivity
1. Accuracy
How close a measured value is to the actual (true) standard value.
2. Precision
It is how close the measured values are to each others.
E.g. if the weight of the tablet measured many times and the values are close together;
then, it has a high degree of precision or repeatability.
The values do not have to be the true value rather just grouped together

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Cont…
3. Sensitivity
The smallest absolute amount of change that can be detected by a measurement.
A balance is said to be sensitive when it can register small differences in weight.
4. Percentage of error
Measuring instruments are not exact!
When a pharmacist measures a volume of liquid or weight of a material, two
quantities become important:
(1) The apparent(desired) weight or volume measured, and
(2) The possible excess or deficiency in the actual quantity obtained.
So, to recognize the limitations of the instruments used and the magnitude of the
errors; you can use percentage error.
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Cont…
Percentage of error
 Show the error as a percent of the exact value
 Is all about comparing a guess or estimate to an exact value.
 The maximum potential error multiplied by 100 and divided by the quantity desired.
Formulated as follows:
Percentage of error
= |Approximate Value - Exact Value| × 100%
|Exact Value|
= | Error | * 100%
Quantity desired

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Cont…
For example,
 Prescription calls for 800 mg of a substance. After weighing this amount on a
balance, the pharmacist decides to check by weighing it again on a more
sensitive balance, which registers only 750 milligrams. Because the first
weighing was 50 milligrams short of the desired amount, what was the
percentage of error?
 Solution;
Given;
quantity desired = 800mg,
Error = |750mg-800mg| = 50mg
Answer;
percentage of error = 50 mg x 100%
800 mg
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6.25%
Cont…
5.Significant figures
 All measurements are approximations—no measuring device can give perfect
measurements without experimental uncertainty.
 When we record a measurement the last figure to the right must be taken to be
an approximation.

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Cont…
E.g.
The number 573.4grams interpreted as
 5 = 500 grams neither more or less
 7 = 70 grams neither more or less
 3 = 3 grams neither more or less
 but the final 4 means approximately 0.4grams (plus or minus
some fraction of a gram).

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Cont…

 Significant figures are consecutive figures that express the value of a denominate
number accurately enough for a given purpose.
 Simply the number of figures that are known with some degree of reliability.
 The number of significant figures indicates the degree of accuracy that is
sufficient for a given purpose.
 The accuracy varies with the number of significant figures; which are all absolute
in value except the last figure to the right must be taken to be an approximation,
and this is properly called uncertain.

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Cont…
 The interpretation of zero
Whether zero is significant, however, depends on its position.
1, Digits(0-9) other than zero are significant.
 E.g. 12.5g has 3 significant figure.
2, Zeros appearing any where between digits is significant.
E.g.
 102.56 mL has 5 significant figure.
 8.0054g has 5 significant figure

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Cont…
3, Trailing zeros after a decimal point are always significant; b/c, it contributes to
the value of the number.
E.g. a, 0.06050 has 4 significant figure.
b, 998.100 has six significant figure
The significance of trailing zeros in a number not containing a decimal point or
before a decimal point can be ambiguous.
E.g. The number of significant figures in number like 50,600 calories may be 3, 4
or 5(uncertain).
 B/c one doesn’t know whether these zeros are meant to be significant or simply to
indicate the magnitude of the number.

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Cont…
 The potential ambiguity in the significance of trailing zeros can be avoided by the
use of standard exponential or scientific notation.
For example, depending on whether the number of significant figures is 3, 4,
or 5, we would write 50,600 calories as:
 5.06 × 104 calories (3 significant figures)
 5.060 × 104 calories (4 significant figures), or
 5.0600 × 104 calories (5 significant figures).
5, Zeros used only to show the location of the decimal point i.e. zeros before the
first non-zero digit(leading zeros) are not significant.
E.g. 0.005=1 significant figure.

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Rounding and Rules for rounding a measurement

 Rounding decimals : -
 A process to eliminate unnecessary decimal numbers
 Used when an instrument hasn’t the capability to weigh precisely all the quantities.
Rules for rounding measurement
a) When rounding a measurement, retain as many figures as will give only one
uncertain figure.
b) When eliminating superfluous(excess) figures following a calculation,
add 1 to the last figure retained in a calculation if it is 5 or more.
 For example, 2.46 should be rounded off to 2.5 but, 2.43 should be rounded off to
2.4
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Cont…

c. When rounding to given number of decimal places, count only those


places after the decimal point.
E.g. Round 34.1362 to two decimal places.
Answer. b/c of it has 4 decimal place and 6>5, round it to
= 34.14

d. When rounding to a given number of significant figures, begin


counting from the first non-zero digit.
E.g. round 34.13620 to 5 significant figure.
Answer. = 34.136

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Cont…

e. When multiplying or dividing two approximate numbers, retain no more


significant figures than the number having the fewest significant figures.
For example, 0.049623 x 32.0 / 478.8 = 0.003316
answer may be rounded to 0.00332

f. In +/- approximate numbers, include only as many decimal places as are in with
the fewest decimal places.
E.g. 21.398 + 405 - 2.9 = 423.498
answer may be rounded to 423

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Cont…

g) When multiplying or dividing an approximate number by an absolute number,


the result should be rounded to the same number of significant figures as in the
approximate number.
For example,
1.54 mg x 96= 243.84 mg;
Answer may be rounded to 244 mg, or to three significant figures.

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Measurement Volume and Weight

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Measurement of volume and weight
 Measurement is finding a number that shows the size or amount of something.
 We can measure many different things, but most often we measure length, area,
volume, mass and time.
 Each instrument used must meet established standards for sensitivity, accuracy,
and capacity.
 Volume is the amount of space an object takes up or contains.
 Instruments used for measurement of volume ranges from micro pipettes and
burettes to calibrated vessels.
 In pharmacy practice, the most common instruments for measuring volume are
cylindrical and conical (cone-shaped) graduates.
 This graduate can be prepared from glass or plastics.

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Cont…..…
 For measurement of small volumes we use;

e
ring
d sy

te
ret
rate

bu
b
Cali

tte
Pipe
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Pharmaceutical Calculation
Cont’d…
Liter is the primary unit / (SI) of volume.

Liter =10 (dl)

=100 cl

=1000mL(cc)

=1,000,000µm

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B. Measurement of weight

The weight is how much something is pulled by gravity.


Balances and scales are weight-measuring instruments.

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Cont’d…
 The primary unit of weight in the SI is the gram(g).
1g
= 0.001 kilogram(kg)
=10 decigrams(dg)
=100 centigrams(cg)
=1000 milligrams(mg)
=1,000,000 micrograms(mcg)

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Aliquot method of weighing and measuring

When a degree of precision in measurement that is beyond the capacity of the


instrument at hand is required, the pharmacist may achieve the desired precision
by calculating and measuring in terms of aliquot parts.
 Uses to achieve the desired precision; when a degree of precision in measurement is
beyond the capacity of the instrument at hand is required.

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Cont….…

The aliquot method of weighing:-


 Is a method by which small quantities of a substance beyond the capacity of the
instrument obtained within the desired degree of accuracy.
It is done by steps ;
1. weighing a larger-than-needed portion of the substance,
2. diluting it with an inert material, and then
3. weighing a portion (aliquot) of the mixture calculated to contain the desired
amount of the needed substance.

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Cont……

Preliminary Step.
 The smallest quantity of a substance that can be weighed on the balance with the
desired precision

= Sensitivity Requirement (mg) x100%


Acceptable Error (%)

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Sensitivity Requirement

The load that will cause a change of one division on the index plate of the
balance.
May be determined by the following procedure:
1. Level the balance.
2. Determine the rest point of the balance.
3. Determine the smallest weight that causes the rest point to shift one division on
the index plate.

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Cont’d…
Example;
 On a balance with an SR of 6mg, and with an acceptable error of not greater
than 5%, 5 mg of a drug substance is required on a prescription. By this balance,
a) Calculate the smallest quantity of a substance that can be weighed with the desired
precision?
b) How much quantity must be weighed for the desired accuracy?

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Cont…..…
Given: SR=6 mg
A.e = 5%, Quantity required = 5mg
Requirements,
a. smallest quantity measurable by this balance
b. quantity must be weighed for the desired accuracy
Soln;
a.Sq = SR x 100% Acceptable error
= 6mg x 100% 5% = 120 mg

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Cont…..…

b. step 1, Select a multiple of the desired quantity that can be weighed with the
required precision (>120mg).
= 5mg x y > 120mg
= y >24
Let, 25 x 5mg=125mg should be weighed

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Cont…..…
Step 2. Dilute the multiple quantity with an inert substance
 The amount of inert diluent to use is determined by the fact that the aliquot
portion of the drug-diluent mixture weighed in Step 3 must be equal to or
greater than the minimum weighable quantity previously determined(120mg).
 If we decide on 120 mg for the aliquot portion in Step 3, multiply it by the
multiple selected in Step 1 (i.e., 25), 3000 mg for the total quantity of the drug-
diluent mixture to prepare.
 Subtracting the 125 mg of drug weighed in Step 1, we must add 2875 mg of
diluent to prepare the 3000 mg of drug-diluent mixture.

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Cont…..…

Step 3. Weigh the aliquot portion of the dilution that contains the desired quantity.
Since 25 times the needed amount of drug substance was weighed (Step 1), an
aliquot part equal to 1⁄25 of the 3000-mg drug-diluent mixture, or 120 mg, will
contain the required quantity of drug substance.
proof:1⁄25 x 125 mg (drug substance weighed in Step1) = 5 mg
 1⁄25 x 2875 mg (diluent weighed in Step 2) =115 mg
 120 mg aliquot part

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Cont’d…

 Eg.2. A torsion prescription balance has a sensitivity requirement of 6.5


milligrams. Explain how you would weigh 15 milligrams of atropine sulfate with
an accuracy of 5%, using lactose as the diluent.
Answer: Smallest quantity to weigh

= SR x 100% A.e

= 6.5mg x 100% 5%

= 130mg

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Cont’d…

If 10 is chosen as the multiple, and if 130 milligrams is set as the weight of the
aliquot, then:
 1. Weigh 10 x 15 mg = 150 mg of atropine sulfate
 2. Dilute with 1150 mg (1300-150) of lactose to make 1300 mg of dilution
 3. Weigh 1⁄10 of dilution, or 130 mg, which will contain 15 mg of atropine sulfate.

