General Guidance

X Do not rely solely on power point slides.

• Power point slides provide a summary.
√ Make your own notes from other sources e.g. books, internet, etc
 Practice by problem solving.

• Almost certainly the grade you receive will be a reflection of your ability to solve
problems.
• Most Chemistry books will have a section with self-test questions at the end. Practice
them.
• Many of the problems you will be asked to solve require you to proceed through a
series of logical steps to the correct answer.
• Do NOT memorize every concept rather understand them.
• Practice to write down the chemical structures.
• Write your own notes.
• ALMOST CERTAINLY IF YOU MISS MY CLASSES YOU WONT UNDERSTAND MY
NOTES. PK 15 AUGUST2022

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 Reminder
• Last semester you mostly covered how reactions occur.
• You covered some of the experiments you can conduct
to create the drug of your interest.
• Some of those start materials or products could be
inorganic in nature. Irrespective of what you have you
need to analyse it.
• You also need to understand the mechanism that govern
the stability of the product you make.
• This is the essence of this semester.

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 Titrimetric
• One of the analysis methods is Titrimetry.
• In titrimetry you titrate (mix) two solutions together until
an end point is reached. It also means you need to have
means of detecting an end point.

• There area few indicators. For acid base Methyl Orange

(MO) or phenolphthalein (PP) are common

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 eg
The end point in a titration of a 50.00-mL sample of
aqueous HCl was reached by addition of 35.23 mL of 0.250
M NaOH titrant. The titration reaction is:
HCl(aq) + NaOH(aq) ⟶ NaCl(aq) + H2 O(l)
What is the molarity of the HCl?

The end point is when the number of moles in known is

equal to the number of moles in the unknown. So should be
able to calculate and get the volume or concentration of the
unknown.

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 Self test 3.2 page 62
• Some times, one of the solutions has multiple
end points. An example is Na2CO3 which can
react to produce NaHCO3 or H2O and CO2
depending on how much acid is added.
 Self test 3.2 page 62
A sample containing 25.14g of neutral salts,
glucose and sodium carbonate / bicarbonate buffer
was dissolved in 100ml of water.
A 25ml aliquot of the resultant solution required
20.35ml of 0.0987M HCl titrated to the PP end-
point.
Another 25ml aliquot required 56.75ml of the acid
to the MO end-point.
Calculate the percentage of Na2CO3 and NaHCO3
 Gravimetric
• Another analytical test is gravimetry. Gravimetry means we are
dealing with mass (weight).
• Consider the question below

• A 0.4550-g solid mixture containing CaSO4 is dissolved in water and

treated with an excess of Ba(NO3)2, resulting in the precipitation of
0.6168 g of BaSO4. CaSO4 (aq) + Ba(NO3 )2 (aq) ⟶ BaSO4 (s) +
Ca(NO3)2 (aq)
What is the concentration (percent) of CaSO4 in the mixture?

Hint: By adding excess Ba(NO3)2, it means all the sulphate has

reacted. Thus the number of mols of barium sulphate will be equal to
the number of moles of calcium sulphate.
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 Combustion
• You can also use combustion to analyse the content of your
product.
• Consider the example below

• Polyethylene is a hydrocarbon polymer used to produce food-

storage bags and many other flexible plastic items. A combustion
analysis of a 0.00126-g sample of polyethylene yields 0.00394 g of
CO2 and 0.00161 g of H2O. What is the empirical formula of
polyethylene? Solution The primary assumption in this exercise is
that all the carbon in the sample combusted is converted to carbon
dioxide, and all the hydrogen in the sample is converted to water:
Cx Hy(s) + excess O2 (g) ⟶ xCO2 (g) + yH2 O(g)

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 agentimetric
• Sometimes your product may contain silver. In that case
agentimetric methods are more suited for analysis. Consider the
question below.

• What is the concentration of NaCl in a solution if titration of 15.00

mL of the solution with 0.2503 M AgNO3 requires 20.22 mL of the
AgNO3 solution to reach the end point? AgNO3 (aq) + NaCl(aq) ⟶
AgCl(s) + NaNO3 (aq)

• When Ag reacts with Cl, you form AgCl which is sparingly soluble.

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 PHARMACEUTICAL
CHEMISTRY– PHA 201

Lecture 1 Semester 2: Introduction (Outline),

Review of Concentration terms, Introduction to
Titrimetry, Titration curves

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 COURSE OUTLINE
Topics of study

Physical Chemistry
Electrochemistry
Inorganic Chemistry

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 PHYSICAL CHEMISTRY
• 1. Reaction Kinetics
• 2. Thermodynamics
– First and second law of thermodynamics
– Thermochemistry
– Free energy functions and applications
Literature: - Peter Aktins,
- Any book: Introduction to Physical
Chemistry .

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 ELECTROCHEMISTRY

• Conductivity and its measurement

• Conductometric titrations
• Electrochemical cells
• Determination of pH and redox potentials
• Acid/base and redox titrations

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 INORGANIC CHEMISTRY
1. Titrimetric and quantitative analysis
2. Limit tests
3.Pharmaceutical Analysis

Textbook: Watson DG. Pharmaceutical analysis:

a textbook for pharmacy students and
pharmaceutical chemists. 2nd ed. London:
Elsevier Health Sciences; 2005.