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Density, Specific Gravity and Specific Volume

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A. Density (d)

 How many particles there are in a given amount of space(volume).


Density =

 usually expressed as grams per cubic centimeter (g/cc)

 Water is 1 g/cc; b/c of the gram is defined as the mass of 1 cc of water at 4 oc.

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Cont…

For example,

If 10 mL of sulfuric acid weighs 18 g, its density is:

Density = mass/volume

=18 g/10 mL = 1.8g/mL

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B. Specific gravity

 Comparison of weights of equal volumes


 Calculated by dividing or ratio of the weight of a given substance by the weight
of an equal volume of water (i.e. both substances at the same temperature)
 Water is used as the standard for the specific gravities of liquids and solids; and
the most useful standard for gases is hydrogen.

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Cont…
Specific gravity
= Wt. of substance Wt. of equal volume of water
The specific gravities of water at 25 0c is 1.00
Substances that have a specific gravity less than one are lighter than water.
Substances that have a specific gravity greater than one are heavier than water.

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Cont…
Application of specific gravity
 Specific gravity is an indicator of both the concentration of particles in the urine
and a patient’s degree of hydration.
 A higher-than-normal specific gravity indicates that the urine is concentrated.
 Specific gravity is a factor that expresses how much heavier or lighter a substance
is than water.

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Cont…
E.g.1
If 10 mL of sulfuric acid weighs 18g, and 10 mL of water, under similar
conditions, weighs 10 g, calculate specific gravity of the acid.
Soln;
Specific gravity
= Wt of H2SO4/Wt of H2O at similar condition (T $ P)
= 18g/10g =1.8

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Cont’d…
E.g.2
A specific gravity bottle weighs 23.66 g. When filled with water, it weighs 72.95
g; when filled with another liquid, it weighs 73.56 g.
What is the specific gravity of the liquid?
Soln; Wt of the liquid = 73.56 g - 23.66 g = 49.90 g

Wt of water = 72.95 g - 23.66 g = 49.29 g

Specific gravity of the liquid


= Wt of the liquid/ Wt of water

= 49.90 (g)/49.29 (g)


=1.012
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Cont…
 If the volume of the liquid in question is assumed to be the same volume as that
of water for which milliliter equals to gram;
Grams (other liquid) = Grams (of equal volume of water) x Specific gravity (other
liquid)
Milliliters = Grams Specific gravity

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Cont…
E.g. 1
 What is the weight, in grams, of 3620 mL of alcohol with a specific gravity of
0.820?
 Soln
= 3620 mL of water weigh 3620 g
= Weight of alcohol = grams of H20 x Sp.g of alcohol
= 3620 g x 0.820
= 2968 g, answer.

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Cont…
E.g. 2
What is the volume, in milliliters, of 492 g of nitric acid with a specific gravity of 1.40?
soln;
Grams HNO3 = Grams (of equal volume of water) x Sp.g. of HNO3
Grams (of equal volume of water) = Grams HNO3 / Sp.g. of HNO3
= 492 g/ 1.4 = 351 g
351 g of water measure 351 mL and equals with that HNO 3 volume.
So, HNO3 volume is 351mL.

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Density vs. Specific gravity

Density Specific gravity

 Concrete(definite) number  ratio of like quantities,

 an abstract (theoretical) number.

 varies with the units of measure  a constant value for each substance per
used, controlled condition, b/c of no
dimension.

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C. Specific Volume
 Comparison of volumes of equal weights.
 The volume of a substance to the volume of an equal weight water taken as a
standard, both having the same temperature.
 Specific volume = volume of a substance /volume of an equal weight H2O
 Reciprocals to specific gravity = 1/specific gravity
 An abstract number representing the ratio.
E.g. Calculate the specific volume of a syrup, 91.0 mL of which weighs 107.16 g.
107.16 g of water measures 107.16 mL
Soln:
Specific volume of syrup = 91.0 (mL)/107.16 (mL)
= 0.849
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Cont…
E.g.2
What is the specific volume of phosphoric acid having a specific gravity of 1.71?
Soln;
specific volume = 1/specific gravity
= 1/1.71
= 0.585

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o u
k y
a n ?
h
T Q ??

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Percentage calculations

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Objectives

Upon successful completion of this chapter, the student will be able to:
 Define the expressions percent weight-in-volume, percent volume-in -volume, and
percent weight in-weight.
 Define the expression ratio strength.
 Convert percent strength to ratio strength and ratio strength to percent strength.
 Calculate the percentage strength and ratio strength of a pharmaceutical preparation.
 Apply percent strength and ratio strength to calculate the quantity of an ingredient
present in a pharmaceutical preparation.
 Apply percent strength and ratio strength to calculate the quantity of an ingredient to
use in compounding a pharmaceutical preparation
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Percentage, ratio and proportion
Percentage(%)
 The term percent mean ‘‘by the hundred’’ or ‘‘in a hundred,’’ and percentage
means ‘‘rate per hundred’’
 A percent may also be expressed as a ratio, represented as a common or decimal
fraction.
Ratio
 The relative magnitude of two quantities or numbers
 The terms of a ratio must be of the same kind
Proportion
 Is the expression of the equality of two ratios.
A/b = c/d

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Cont…
 Product of means = product of extremes
 a:b = c:d
 b×c=a×d
Examples:
1. If 3 tablets contain 975 milligrams of aspirin,
a) How many milligrams should be contained in 12 tablets?
b) How many tablets should contain 3900 milligrams?
Proportions are frequently used to calculate drug doses in pharmacy.

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Cont…
Use the ratio-proportion method any time one ratio is complete and the other is
missing a component.
1. Calculate the proportion by placing the ratios in fraction form so that the
unknown is in the upper-left corner.
2. Check that the unit of measurement in the numerators is the same and the unit of
measurement in the denominators is the same.
3. Solve for unknown by multiplying both sides of the proportion by the
denominator of the ratio containing the unknown, and cancel.
4. Check your answer by seeing if the product of the means equals the product of
the extremes.

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Percentage preparations
 The percentage concentrations of active and inactive constituents in various types
of pharmaceutical preparations are defined as follows by the United States
Pharmacopeia:
 Percent weight-in-volume(w/v)
 Expresses the number of grams of a constituent in 100 ml of solution or liquid
preparation,
 Is used regardless of whether water or another liquid is the solvent or vehicle.
 Expressed as: ____% w/v.

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Cont…
Percent volume-in-volume(v/v)
 Expresses the number of milliliters of a constituent in 100 ml of solution or
liquid preparation.
 Expressed as: ____% v/v.
Percent weight-in-weight(w/w)
 Expresses the number of grams of a constituent in 100 g of solution or
preparation.
 Expressed as: ___% w/w.

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Cont…
The term percent , or symbol, %, when used without qualification means:
 For solutions or suspensions of solids in liquids, percent weight-in-volume;
 For solutions of liquids in liquids, percent volume-in-volume;
 For mixtures of solids or semisolids, percent weight- in-weight;
 For solutions of gases in liquids, percent weight-in-volume.

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Cont…
 In general, the nature of the ingredients in a pharmaceutical preparation
determines the basis of the calculation.
 A powdered substance dissolved or suspended in a liquid vehicle would
generally be calculated on a weight-in-volume basis;
 A powdered substance mixed with a solid or semisolid, such as an ointment
base, would generally be calculated on a weight in-weight basis.
 A liquid component in a liquid preparation would be calculated on a volume-
in-volume basis.

04/09/2024 Pharmaceutical Calculation 72


Cont…
 In most instances, use of percentage concentrations in the manufacture and
labeling of pharmaceutical preparations is restricted to instances in which the dose
of the active therapeutic agent (ATI) is not specific.
 For example, in ointments, lotions, external solutions, and similar products may
commonly be expressed in percent strength (e.G., A 1% hydrocortisone ointment).
 In most dosage forms, such as tablets, capsules, injections, oral solutions, and
syrups, among others, the amounts of ATIs are expressed in definitive units of
measure, such as milligrams per capsule, milligrams per milliliter, or other terms.
 On the other hand, in many pharmaceutical formulations, pharmaceutical components
such as flavoring agents, solvents, excipients, preservatives, and so on, may be
expressed in terms of their percentage concentration

04/09/2024 Pharmaceutical Calculation 73


Percentage weight-in-volume
 In a true expression of percentage(i.E., Parts per one hundred parts),
 The percentage of a liquid preparation(e.G., Solution, suspension, lotion, etc.) Would
represent the grams of solute or constituent in 100 g of the liquid preparation.
 A different definition of percentage for solutions and for other liquid preparations:
 Represent grams of a solute or constituent in 100 ml of solution or liquid preparation.
 The "correct" strength of a 1% (w/v) solution or other liquid preparation is defined as
containing 1 g of constituent in 100 ml of product.

04/09/2024 Pharmaceutical Calculation 74


Examples
1. How many grams of dextrose are required to prepare 4000 mL of a 5%
solution? =200mg
2. How many grams of aminobenzoic acid should be used in preparing 8
fluidounces(8*29.57mL) of a 5% solution in 70% alcohol? =11.83g
3. How many grams of potassium permanganate should be used in compounding
the following prescription? 0.0002*250g =0.05g
Potassium Permanganate 0.02%
Rx Purified Water ad 250.0 mL
Sig. As directed

04/09/2024 Pharmaceutical Calculation 75


Percentage volume-in-volume
 The percentage strength indicates the number of parts by volume of the active
ingredient contained in the total volume of the solution or liquid preparation
considered as 100 parts by volume
Example:
1. In preparing 250 mL of a certain lotion, a pharmacist used 4 mL of liquefied
phenol. What was the percentage (v/v) of liquefied phenol in the lotion?
250/4=100/x =1.6%
2. Peppermint spirit contains 10% (v/v) of peppermint oil. What volume of the
spirit will contain 75 mL of peppermint oil? 10/100 =75/x =750mL

04/09/2024 Pharmaceutical Calculation 76


Percentage weight-in-weight
 True percentage or percentage by weight
 Indicates the number of parts by weight of active ingredient contained in the total
weight of the solution or mixture considered as 100 parts by weight.
 Liquids are not customarily measured by weight.
 Therefore, a weight-in-weight solution or liquid preparation of a solid or a
liquid in a liquid should be so designated: e.g., 70% (w/w).

04/09/2024 Pharmaceutical Calculation 77


Examples
1. How many grams of phenol should be used to prepare 240 g of a 0.5% (w/w)
solution in water?=240g*0.05=12g
2. How many grams of a drug substance are required to make 120 mL of a 20%
(w/w) solution having a specific gravity of 1.15? =120g*(1.15/1mL)
*(20%/100%)=27.6g
3. How many grams of a drug substance should be added to 240 mL of water to
make a 4 % (w/w) solution?
 100% -4%=96%
 96/4=240/x=10g

04/09/2024 Pharmaceutical Calculation 78


Ratio strength
 The concentration of weak solutions or liquid preparations is frequently expressed
in terms of ratio strength.
 is merely another way of expressing the percentage strength of solutions or liquid
preparations (and, less frequently, of mixtures of solids).
 For example, 5% means 5 parts per 100 or 5:100.
 Although 5 parts per 100 designates a ratio strength, it is customary to
translate this designation into a ratio, the first figure of which is 1; thus, 5:100
= 1: 20

04/09/2024 Pharmaceutical Calculation 79


Cont…
 The ratio and percentage strengths of any solution or mixture of solids are
proportional, and either is easily converted to the other by the use of proportion.
 Ratio Strength Given Percentage Strength
 Express 0.02% as a ratio strength=0.02/100=1:500
 Percentage Strength Given Ratio Strength
 Express 1: 4000 as a percentage strength =1/4000=0.025%

04/09/2024 Pharmaceutical Calculation 80


NOTE:
 To change ratio strength to percent strength, it is sometimes convenient to
"convert" the last two zeros in a ratio strength to a percent sign (%),
 Change the remaining ratio to a common fraction, and then to a decimal fraction
in expressing percent
 Examples:
 1:100 =1/1% = 1%
 1:200 = ½% = 0.5%
 3:500 = 3/5% = 0.6%

04/09/2024 Pharmaceutical Calculation 81


Examples:
1. A certain injectable contains 2 mg of a drug per milliliter of solution. What is
the ratio strength (w/v) of the solution?
0.002g/ml=1:500
2. What is the ratio strength (w/v) of a solution made by dissolving five tablets,
each containing 2.25 g of sodium chloride, in enough water to make 1800 mL?
ans=1:160
3. How many grams of potassium permanganate should be used in preparing 500
mL of a 1:2500 solution?
Ans = 2500/500=0.2g
4. How many milligrams of hexachlorophene should be used in compounding the
following prescription?
0.25%*10g=25mg
 Hexachlorophene 1:400
 Hydrophilic Ointment ad 10 g
 Sig. Apply.
04/09/2024 Pharmaceutical Calculation 82
Conversions of concentration to "mg/mL"
 In patient care settings, need to convert rapidly product concentrations expressed
as percentage strength, ratio strength, or as grams per liter (as in IV infusions) to
milligrams per milliliter (mg/mL).
 To convert product percentage strengths to mg/mL, multiply the percentage
strength, expressed as a whole number, by 10.
 Example: Convert 4% (w/v) to mg/mL.
 To convert product ratio strengths to mg/mL, divide the ratio strength by 1000.
 Example: Convert 1:10,000 (w/v) to mg/mL.

04/09/2024 Pharmaceutical Calculation 83


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

 The strengths of very dilute solutions are commonly expressed in terms of parts
per million (ppm) or parts per billion (ppb),
 i.e., the number of parts of the agent per 1 million or 1 billion parts of the
whole.
 Fluoridated drinking water, used to reduce dental caries, often contains 1 part
of fluoride per million parts of drinking water (1:1,000,000).
Example:
 Express 5ppm of iron in water in percent strength and ratio strength.

04/09/2024 Pharmaceutical Calculation 84


Calculation of doses and formulas

04/09/2024 Pharmaceutical Calculation 85


Learning Objectives
 Upon successful completion of this chapter, the student will be able to:
 Differentiate between the 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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Definition of dose
The dose of a drug is : -
The quantitative amount of drug administered or taken by a patient for the
intended medicinal effect.
Expressed as;
 A single dose: the amount taken at one time
 A daily dose: the amount taken per day, or
 A total dose: the amount taken during the course of therapy.

04/09/2024 Pharmaceutical Calculation 87


A daily dose :
 May be subdivided and taken in divided doses,
 Two or more times per day depending on the characteristics of the drug and the
illness.
The schedule of dosing {e.g., four times per day for 10 days) is referred to as the
dosage regimen.

04/09/2024 Pharmaceutical Calculation 88


Cont…
 Drug doses vary greatly between drug substances; some drugs have small doses,
other drugs have relatively large doses.
 The dose of a drug is based on;
Drug factors Patient factors
Biochemical and pharmacologic Age,
activity, Body weight,
Physical and chemical properties, Surface area,
Dosage form used, Liver and kidney function (for drug
Route of administration metabolism and elimination), and
The severity of illness.

04/09/2024 Pharmaceutical Calculation 89


Dose measurement
 Doses are measured and administered by professional and paraprofessional
personnel.
 A variety of measuring devices may be used. Such as;
s
on

s
s

ge
o

on
asp

ri n

ups
spo

Sy
Te

dc
bl e

ate
Ta

libr
Ca
04/09/2024 Pharmaceutical Calculation 90
The drop as a unit of volume measure
The drop (abbreviated gtt):
 Is used as a measure for small volumes of liquid medications.
A drop does not represent a definite quantity, because drops of different liquids
vary greatly.

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Cont…
 Accordingly, the official dropper is calibrated as when held vertically, it delivers
water in drops, each of which weighs between 45 and 55 mg.
 It deliver approximately 20 drops of water per milliliter
 i.e., 1 mL of water = 1 gram or
 1000 mg ÷ 50 mg [ave.]/drop ≅ 20 drops).
 The dropper may be calibrated by counting the 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(e.g., 20 drops/mL).

04/09/2024 Pharmaceutical Calculation 92


Cont…
E.g. if a pharmacist counted 40 drops of a medication in filling a graduate cylinder
to the 2.5-mL mark, how many drops per milliliter did the dropper deliver?
Sol/n;
40drops = 2.5mL
X drops = 1mL
40 drops x 1mL = xdrops x2.5mL
X= 16 drops/mL

04/09/2024 Pharmaceutical Calculation 93


Calculation of doses
A pharmacist often needs to calculate
 The size of a dose,
 The number of doses, or
 The total quantity of medication to dispense.
Number of doses = Total quantity/Size of dose
 In this equation, the units of weight or volume must be the same for the total
quantity and size of the dose.

04/09/2024 Pharmaceutical Calculation 94


Cont….…
Examples
1. If the dose of a drug is 200 mg, how many doses are contained in 10 g?
Sol/n;
total quantity = 10g = 10,000mg
dose size = 200mg;
Dose no = 10,000mg/200mg = 50 doses

04/09/2024 Pharmaceutical Calculation 95


Cont…
2. How many teaspoonful would be prescribed in each dose of an elixir if 180 mL
contained 18 doses?
Sol/n;
total quantity = 180 mL
no of dose = 18
Size of dose = total quantity =
dose no
= 180 mL
18
= 10 mL = 2 teaspoonful

04/09/2024 Pharmaceutical Calculation 96


Cont……
3.If 0.050 g of a substance is used in preparing 125 tablets, how many micrograms
are represented in each tablet?
Sol/n;
0.050 g = 50 mg = 50,000 mcg
50,000mcg/125tablets = y mcg/1tablet,
y = 400mcg

04/09/2024 Pharmaceutical Calculation 97


Patient related factors determining dose
 The pharmacist is much concerned with the maximum limit of the doses which, if
exceeded, may cause untoward effects in the patient.
 The actual dose of a drug is to be decided by the prescriber depending on patient's
age, body surface area
sex, severity of illness
Body weight, route of administration etc.

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Cont…

A. Drug Dosage based on Age (pediatrics and geriatrics)


 The adjustment of dosing and dosage regimen in children and elder needs special
consideration due to different changes like; change in pharmacokinetics
parameters, age, body weight, surface area and etc.
 The age of the patient is a consideration in the determination of drug dosage; b/c
of the physiologic differences between different age groups.

04/09/2024 Pharmaceutical Calculation 99


Cont..…
I. Pediatric patient
 From birth through adolescence(17yrs).
 Dose adjustment for pediatrics needed; b/c of underdeveloped;
 Biologic functions such as respiration and circulation, and
 Body systems for drug metabolism (e.G. Liver enzymes) and drug elimination
(e.G., Renal system).

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Cont…
 Various rules of dosage in which the pediatric dose was a fraction of the adult
dose, based on relative age
Young’s rule
Dose for child = Age(yrs.)/[Age(yrs.) + 12] x Adult dose
Cowling’s rule:
 Dose for child = [Age at next birthday (in yrs.)/24] x Adult dose
 Today, these rules are not in general use; b/c, age alone is no longer considered a
singularly valid criterion in the determination of accurate dosage for a child .

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Cont.…

Example
 Calculate the dose of valium of a 13months old child by the Young’s rule, if the
adult dose is 10mg. Valium is available as 5mg/5mL.
Soln
Dose for child = Age(yrs.)/ [Age(yrs.) + 12] x Adult dose
= [13/12] / [13/12+12] x 10mg
= 0.83mg
5mg/5mL = 0.83mg/0.83mL

04/09/2024 Pharmaceutical Calculation 102


Cont…

II. Geriatric patient


Geriatric medicine or geriatrics is the field that concerned with the promotion of
health and the treatment and prevention of disability and disease in old
age(>65years).
The functional capacities of most organ systems decline throughout adulthood(17-
45 years), and important changes in drug response occur with advancing age.