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 CONCENTRATION
• Methods of expressing concentration of a solution.
• N.B. Solutions can be solids as well
• Molarity (M)
• Molality (m)
• Normality (N)
• Mole fraction
• Percent of solute
– %w/w
– %v/v
– %w/v
• Parts per million (ppm)
K.K.Nyirenda 15
 INTRODUCTION TO TITRIMETIC
METHODS
• Titration: technique used to determine the
unknown concentration of a substance in
solution by allowing it to react with a
solution containing substance of known
concentration.
• Titrimetric methods are widely used in
pharmaceutical analysis.
• Classical method of analysis (cf
instrumental methods)
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 Titrimetric methods
How do you find the
concentration of an
unknown sample?

One of the ways is

titration with a known
sample

What is titration?

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 ADVANTAGES
• Robustness– stability of solutions
• Sometimes higher precision & accuracy
than instrumental methods
• Direct methods and do not rely on
calibration of instruments
• Cheap
• Some can be automated

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 DISADVANTAGES

• Lack specificity

• Time consuming

• Large amount of sample & reagents

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 REQUIREMENTS
• Reliable glassware
• The analyte
• Chemical of known conc. – standard
solution (Primary stds)
• Accurate determination of completion of
reaction

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 PRIMARY STANDARDS
• Stable chemicals available in high purity

• 1° stds used to standardize other solutions

– become secondary standards e.g.
NaOH, HCl

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 COMMON 1° STDS
• Potassium hydrogen phthalate

• Potassium iodate

• Anhydrous sodium carbonate

• Zinc metal.

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 TYPES OF TITRATIONS
• Acid-base
• Argentimetric
• Compleximetric
• Redox
• Ion Pair
• Potentiometric
• Karl-Fisher
• Automation (FIA)
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• Example 4.14
• Titration Analysis
• The end point in a titration of a 50.00-mL sample of aqueous HCl was
reached by addition of 35.23 mL of 0.250 M NaOH titrant. The titration
reaction is:
HCl(aq) + NaOH(aq) ⟶ NaCl(aq) + H2 O(l)
What is the molarity of the HCl?
Reaction is 1:1
Number of moles of NaoH = 35,23ml X 0.250mol/1000ml =8,81x10 -3 mol
= mols of HCl
Hence concentration of HCl = 1000ml X 8.81x10 -3 mols/50 ml
= 0.176 M

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 ACID-BASE TITRATIONS
• Direct acid-base titrations in aqueous phase
– Strong acid / strong base
– Weak acid / strong base and weak base /
strong acid
• Titrations of salts of weak bases in mixed
aqueous / non-aqueous media
• Indirect titrations in the aqueous phase
• Non-aqueous titrations

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 Endpoint and equivalence point
• Endpoint: the point when the indicator
colour changes (usually the end of the
titration)
• Equivalence point: The point when the
number of equivalents mixed together are
the same
• At equivalent point in acid-base titrations,
[H3O+] = [-OH]

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08/18/2023 K.K. Nyirenda 27
 ENDPOINT DETECTION

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 𝜕 𝑝𝐻
𝜕𝑣

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 TITRATION CURVES
• A plot of pH of analyte (base/acid) against
volume of titrant (acid/base) produces a
curve
• pH monitored by pH-meter
• A strong acid & strong base gives sharp
end-point, like one above
• Some examples of titration curves

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Titration of NaOH with H2SO4 14

Fewer moles of H2SO4

would be required to 7
neutralize 25 mL NaOH,
thus the curve would shift
0
left
0 25 50
Titration of HCl with NaOH
14
Because we start with
pure HCl, then add NaOH
the pH starts low then 7
goes high, thus the curve
flips
08/18/2023
0
K.K. Nyirenda 31
0 25 50
 Weak base with 14
strong acid
A weak base would lower the
“base” part of the curve (it’s 7
weak so it has a lower pH), thus
yielding a lower (acidic)
equivalence point 0
0 25 50
Strong base with 14
weak acid
A weak acid would raise the
“acid” part of the curve (it’s 7
weak so it has a higher pH),
thus yielding a higher (basic)
equivalence point 0
08/18/2023 K.K. Nyirenda 32
0 25 50
 Acids/bases that donate more than
one proton

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 a) CO32- + H+ HCO3-
b) HCO3- + H+ H2CO3

14 - -
a) CO23 + H
+
HCO3
12
10 Phenolphtalein
8
pH
6 b) HCO3
- + H
+
H2CO3
4
Methyl orange
2
0

ml of HCl added

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 Choosing an indicator
Selection of correct indicator depends on what type of acid /
base reaction is taking place:
• Strong acid (SA) + strong base (SB)
• Strong acid (SA) + weak base (WB)
• Weak acid (WA) + strong base (SB)
Three main indicators to choose from:
Indicator Acid Colour Base Colour pH Range Use

Phenolphtalein Clear Pink 8.3– 10.0 WA / SB

Bromothymol Yellow Blue 6.0– 7.6 SA / SB
blue
Methyl Orange Red Yellow 3.1– 4.4 SA / WB

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Strong acid, strong base
pH of base. All H+ used up so more
addition of OH just increased [OH] and
hence pH resembles that of OH

Neutralisation point. [OH-] = [H+]. Its

also called the inflection point

H+ ions just about to be finished.

pH of acid. As OH is added, the OH is

nuetralised, H+ ions from the acid
depleting slowly untli all H+ ions from
the acid are consumed.
Weak acid Strong Base
Note the circled regions and compare
with Strong acid/base titration curve

Equivalence point is above pH 7.

Remember CH3COO- + H2O ------
CH3COOH

Start pH is higher than Strong

acid/base. Why?
 Weak acid Weak Base
Strong acid Weak base
 Weak acid, and weak base

Strong acid and weak base