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Cont….…
Example:
 The adult dose of a drug is 500 mg every eight hours. For an elderly patient with
impaired renal function, the dose is reduced to 250 mg every 6 hours. Calculate
the reduction in the daily dose, in milligrams.
Soln; daily dose for
 a, adult = 500mg x 3(every 8hrs.) = 1500mg
 b, elder = 250mg x 4(every 6hrs.) = 1000mg
reduction in daily dose = [1500 – 1000]mg = 500mg

04/09/2024 Pharmaceutical Calculation 104


Cont……
B. Drug Dosage calculation based on Body Weight
 Common in children and obese patients.
 The volume of distribution of drug is the function of the total body water and
extracellular fluid(ECF) which in turn are related to body weight.
 The doses of the majority of drugs based on body weight are conveniently
expressed in terms of mg/kg.

04/09/2024 Pharmaceutical Calculation 105


Cont….…
A useful equation for the calculation of dose based on body weight is:
Patient’s dose (mg)
= Patient’s weight (kg) x Drug dose (mg)/1(kg)

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Cont…..…
 When the percent of fat is greater, the ECF is less. Therefore,
 There is less distribution of polar drugs.
 As a result, the plasma concentration of polar drugs will be higher and there may be
a need to a dose of such drugs.
 Nonpolar/ lipid soluble drugs distribution in cellular tissues will be more and there
may be a need to increase a dose of such drugs.

04/09/2024 Pharmaceutical Calculation 107


Cont……
Example
 The usual initial dose of chlorambucil is 150 mcg/kg of body weight. How many
milligrams should be administered to a person weighing 93 kg?
Sol/n:
150 mcg = 0.15 mg
Patient’s dose (mg)
= patient’s weight (kg) x drug dose (mg)/1 (kg)
= 93kg x 0.15mg/kg = 13.95mg

04/09/2024 Pharmaceutical Calculation 108


Cont……
C. Drug Dosage based on Body Surface Area
Widely used for two types of patient groups:
 Cancer patients receiving chemotherapy and
 Pediatric patients, with the general exception of neonates, who are usually dosed on a
weight basis with consideration of age and a variety physiological factors.

04/09/2024 Pharmaceutical Calculation 109


Cont….…

 BSA (m²) = ([Height(cm) x Weight(kg)] 3600 )½


 Patient’s dose = [Patient’s BSA (m2)/1.73 (m2)] x Drug dose (mg)
Example
 If the adult dose of a drug is 100 mg, calculate the approximate dose for a child
with a BSA of 0.83 m2.
Soln,
Child’s dose = [0.83 m2/1.73 m2] x 100 mg
= 47.97 or 48 mg,

04/09/2024 Pharmaceutical Calculation 110


Enlarging and reducing formulas

04/09/2024 Pharmaceutical Calculation 111


Enlarging and reducing formulas
 Pharmacist may enlarge or reduce formula for pharmaceutical preparation in the
course of their professional practice or manufacturing activities to satisfy the
needs of your pharmacy.
 Reducing or enlarging a pharmaceutical formula is a process by which the total
quantity is changed while the correct proportion of one ingredient to the other is
maintained.
 Components of formulation are expressed in units of weight or volume (usually
metric) or in proportion parts.

04/09/2024 Pharmaceutical Calculation 112


Cont..…
 Each ingredients in a pharmaceutical formula relates proportionally to each of the
other ingredients.
 If quantity of one is changed, so must the quantity of all other.
 In reducing/ enlarging formula, only the numerical value of each ingredient is
changed; and it doesn’t matter whether the units of individual ingredients are
alike or different.

04/09/2024 Pharmaceutical Calculation 113


Cont….
 Calculation to reduce or enlarge formulas may be performed by a two step
process:
Step 1,
 Using the following equation, determine the factor that defines the multiple or
decimal fraction of the amount of formula to be prepared:
Factor = Quantity of formula desired
Quantity of formula given

04/09/2024 Pharmaceutical Calculation 114


Cont….
A factor greater than 1 represent the multiple of the formula.
Factor less than one indicates the fraction of the formula to be prepared.
Step. 2
Multiply the quantity of each ingredient in the formula by the factor
This determines the amount of each ingredient required in the reduced or
enlarged formula

04/09/2024 Pharmaceutical Calculation 115


Cont’d…
Cont’d…
Example;
If a formula for 1000ml contains 6 g of a drug, how many grams of
drug are needed to prepare 60ml of the formula?
Step 1
Factor = quantity of formula desired/quantity of formula given
= 60/1000
= 0.06
Step 2,
quantity of drug needed = 6g x 0.06 = 0.36

04/09/2024 Pharmaceutical Calculation 116


Cont….
Example 2;
The following is a formula for 100 triple estrogen capsules.
Calculate the quantities of the first three ingredients, in grams, and the two
ingredients, in kg, required to prepare 5000 such capsules.
 Estriol ………………………...200mg
 Estrone ………………………..25mg
 Estradiol ………………………25mg
 Polyethylene Glycol 1450 ….....20g
 Polyethylene Glycol 3350 ….....20g

04/09/2024 Pharmaceutical Calculation 117


Cont……
Soln;
Step 1. factor = quantity of formula desired/quantity of formula given
= 5000/100 = 50
Step 2.
 Estriol ………………………..200mg x 50 = 10g
 Estrone ……………………….25mg x 50 = 1.25g
 Estradiol ………………………25mg x 50 = 1.25g
 Polyethylene Glycol 1450 ……20g x 50 = 1kg
 Polyethylene Glycol 3350 …....20g x 50 = 1kg

04/09/2024 Pharmaceutical Calculation 118


Cont……
Example 3.
The following formula for an ophthalmic ointment is as follows
 Sulfacetamide sodium……..10%w/w
 Prednisolone acetate ……….0.2%w/w
 Phenylmercuric acetate ……0.0008%w/w
 Mineral oil …………………1%w/w
 White petrolatum qs ad ……3.5g
How much of each ingredient would be needed to manufacture 2000 such tubes of
ointment?

04/09/2024 Pharmaceutical Calculation 119


Cont’d…
Step 1.
Factor = quantity of formula desired/quantity of formula given
= 2000/1
= 2000
Step 2.
Total weight of ophthalmic ointment
= 3.5g x 2000
= 7000g
Step 3.
Sulfacetamide sodium …….10%w/w
10g/100g = x/7,000g
x = 700g
Prednisolone acetate ……...0.2%w/w
0.2/100g = x/ 7000g
x = 14g

04/09/2024 Pharmaceutical Calculation 120


Cont……
Phenylmercuric acetate ……
0.0008%w/w
0.0008g/100g = x/7000g
x = 56mg
Mineral oil……………1%w/w
1g/100 = x/7,000g
x = 70g
White petrolatum qs ad……3.5g
=7000g – 700g-14g-0.056g- 70g
= 6215.944g

04/09/2024 Pharmaceutical Calculation 121


Cont….…
Example 4;
Calculate using the following formula for the amounts of ingredients needed to
produce 500g of product:
 Calcium carbonate ……. 5parts
 Sodium bicarbonate …… 5parts
 Bismuth subcarbonate …. 3parts
total parts 13parts
Factor = quantity of formula desired/quantity of formula given
= 500/13 = 38.46

04/09/2024 Pharmaceutical Calculation 122


Cont..…

To calculate quantity of each ingredient


 Calcium carbonate……5parts
= 5 * 38.46
= 192.3 g
Sodium bicarbonate…...5parts
38.46 * 5g = 192.3 g
Bismuth subcarbonate…3parts
= 38.46 * 3g
= 115.4g

04/09/2024 Pharmaceutical Calculation 123


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04/09/2024 Pharmaceutical Calculation 124


DILUTION AND CONCENTRATION

04/09/2024 Pharmaceutical Calculation 125


Learning objective

Upon successful completion of this chapter, the student will be able to;
 Define and know when and how to use dilution and concentration; Triturations;
Alligation medial and Alligation Alternate
 Perform calculations for; altering product strength by dilution, concentration, or
fortification of the preparation and use of stock solutions.
 Apply allegation medial and allegation alternate in problem-solving.

04/09/2024 Pharmaceutical Calculation 126


Introduction to Dilution and Concentration
The concentration of a solution is the amount of solute dissolved in a specific
amount of solvent.

t i on
s ol u
r d
ate tion)
ce n t
Con s o lu
St o ck
(

l ut i on
e d so
Dilut

Concentration = amount of solute


amount of solution
04/09/2024 Pharmaceutical Calculation 127
Cont….…
Dilution is;
 The process of preparing a less concentrated solution from a more concentrated
one.
 The process of decreasing the concentration of a stock solution by adding more
solvent to the solution.
NB.
 A stock solution is a concentrated solution that will be diluted to a lower
concentration for actual use.

04/09/2024 Pharmaceutical Calculation 128


Cont……
 The solvent added is usually the universal solvent, known as water.
 The more solvent you add, the more diluted the solution will get.

04/09/2024 Pharmaceutical Calculation 129


Cont.…
 The strength of a pharmaceutical preparation may be increased or decreased by
changing the proportion of active ingredient to the whole.

04/09/2024 Pharmaceutical Calculation 130


Cont…

A preparation may be strengthened or made more concentrated by;


 The addition of active ingredient,
 Admixture with a like preparation of greater strength,
 Through the evaporation of its vehicle, if liquid.
The strength of a preparation may be decreased or diluted by
 The addition of diluent, or
 Admixture with a like preparation of lesser strength.

04/09/2024 Pharmaceutical Calculation 131


Cont…
The diluent is selected based on its compatibility with the vehicle of the original
product; that can be, aqueous, alcoholic, hydroalcoholic, or other.

Add Solvent

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Cont…
In general,

In a dilution; In concentrated solution;


 Diluent is added. Preparation of greater strength and/or
 volume increases. active ingredient added,
Vehicle evaporated, if liquid
 concentration decreases.
Concentration increased.

04/09/2024 Pharmaceutical Calculation 133


Relationship between strength and total quantity

 If a mixture of a given percentage or ratio strength is diluted to twice its original


quantity, its active ingredient will be contained in twice as many parts of the
whole, and its strength therefore will be reduced by one half.

Diluent

04/09/2024 Pharmaceutical Calculation 134


Cont.…
If, then, 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; that is,
 The percentage or ratio strength decreases as the quantity increases, and conversely.
 This relationship is generally true for all mixtures except solutions containing
components that contract when mixed together.

04/09/2024 Pharmaceutical Calculation 135


Cont.…
Dilution equation:
(1st quantity) x (1st concentration) = (2nd quantity) x (2nd concentration), or
Q1 x C1 = Q2 x C2
The quantity of solute in a solution refers to the total quantity of solute in the
solution.
 It is generally measured by weight (using units such as grams) or by volume
(using units such as milliliters).

04/09/2024 Pharmaceutical Calculation 136


Cont…

Concentration, on the other hand, refers to the amount of solute per unit of
solution.
Concentration can be expressed as a ratio; i.e. g/ml, ml/ml, g/g

Concentration of solution = amount of solute


amount of solution

04/09/2024 Pharmaceutical Calculation 137


Dilution and concentration of liquids
Stock solutions
Are concentrated solutions of active (e.G., Drug) or inactive (e.G., Colorant)
substances and are used by pharmacists as a convenience to prepare solutions
of lesser concentration.
Example;
1, How many milliliters of a 1: 400 w/v stock solution should be used to make 4
liters of a 1 : 2000 w/v?

04/09/2024 Pharmaceutical Calculation 138


Cont’d…

Given; C1 = 1: 400 = 0.25% V1 = y


C2 = 1 : 2000 = 0.05% V2 = 4 liters = 4000 mL
Soln;
V1 x C1 = V2 x C2
0.25%w/v x y mL = 4000 (mL) x 0.05% w/v
y = 800 mL Or,
1⁄400w/v x y mL = 4000 (mL) x 1⁄2000w/v,
y = 800 mL

04/09/2024 Pharmaceutical Calculation 139


Cont……
2, If 500 mL of a 15% v/v solution are diluted to 1500 mL, what will be the
percentage strength (v/v)?
Soln;
Given.
v1 = 500mL c1 = 15%w/v
v2 = 1,500mL c2 =y %w/v
v1 x c1 = v2 x c2
500mL x 15%w/v = 1500mL x y%w/v
y = 5%w/v

04/09/2024 Pharmaceutical Calculation 140


Dilution and concentration of Solids and Semisolid

 The dilution of solids in pharmacy occurs when there is need to achieve a lower
concentration of an active component in a more concentrated preparation (e.g., a
powdered vegetable drug).
 Reducing or enhancing the strengths of creams and ointments is a usual part of a
compounding pharmacist’s practice to meet the special needs of patients.

04/09/2024 Pharmaceutical Calculation 141


E.g. If 30 g of a 1% hydrocortisone ointment were diluted with 12g of Vaseline, what
would be the concentration of hydrocortisone in the mixture?
Soln:
Given;
Hydrocortisone total weight = 30 g x 1%w/w = 0.3 g
Total weight of mixture = 30 g + 12 g = 42 g,

Concentration of hydrocortisone in preparation

= amount of solute / total amount of preparation

= 0.3 g/42 g x 100%


Q 1 x C1 = Q2 x C2
= 0.71%w/w, Or

= 30 x 1%w/w = 42 x y
04/09/2024 Pharmaceutical Calculation 142
y = 0.71%w/w
Cont……
2, How many grams of opium containing 15%w/w of morphine and how many
grams of lactose should be used to prepare 150 g of opium containing 10% w/w of
morphine?
Soln;
Q1 x C1 = Q2 x C2
x g X 15%w/v = 150g X 10%w/v
x = 100 g of opium containing 15%morphine
150 g - 100g = 50 g of lactose

04/09/2024 Pharmaceutical Calculation 143


Triturations
 Trituration is a dilution of a potent drug powder with an inert diluent powder,
usually lactose, in a definite proportion by weight.
 prepared by diluting one part by weight of the drug with nine parts of finely
powdered lactose.
 They are, therefore,10% or1:10 w/w mixtures
 We can then remove a weighable portion (aliquot) of the mixture containing the
desired quantity of substance to maintain an acceptable range of accuracy.

04/09/2024 Pharmaceutical Calculation 144


Cont…
 The trituration is done by dissolving in
 Sterile water
 Sodium chloride for injection, or
 Finely powdered lactose prior to administration .
 Lactose is the most commonly used diluent in solid dosage form pharmaceuticals
such as powders, tablets and capsules;
B/c of its extremely low incidence of side effects, ready availability, and low cost.

04/09/2024 Pharmaceutical Calculation 145


Cont…
Ratio and proportion can be used to determine the weight of drug and lactose
required to make the trituration as well as the weight of the aliquot to be used to
fill the prescription.
Wt of drug in trituration = W t of drug in aliquot
Wt of trituration Wt of aliquot

04/09/2024 Pharmaceutical Calculation 146


Cont…
E.g. How many grams of a 1:10 trituration are required to obtain 25 mg of drug?
Sol/n;
1:10 trituration means, 10 g of trituration contain 1 g of drug
25 mg = 0.025 g
Wt of drug in trituration = W t of drug in aliquot
Wt of trituration Wt of aliquot
1(g) = 0.025 (g)
10 (g) x (g) x = 0.25 g

04/09/2024 Pharmaceutical Calculation 147


 2, How many milliliters of an injection prepared by dissolving 100 mg of a 1:10
trituration of mechlorethamine hydrochloride in sufficient water for injection to
prepare 10 mL of injection, is required to obtain 5 mg of drug?
Soln;
NB.
 1:10 trituration = 1mg of drug in 10ml of solution for injection
100 mg of trituration = 10 mg of drug
10 mg of drug in 10 mL of injection
10 (mg)/5 (mg) = 10 (mL)/x (mL)
x = 5 mL, answer.

04/09/2024 Pharmaceutical Calculation 148


Alligation

Alligation is an arithmetical method of solving problems that involves the mixing


of solutions or mixtures of solids possessing different percentage strengths.( tying
together)
There are two types of alligation methods.
A, Alligation medial.
B, Alligation alternate
A, 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 may be easily
calculated.

04/09/2024 Pharmaceutical Calculation 149


Cont…
E.g.
1) What is the percentage strength (v/v) of alcohol in a mixture of 3000 mL of 40%
v/v alcohol, 1000mL of 60% v/v alcohol, and 1000 mL of 70% v/v alcohol?
 Assume no contraction of volume after mixing.

04/09/2024 Pharmaceutical Calculation 150


Cont…
Soln; Total quantity of alcohol
0.40 x 3000 mL = 1200 mL
0.60 x 1000 mL = 600 mL
0.70 x 1000 mL = 700 mL
Total 5000 mL = 2500 mL
Total volume of solution total volume of alcohol
Alcohol strength = 2500mL x 100%
5000 mL
= 50%v/v

04/09/2024 Pharmaceutical Calculation 151


Cont…
B, Alligation alternate
 It is a method by which we may calculate the number of parts of two or more
components of a given strength when they are to be mixed to prepare a
mixture of desired strength.
Examples;
1. In what proportion should alcohols of 95% and 50% strengths be mixed to make
70% alcohol?

04/09/2024 Pharmaceutical Calculation 152


Cont…
NB.
 The difference between the strength of the stronger component (95%) and the
desired strength (70%) indicates the number of parts of the weaker to be used (25
parts), and
 The difference between the desired strength (70%) and the strength of the weaker
component (50%) indicates the number of parts of the stronger to be used (20
parts).

04/09/2024 Pharmaceutical Calculation 153


Cont…
 The mathematical validity of this relationship can be demonstrated.

 Percent given Proportional parts required

Percent desired

95% mi n
us x

s
70 give
giv
e s

from
50% y
04/09/2024 Pharmaceutical Calculation 154
Cont…

Soln; The result can be shown to be correct by


alligation medial:
= 95 * x + 50 * y = 70(x + y)
or 95 x 4 = 380
= 0.95 * x + 0.5 * y = 0.7(x + y) 50 x 5 = 250
= 0.95x + 0.5y = 0.7x + 0.7y Totals: 9 = 630
= 0.95x – 0.7x = 0.7y – 0.5y
630/9 = 70%
= 0.25x = 0.2y
= x/y = 0.2/0.25
= 4parts/5parts = 4 : 5, answer
04/09/2024 Pharmaceutical Calculation 155
Cont…
2. In what proportion should 20% benzocaine ointment be mixed with an ointment
base to produce a 2.5% benzocaine ointment?
Soln; 20% 2 .5% 2.5 parts of 20% ointment
0% 17.5 parts of ointment base
Relative amounts: 2.5 : 17.5, or 1 : 7, answer
Prove: 20 x 1 = 20
0x 7 = 0
Totals: 8 = 20 20 / 8 = 2.5%

04/09/2024 Pharmaceutical Calculation 156


Specific Gravity of Mixtures
 The methods of alligation medial and alligation alternate may be used in solving
problems involving the 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.

04/09/2024 Pharmaceutical Calculation 157


Examples;
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, and 1000 mL
of an elixir with a specific gravity of 0.950?
Soln;
1.300 x 1000 = 1300
1.250 x 400 = 500
0.950 x 1000 = 950
Totals: 2400 = 2750
2750/2400 = 1.146

04/09/2024 Pharmaceutical Calculation 158


Cont…
2. In what proportion must glycerin with a specific gravity of 1.25 and water be
mixed to prepare a liquid having a specific gravity of 1.10?
Soln;
1.25 1.10 0.10 parts of glycerin
1.00 0.15 parts of water
Relative amounts: 0.10 : 0.15, or 2 : 3, answer.

04/09/2024 Pharmaceutical Calculation 159


Quiz (5%)

1. In what proportion should a preparation of 50% and 20% strengths be mixed to


make 10% strength of the preparation?
2. What is the percentage strength (v/v) of alcohol in a mixture of 3000 mL of
30%v/v alcohol, 1000mL of 50%v/v alcohol, and 1000 mL of 40%v/v alcohol?

04/09/2024 Pharmaceutical Calculation 160


Thank you

04/09/2024 Pharmaceutical Calculation 161


Isotonic, buffer and electrolyte solutions

04/09/2024 Pharmaceutical Calculation 162


Learning objectives

Upon successful completion of this chapter, the student will be able to:
 Differentiate between the terms isotonic, hypertonic, and hypotonic.
 Calculate dissociation constant
 Perform the calculations required to prepare isotonic compounded prescriptions.
 State the buffer equation and apply it in calculations.

04/09/2024 Pharmaceutical Calculation 163


Introduction
Solution – is a mixture of one or more solutes dissolved in a solvent.
 There are different types medications that can be used as solution types of dosage
form.
 They can be used for parentral, opthalmic, nasal, rectal and otic routes of
administration.
 After application usually there is a higher concentration of solutes on one side of
the membrane than the other.

04/09/2024 Pharmaceutical Calculation 164


Cont…
 If the total concentration of all dissolved solutes is not equal on both sides, there
will be net movement of water(solvent) molecules into or out of the cell.
 This flow can be by diffusion or osmosis.
 A. Diffusion is the movement of particles from an region of higher concentration
to one of lower concentration

04/09/2024 Pharmaceutical Calculation 165


Cont…
B. Osmosis is the flow of a solvent from a dilute solution into a more concentrated
solution, through a semipermiable membrane.
 Then the concentrations become equalized.

Osmotic pressure: -
 The pressure of a solution against a semipermeable membrane to prevent
water from flowing inward across the membrane.
 Pressure responsible for osmosis(that stops the process of osmosis)

04/09/2024 Pharmaceutical Calculation 166


Cont’d…
Tonicity: -
A measure of the amount of substance dissolved in a liquid (in most cases
water)
A measure of the effective osmotic pressure gradient of two solutions
separated by a semi permeable membrane.

04/09/2024 Pharmaceutical Calculation 167


Cont…
 There are three classifications of tonicity that one solution can have relative to
another. The three are;
Hypertonic,
Hypotonic, and
Isotonic
 Whether there is net movement of water into or out of the cell and which direction
it moves depends on whether the cell’s environment is isotonic, hypotonic, or
hypertonic

04/09/2024 Pharmaceutical Calculation 168


Cont…
A hypotonic solution:,
 Solution that have a lower concentration of solutes than the cell.
 Solutions that have lower osmotic pressure than that of a body fluid.
 The cell will also have a higher osmotic pressure (the tendency for water to move into
a cell by osmosis than the solution surrounding it).
 This will cause fluid to move into the cell.

04/09/2024 Pharmaceutical Calculation 169


Cont.…
Hypertonic solution:-
 Solution that have a higher concentration of solutes than the cell and will have a
higher osmotic pressure outside the cell than inside the cell.
 It is a solution of higher osmotic pressure than that of body fluids.
Isotonic solution: -
 Solution having the same osmotic pressure as a specific body fluid.

04/09/2024 Pharmaceutical Calculation 170


Animal and plant cells within solution of different tonicity

04/09/2024 Pharmaceutical Calculation 171


Cont…

Many solutions intended to be mixed with body fluids, such as ophthalmic and
parenteral administration, are designed to have the same osmotic pressure for
greater patient comfort, efficacy, and safety
 i.e. minimize tissue irritation, pain and cell fluid imbalance
So, solution to be mixed with body fluids should have the same osmotic pressure
with body fluids.

04/09/2024 Pharmaceutical Calculation 172


Physical/chemical considerations in the
preparation of isotonic solutions
The calculations involved in preparing isotonic solutions may be made in terms of
data relating to the colligative properties of solutions.
Colligative properties of solutions
 From Greek word" collected together”,
 Properties that depend upon the concentration of solute molecules or ions, but
not upon the identity of the solute.

04/09/2024 Pharmaceutical Calculation 173


Cont…
It includes;
 freezing point depression,
 boiling point elevation,
 vapor pressure lowering, and osmotic pressure.
Theoretically, any one of these properties may be used as a basis for determining
tonicity.

04/09/2024 Pharmaceutical Calculation 174


Cont…
Osmotic pressure is one of colligative properties of solutions that may be used as
a basis for determining tonicity in isotonic solution preparation.
It depends on the nature of the solute.
 If the solute is a nonelectrolyte, its solution contains only molecules and the osmotic
pressure varies with the concentration of the solute.
 If the solute is an electrolyte, its solution contains ions and the osmotic pressure
varies with both the concentration of the solute and its degree of dissociation.

04/09/2024 Pharmaceutical Calculation 175


Cont…

Thus, solutes that dissociate present a greater number of particles in solution and
exert a greater osmotic pressure than undissociated molecules.
Methods for adjusting isotonicity
I. Freezing point depression (lowering) method
II. Sodium chloride equivalent method

04/09/2024 Pharmaceutical Calculation 176


Freezing point determining tonicity in isotonic solution
preparation

 Practically and most conveniently, a comparison of freezing points is used for


determining tonicity.
 It is generally accepted that -0.52 oC is the freezing point of both blood serum and
lacrimal fluid.
 It is assumed that any aqueous solution freezing at -0.52 oC is isotonic with blood.
 It is rare that a simple aqueous solution of the therapeutic agent to be injected into
body fluid has a freezing point of -0.52 oC

04/09/2024 Pharmaceutical Calculation 177


Cont…
 To obtain this freezing point
 Add some other therapeutically inactive solute if the solution is hypotonic (freezing
point above -0.52 oc) or
 Dilute the solution if it is hypertonic (freezing point below -0.52 oc).
 The usual practice is to add either sodium chloride or dextrose to adjust hypotonic
solutions to isotonic.

04/09/2024 Pharmaceutical Calculation 178


Cont..
• If the concentration and the corresponding freezing point dep. of a solution are
known, the concentration of the isotonic solution with a specific body fluid can be
calculated using the following relationship

04/09/2024 Pharmaceutical Calculation 179


Examples
I. How many milligrams each of sodium chloride and dibucaine hydrochloride are
required to prepare 30 ml of a 1% solution of dibucaine hydrochloride isotonic
with tears?(fpNacl=0.58 fpdibucaine=0.08) by proportion:

note = =0.52-0.08=0.44
x= 0.76% (the concentration of sodium chloride needed to lower the freezing point
by 0.44,required to make the solution isotonic)
30 g*0.76=228 mg sodium chloride.

04/09/2024 Pharmaceutical Calculation 180


Sodium chloride equivalent method

 A sodium chloride equivalent, E value, is defined as the weight of sodium chloride


that will produce the same osmotic effect as 1 g of the drug.
 Can be obtained from tables in pharmaceutical calculations texts.
 It can be also calculated using the following formula

04/09/2024 Pharmaceutical Calculation 181


Cont..
 NB: i is dissociation value (ionization value);
 MW is molecular weight
 The i value for substances can be estimated:
 Non electrolytes and substances of slight dissociation: 1.0
 Substances that dissociate into 2 ions: 1.8
 Substances that dissociate into 3 ions: 2.6
 Substances that dissociate into 4 ions: 3.4
 Substances that dissociate into 5 ions: 4.2

04/09/2024 Pharmaceutical Calculation 182


Examples
 Calculate the sodium chloride equivalent for timolol maleate, which dissociates
into two ions and has a molecular weight of 432.
Timolol maleate, i factor 1.8
58.5/1.8 =1.8/432
=0.14, answer

04/09/2024 Pharmaceutical Calculation 183


Cont..
 The calculation of isotonic solutions with sodium chloride equivalent may be
outlined as follows:
Step 1. Calculate the amount (in grams) of sodium chloride represented by the
ingredients in the prescription
Multiply the amount (in grams) of each substance by its sodium chloride equivalent
Step 2. Calculate the amounts of sodium chloride, alone, that would be contained in
an isotonic solution of the volume specified in the prescription, namely, the
amount of NaCl in a 0.9% solution of the specified volume

04/09/2024 Pharmaceutical Calculation 184


Cont..
Step 3. Subtract the amount of sodium chloride represented by the ingredients in
the prescription (step 1) from the amount of sodium chloride, alone, that would be
represented in the specific volume of an isotonic solution (Step 2)
The answer represents the amount (in grams) of sodium chloride to be added to make
the solution isotonicTI
Step 4. If an agent other than sodium chloride, such as boric acid, dextrose, or
potassium nitrate, is to be used to make a solution isotonic, divide the amount of
sodium chloride (Step 3) by the sodium chloride equivalent of the other substance

04/09/2024 Pharmaceutical Calculation 185


Examples
1.How many grams of sodium chloride should be used in compounding the
following prescription
Rx
 Pilocarpine nitrate 0.3 g
 Sodium chloride q.s.
 Purified Water ad 30 mL
 Make isoton. Sol.
 Sig. for the eye
Sod. Chloride equivalent for Pilocarpine nitrate = 0.23

04/09/2024 Pharmaceutical Calculation 186


Cont…
Soln;
 The procedure for the calculation of isotonic solutions with sodium chloride
equivalents
Step. 1. The amount (in grams) of sodium chloride represented by the ingredients in
prescription
= 0.23 X 0.3g of pilocarpine nitrate
= 0.069 g of NaCl represented by the pilocarpine nitrate

04/09/2024 Pharmaceutical Calculation 187


Cont..…
Step. 2- The amount (in grams) of sodium chloride, alone, that would be contained
in an isotonic solution of the volume specified in the prescription
30 × 0.009 = 0.270 g of sodium chloride in 30 ml of an isotonic sodium chloride
solution
Step. 3; the amount (in grams) of sodium chloride to be added to make the solution
isotonic.
= 0.27 - 0.069 = 0.201 g of NaCl should be used.

04/09/2024 Pharmaceutical Calculation 188


Cont…

Phenacaine Hydrochloride…….1%, (E 0.20)


 Rx Chlorobutanol……………………….. ½%,(E 0.24)
 Boric Acid……………………………… q.s.,(E 0.52)
 Purified Water ad ….......……..60, (E 0.009)
 Make isotonic. sol.
 Sig. One drop in each eye.
• Prescription calls for 0.6 g of phenacaine hydrochloride and 0.3 g of
chlorobutanol.

04/09/2024 Pharmaceutical Calculation 189


Cont…

Step 1)
 0.20 × 0.6g = 0.120g of NaCl represented by phenacaine hydrochloride
 0.24 × 0.3g = 0.072g of NaCl represented by chlorobutanol
 Total: 0.192 g of NaCl chloride represented by both ingredients
Step 2)
 60×0.009 = 0.540 g of NaCl in 60 ml of an isotonic NaCl solution

04/09/2024 Pharmaceutical Calculation 190


Cont..

Step 3)
0.540 g (from Step 2)-0.192 g (from Step 1)
=0.348 g of NaCl required to make the solution isotonic .
But because the prescription calls for boric acid:
Step 4)
0.348 g/0.52 (NaCl equivalent of boric acid)
= 0.669 g of boric acid to be used.

04/09/2024 Pharmaceutical Calculation 191


Buffer and buffer solution

04/09/2024 Pharmaceutical Calculation 192


Introduction
 pH is a measure of the concentration of H+ [H3O+] ions in a solution.
 Only the concentration of H+ and OH- molecules determine the pH.
 When the concentration of H+ and OH- ions are equal, the solution is said to be
neutral.
 If there are more H + than OH- molecules the solution is acidic, and if there are
more OH- than H + molecules, the solution is basic.

04/09/2024 Pharmaceutical Calculation 193


Cont…
 Substances or combinations of substances in aqueous solution that imparts to the
system the ability to maintain a desired pH at a relatively constant level are called
buffers.
 The ability to resist changes in pH is referred to as buffer action.
 A buffer solution is a solution that resists changes in pH caused by the addition of
small amounts of a strong acid or alkali.

04/09/2024 Pharmaceutical Calculation 194


Cont…

 A buffer solution is usually composed of


 a weak acid and a salt of the acid
 Eg. acetic acid and sodium acetate, or
 a weak base and a salt of the base
 Eg. ammonium hydroxide and ammonium chloride.

04/09/2024 Pharmaceutical Calculation 195


There are two types of buffers:
1. Acidic
2. Basic
1. Acidic buffers comprise of a weak acid and its salt.
e.g. ethanoic acid and sodium ethanoate.
2. Basic Buffers comprise of a weak base and its conjugate salt.
e.g. aqueous ammonia and ammonium chloride.

04/09/2024 Pharmaceutical Calculation 196


Advantages of buffer

 The most common buffer systems are used in


I. the preparation of such dosage forms as injections and ophthalmic solutions,
which are placed directly into pH-sensitive body fluids;
II. the manufacture of formulations in which the pH must be maintained at a
relatively constant level to ensure maximum product stability; and
III. pharmaceutical tests and assays requiring adjustment to or maintenance of a
specific pH for analytic purposes.

04/09/2024 Pharmaceutical Calculation 197


Cont…

Typical buffer systems that may be used in pharmaceutical formulations include


the following pairs:
 Acetic acid and sodium acetate,
 Boric acid and sodium borate, and
 Disodium phosphate and sodium acid phosphate.

04/09/2024 Pharmaceutical Calculation 198


pH in the Absence of a Buffer
If a strong acid or strong base is added to water, the pH will change dramatically.
HCl + H2O → H3O + + Cl -
The resulting large concentration of (H +) makes the solution more acidic and
leads to a dramatic drop in the pH.

04/09/2024 Pharmaceutical Calculation 199


NaOH + H2O → OH-+ Na+

 The resulting large concentration of OH- makes the solution more basic and
leads to a dramatic increase in the pH.
 As the concentration of OH- ions goes up, the concentration of H + ions goes
down.)
04/09/2024 Pharmaceutical Calculation 200
Change in pH with Addition of an Acid or Base

Buffer equation(Henderson-Hasselbalch equation)


Dissociation constant (Kd) (ionization constant)
A specific type of equilibrium constant that measures the propensity of a larger
object to separate (dissociate) reversibly into smaller components, as when a
complex falls apart into its component molecules, or when a salt splits up into its
component ions.

04/09/2024 Pharmaceutical Calculation 201


Cont…
For the acid dissociation reaction
HA H+ + A-
Ka = [H+][A-]
[HA]
For the base dissociation reaction
BOH OH- + B +
Kb = [OH-][B+]
[BOH]
NB:
B+ = salt
BOH = base
04/09/2024 Pharmaceutical Calculation 202
Cont…
Not only acids and bases dissociate, water dissociates too: and the equilibrium of
this reaction is described by the equation.
H2O-------- H+ + OH-
K = [H+][OH-]
H2O
Water ionization constant or water ion product:
Kw = [H+][OH-]
PKw = PH + POH

04/09/2024 Pharmaceutical Calculation 203


The Henderson-Hasselbalch equation is used mostly to calculate pH of solutions
created mixing known amounts of acids and conjugate bases (or neutralizing part
of acid with a strong base).
pKa = -log Ka

Ka = [H+][A-]
[HA]
pKa = -log (H+) – log[salt/acid]
pH = pKa + log[salt/acid]

Kb = [OH-][B+]
[BOH]
pOH = pKb + log[B+/BOH]
04/09/2024 Pharmaceutical Calculation 204
Cont…
E.g. 1, What is the pH of a buffer solution prepared with 0.05 M sodium borate and
0.005 M boric acid?
The pKa value of boric acid is 9.24 at 25C.
Soln;
pH = pKa + log[salt/acid]

= 9.24 + log[0.05/0.005]
= 9.24 + log10
= 9.24+1
= 10.24, answer.
04/09/2024 Pharmaceutical Calculation 205
Cont…
E.g. 2, Calculate the pH of a buffer solution made from 0.20 M HC 2H3O2 and 0.50 M
C2H3O2- that has an acid dissociation constant for HC2H3O2 of 1.8 x 10-5.

Soln;
pH = pKa + log[salt/acid]

= pKa + log ([C2H3O2-] / [HC2H3O2])

= -log (1.8 x 10-5) + log (0.50 M / 0.20 M)


= -log (1.8 x 10-5) + log (2.5)
= 4.7 + 0.40
= 5.1
04/09/2024 Pharmaceutical Calculation 206
Cont..…

E.g. 3, Calculate the change in pH after adding 0.04 mol of sodium hydroxide to a
liter of a buffer solution containing 0.2 M concentrations of sodium acetate and
acetic acid. The pKa value of acetic acid is 4.76 at 25C.
Soln;
The pH of the buffer solution is calculated by using the buffer equation as follows:
pH = pKa + log[salt/acid]
= 4.76 + log[0.2/0.2]
= 4.76 + log 1
= 4.76

04/09/2024 Pharmaceutical Calculation 207


Cont…
The addition of 0.04 mol of sodium hydroxide
 Converts 0.04mol of acetic acid to 0.04mol of sodium acetate; and
 The concentration of acetic acid is decreased and
 The concentration of sodium acetate is increased by equal amounts
pH = pKa + log[(salt + base)/(acid – base)]
= pKa + log[(0.2 + 0.04)/(0.2 - 0.04)]
= pKa + log[0.24/0.16]
= 4.76 + 0.1761
= 4.9361 or 4.94

04/09/2024 Pharmaceutical Calculation 208


Quiz-2(5%)

1. How many grams of sodium chloride should be used in compounding the


following prescription?
 Chloramphenicol 0.5g
 Sodium Chloride q.s.
 Purified Water ad 50mL
 Make isoton. sol.
 Sig. Eye drops.
Sodium chloride equivalent of Chloramphenicol=0.10

04/09/2024 Pharmaceutical Calculation 209


Thank you

04/09/2024 Pharmaceutical Calculation 210


Calculations involving parenteral admixtures

04/09/2024 Pharmaceutical Calculation 211


Objectives
Upon successful completion of this chapter, the student will be able to:
 Perform calculations for dry powder for reconstitution.
 Perform calculations for intravenous additives.
 Perform rate-of-flow calculations for intravenous fluids.

04/09/2024 Pharmaceutical Calculation 212


Introduction

 Parenteral is any medication route other than the alimentary canal and thus,
includes all routes of injection.
 Injections are sterile pharmaceutical solutions or suspensions of a drug
substance in an aqueous or nonaqueous vehicle.
 They are administered by needle into almost any part of the body, including;
 The joints (intra-articular), joint fluid (intrasynovial),
 Spinal column (intraspinal), spinal fluid (intrathecal),
 Arteries (intra-arterial), and the heart (intracardiac).

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Cont…

However, most injections are administered into


 A vein (intravenous, I.V., Iv),

 Muscle (intramuscular, I.M., Im),

 Skin (intradermal, i.D., ID, intracutaneous), or

 Under the skin (subcutaneous, sub-Q, SQ, hypodermic).

04/09/2024 Pharmaceutical Calculation 214


Cont…
Depending upon their use, injections are packaged
 in small volumes in ampoules or
 in prefilled disposable syringes for single-dose use;

In large volume plastic bags or glass containers for administration by slow
intravenous infusion.

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Cont…
 In vials and pen-injectors for single- or multiple-dose use

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Cont…
Some injections are available as;
 Prepared solutions or suspensions with their drug content labeled as, for example,
‘‘10 mg/ml.’’ Or
 Others contain dry powder for reconstitution to form a solution or suspension by
adding a specified volume of diluent prior to use and are labeled as, for example, ‘‘10
mg/vial.’’

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Dry powders for reconstitution

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Cont…

 They are provided as dry powder form for reconstitution with purified water or
special diluent at the time a prescription or medication order is received.
 It is to enhance the shelf-life of these drugs that lose their potency in a relatively
short period when prepared in a liquid dosage form i.e. suspension or emulsion.
 In addition to therapeutic agents, the powder contains such pharmaceutical
ingredients as solubilizing or suspending agents, stabilizers, colorants, sweeteners,
and flavorants.
 The final volume of product is the sum of the volume of solvent or diluent added
and the volume occupied by the dissolved or suspended powder mixture.

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Calculations for the Constitution of Dry Powders for Oral Use

E.g.1. The label for a dry powder package of cefprozil for oral suspension directs
the pharmacist to add 72mL of purified water to prepare 100mL of suspension. If
the package contains 2.5g of cefprozil, how many milligrams of the drug would
be contained in each teaspoonful dose of the constituted suspension?
Soln;
2.5g (2500mg) = 100ml
X = 5ml(1tspf)
2500mg/100mL = x/5mL
x = 125mg of cefprozil

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Cont…
2. Label instructions for an ampicillin product call for the addition of 78mL of water
to make 100mL of constituted suspension such that each 5mL contains 125 mg of
ampicillin. Calculate the volume represented by the suspended powder in the
product and the total content of ampicillin.
A. Volume of powder:100mL − 78mL = 22mL
B. Each 5mL contains 125mg of ampicillin, the total amount of ampicillin in the
100mL product is:
125mg/5mL = x/100mL, x = 2500mg ampicillin.

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Calculations for the Constitution of Dry Powders for Parenteral
Use

E.g.1 Label instructions for the reconstitution of a 500mg vial of ceftazidime for
intramuscular injection call for the addition of 1.5mL of diluent to prepare 1.8mL
of injection. Calculate;
A. The volume occupied by the dry drug,
B. The concentration of ceftazidime in the injection, in mg/ml,
C. The volume of injection to provide a dose of 250 mg of ceftazidime.

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Cont…
Soln
a. volume of ceftazidime = total solution volume – water volume
= 1.8mL − 1.5mL = 0.3mL
b. (ceftazidime) in mg/mL
=500 mg/1.8mL
= 277.8 mg/mL, and
c. 500mg/1.8mL = 250mg/xmL
= 250 mg × 1.8mL/500 mg
= 0.9mL

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Intravenous Admixtures

 An IV admixture is the preparation of a pharmaceutical mixture of two or more


drugs into a large volume of sterile IV fluid.
 IV fluid includes;
 Sodium chloride injection,
 Dextrose injection,
 Lactated ringer’s injection, and others.

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Cont…

E.g. How many grams each of dextrose and sodium chloride are used to prepare a
250-mL bag of D5½NS for intravenous infusion?
NB.
D5½NS = 5% Dextrose in 0.45% Sodium Chloride
Answer;
250 mL x 0.05 (5% w/v) = 12.5 g dextrose, and
250 mL x 0.0045 (0.45% w/v) = 1.125 g sodium chloride.

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Hyperalimentation (Total Parenteral Nutrition)

 Parenteral nutrition (PN) or intravenous hyperalimentation (IVH) is


 The feeding of a patient by the intravenous infusion of fluids and basic nutrients.
 Intravenous feeding, especially to individuals unable to take in food through the
alimentary tract.
 PN can be partial or total parenteral nutrition.

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Cont…
 Parenteral nutrition consists of;
A. Macronutrients:
 Carbohydrate (e.g., dextrose)
 Protein (e.g., amino acids)
 Fat (e.g., lipid emulsions)
B. Micronutrients:
 Electrolytes
 Vitamins
 Trace elements
C. Sterile water for injection
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Cont…

E.g. A hyperalimentation order for a patient includes 30mg of amphotericin B,


50units of heparin, 25mEq of potassium acetate, and 1.5mg of folic acid to be
administered intravenously in 1000mLof D5W over an 8hour period. In filling
the medication order, the following sources are available:
 Avail containing 50mg of amphotericin B in 10ml
 A syringe containing 10 units of heparin per ml
 A 20ml vial of 40meq of potassium acetate
 An ampoule containing 5mg of folic acid per ml

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Cont…
 How many mL of each additive should be used in filling the medication order?
Soln;
 Amphotericin B: 50mg/10ml = 30mg/x = 6mL
 Heparin: 10units/1ml = 50units/xmL = 5mL
 Potassium acetate: 40mEq/20mL =25mEq/xmL = 12.5mL
 Folic acid: 5mg/1mL = 1.5mg/xmL = 0.3mL

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Rate of Flow of IV Fluids

On medication orders, the physician specifies the rate of flow of intravenous
fluids in
 Milliliters per minute,
 Drops per minute,
 Amount of drug (as milligrams per hour), or,
 More frequently, as the approximate duration of time of administration of the total
volume of the infusion.

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Cont..

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Cont…
Examples of Rate-of-Flow Calculations
E.g. 1, A medication order calls for 1000 mL of D5W to be administered over an 8-
hour period. Using an IV administration set that delivers 10 drops/mL, how many
drops per minute should be delivered to the patient?

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Cont…
Answer,
Volume of fluid = 1000 mL = 10drops/ml x 1000ml = 10,000gtt
8 hours = 480 minutes
1000 (mL)/480 (minutes) = 2.08 mL per minute
Or,
 Rate of flow (drops/minute) =[Volume infused (mL) x Dripset
(drops/mL)]/Time(’)
= [1000 mL x 10 drops/mL]/480 minutes
= 20.8 or 21 drops per minute

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Cont…
E.g. 2,
 Ten milliliters of 10% calcium gluconate injection and 10 mL of multivitamin
infusion are mixed with 500 mL of a 5% dextrose injection. The infusion is to be
administered over 5hr.
 If the dropper in the venoclysis set calibrates 15 drops/mL, at what rate, in drops
per minute, should the flow be adjusted to administer the infusion over the
desired time interval?

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Cont…

Answer,
Total volume of infusion (mL)= 10 mL + 10 mL + 500 ml =
=520 mL
Total volume of infusion(drops) = 520mL X 15 drops/mL
= 7800 drops
=7800 drops/5hr
26 drops per minute

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Cont…
E.g. 3 An order for a patient, with a 3-liter daily IV fluid limit, calls for 3 L of
D5W with a 100-mL IVPB antibiotic to be run-in alone over a 1-hour period and
administered every 6 hours. The administration set is calibrated to deliver 10
drops per milliliter. Calculate:
a. The flow rate of the IVPB antibiotic;
b. The total flow time for the IV antibiotic /day;
c. The total volume for the IV antibiotic /day;
d. The total flow time for the D5W;
e. The total volume for the D5W;
f. The flow rate for the D5W.

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Cont…
Soln;
(a) [100 mL * 10 drops/mL]/60 min
= 16.6 or 17 drops per minute;
(b) 1 hour * 4 times a day = 4 hours or 240 minutes;
(c) 100 mL 4 times a day = 400 mL;
(d) 24 hours - 4 hours (run time for the antibiotic) = 20 hours or 1200 minutes;
(e) 3000 mL - 400 mL (the IVPB antibiotic) = 2600 mL;
(f) [2600 mL * 10 drops/mL]/1200 min
= 21.6 or 22 drops per minute

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Quiz-3(5%)

1. A patient received 150 mL of an infusion at a rate of 25 mL/hr.


a) What was the infusion time in hours, minutes?

b) If the infusion was begun at 8 AM, at what time was it completed?

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Thank you

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Calculations involving radiopharmaceuticals

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Introduction
 Isotopes can be classified as stable and unstable.
 Stable isotopes never change unless affected
 unstable isotopes are distinguishable by radioactive transformations and
 Hence are said to be radioactive.
 The radioactive isotopes of the elements are called radioisotopes or
radionuclides.
 Nuclear medicine: utilizes radioisotopes and radiation in the diagnosis and
treatment of disease
 Nuclear pharmacy: prepare radioactive pharmaceuticals or
radiopharmaceuticals for use in patient care practice

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Cont…
 Appropriate calculations, dilutions, and corrections for radioactive decay are
performed by nuclear pharmacists when preparing products for dosage
administration.
 An unstable isotope undergoes changes until a stable state is reached, and in the
transformation, it emits energy in the form of radiation.
 Consist of alpha particles, beta particles & gamma rays
 Half-life of the radioisotope: definite time is required for half the original atoms
to decay.
 The rate of decay-dn/dt=λn

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 Follows exponential decay law, N =N0e-λt

 λ is the decay constant


 t time
 N is number of undecomposed atoms
 The half-life (t1/2) = 0.693/λ

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Units of radioactivity:
 Absolute units, total number of atoms disintegrating per unit time.
 The basic unit is the curie (ci), that quantity of a radioisotop in which 3.7 X 10 10
(37 billion) atoms disintegrate per second.
 Also, millicurie (mci) 10-3 ci, microcurie (mci) 10-6 ci, and nanocurie or
millimicrocurie (nci) 10-9 ci
 The international system (SI) unit for radioactivity is the becquerel (bq), defined
as 1 disintegration per second.
 Also, kilobecquerel (kbq) 103 bq, megabecquerel (mbq) 106 bq, and gigabecquerel
(GBq) 109 Bq
1 Ci = 3.7 X 1010 Bq = 3.7 X 104 MBq
1 Bq = 2.7 X 10-11 Ci
1 MBq = 2.7 X 10-5 Ci = 2.7 X 10-2 mCi = 0.027 mCi = 27 mCi
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Cont…

Example:
1. A thallous chloride Tl 201 injection has a labeled activity of 550 microcurie
(mCi). Express this activity in terms of megabecquerels.
550 mCi = 0.55 mCi
1 mCi 37 MBq
0.55 mCi X MBq
X = 20.35
2. The disintegration constant of a radioisotope is 0.02496/day. Calculate the half-
life of the radioisotope.

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Example:
 A vial of sodium phosphate P 32 solution has a labeled activity of 500 Ci (18.5
MBq)/mL.
 How many milliliters of this solution should be administered exactly 10 days after
the original assay to provide an activity of 250 Ci (9.25 MBq)? The half-life of 32P
is 14.3 days.
 The activity exactly 10 days after the original assay is given by
 log N = log 500 - log 2 (0.6993)= 2.6990 - 0.2105
 log N =2.4885
 N =308 µCi/mL, activity after radioactive decay
250µCi =0.81mL

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04/09/2024 Pharmaceutical Calculation 247

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