NNAMDI AZIKIWE UNIVERSITY AWKA

SCHOOL OF PHARMACEUTICAL SCIENCE AGULU

DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL CHEMISTRY

PMC 332 ASSIGNMENT

EZEUGWU BENITA UCHENNA

2020654063
TABLE OF CONTENTS

REDOX TITRATION

 Meaning
 Principle
 Examples
 Pharmaceutical Application

DRUG PROFILE (ACETAMINOPHEN)

 Background
 Nomenclature
 Structure
 Chemical formula
 Brand names
 Physical properties
 Physiochemical properties
 Chemical synthesis
 Method of assay
 Indications
 Mechanism of action
 Pharmacokinetics
 Dosage forms
 Adverse effects
 Contraindications
 Indications
REDOX TITRATION
MEANING

Redox titration is a type of chemical analysis where the reaction involves a transfer of
electrons between reactants. It typically measures the concentration of a substance by
titrating it with a solution of known concentration that can undergo a redox reaction.
The endpoint is determined by a change in the oxidation state of the reacting species.

PRINCIPLE

The principle of redox titration is based on the transfer of electrons between the
reacting substances. In a redox reaction, one substance undergoes oxidation (loses
electrons), while another undergoes reduction (gains electrons). The titration involves
adding a titrant of known concentration to the analyte until the reaction reaches its
endpoint, which is determined by a specific indicator or by monitoring a change in
potential (as in potentiometric titrations). The stoichiometry of the redox reaction
allows the calculation of the unknown concentration of the analyte. Redox reaction
involves reduction and oxidation reaction

A substance undergoes oxidation through

 Addition of oxygen atom

 Removal of hydrogen Atom
 Loss or donation of electrons
 An overall increase in the oxidation state of the substance

A substance undergoes reduction through

 Addition of oxygen
 Removal of hydrogen
 Accepting electron
 An overall reduction in the oxidation state of the substance

EXAMPLES OF REDOX TITRATION

An example of redox titration is the titration of potassium permanganate (KMnO4) against oxalic
acid (C2H2O4).

In this titration, the analyte is oxalic acid and the titrant is potassium permanganate. The oxalic
acid acts as a reducing agent, and the KMnO 4 acts as an oxidizing agent. Since the reaction takes
place in an acidic medium, the oxidizing power of the permanganate ion is increased. This acidic
medium is created by the addition of dilute sulfuric acid.

MnO4−+8H++5e−→Mn2++4H2O
KMnO4 acts as an indicator of where the permanganate ions are a deep purple colour. In this
redox titration, MnO4– is reduced to colourless manganous ions (Mn2+) in the acidic medium.
The last drop of permanganate gives a light pink colour on reaching the endpoint. The
following chemical equation can represent the reaction that occurs

Molecular equation
2KMnO4+3H2SO4→K2SO4+2MnSO4+3H2O+5[O]
H2C2O4.2H2O+[O]→2CO2+3[H2O]×5
Complete Reaction

2KMnO4+3H2SO4+5H2C2O4.2H2O→K2SO4+2MnSO4+18H2O+10CO2
Ionic equation

MnO4−+8H++5e−→Mn2++4H2O]×2
C2O42−→2CO2+2e−]×5
Complete Reaction

2MnO4−+16H++5C2O42−→2Mn2++8H2O+10CO2

Other examples include

 Iodine Titration: Determination of vitamin C content in a solution using iodine
as the titrant.

 Dichromate Titration: Quantifying the amount of ethanol in a solution by

titrating with potassium dichromate.
 Cerimetric Titration: Estimating the concentration of ferrous ions using ceric
ammonium sulfate as the titrant.

PHARMACEUTICAL APPLICATION OF REDOX TITRATION

Redox titrations find several applications in the pharmaceutical industry, including:

Drug Assay: Determining the concentration of active pharmaceutical ingredients

(APIs) in medications using redox reactions.

Stability Testing: Monitoring the oxidative stability of pharmaceutical formulations,

ensuring the quality and shelf life of drugs.

Antioxidant Analysis: Assessing the antioxidant properties of pharmaceutical

compounds by titrating against oxidizing agents.

Vitamin Analysis: Measuring the concentration of vitamins, especially vitamin C

(ascorbic acid), in pharmaceutical products using redox titration methods.

Trace Metal Analysis: Quantifying trace metals in pharmaceutical formulations,

ensuring compliance with regulatory standards.

These applications highlight the importance of redox titrations in ensuring the quality,
efficacy, and stability of pharmaceutical products.

DRUG PROFILE (ACETAMINOPHEN)

Acetaminophen, also known as paracetamol, is a widely used over-the-counter

analgesic (pain reliever) and antipyretic (fever reducer). Its chemical name is N-
acetyl-p-aminophenol.

BACKGROUND

 Discovery: Acetaminophen was first synthesized in 1877 by Harmon Northrop

Morse.
 Commercialization: It became commercially available in the 1950s and gained
popularity due to its effectiveness in pain relief without the anti-inflammatory
effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs).

 Mechanism of Action: While its exact mechanism is not fully understood, it is

believed to work by inhibiting an enzyme in the brain called cyclooxygenase
(COX), but primarily in the central nervous system, unlike NSAIDs which affect
peripheral COX enzymes.

 Usage: Commonly used to relieve mild to moderate pain and reduce fever. It is a
key ingredient in many combination products, such as cold and flu medications.

 Liver Metabolism: Acetaminophen is metabolized in the liver, and excessive use

or overdose can lead to liver damage. It's important to follow recommended
dosage guidelines to avoid potential toxicity.

 Global acceptance: It is widely accepted globally and is considered one of the

safest over-the-counter pain relievers when used appropriately.

Acetaminophen continues to be a mainstay in the management of pain and fever, but

users should be mindful of its dosage limits to prevent adverse effects.

NOMENCLATURE

The systematic chemical name for acetaminophen is N-(4-

hydroxyphenyl)ethanamide. It is commonly known by its generic name,
acetaminophen. The International Union of Pure and Applied Chemistry (IUPAC)
name reflects its chemical structure, indicating the substituent groups and their
positions within the molecule. In the case of acetaminophen, it consists of an amide
(ethanamide) linked to a hydroxyphenyl group at the para-position (4-
hydroxyphenyl). The more widely used and recognized name, acetaminophen, is often
preferred in general usage and pharmaceutical contexts.

STRUCTURE
CHEMICAL FORMULA

The chemical formula of acetaminophen is C8H9NO2.

BRAND NAMES

Acetaminophen is sold under various brand names depending on the region. Some
common brand names for acetaminophen include:

. Tylenol (North America)

. Panadol (International)
. Paracetamol (Generic name used in many countries)
. Calpol (United Kingdom and India)
. Aceta (United States)
. Mapap (United States)
. Feverall (United States)
. Tempra (United States and Canada)
These are just a few examples, and there are many other brand names for
acetaminophen products worldwide. It's important for individuals to be aware of the
specific brand names used in their region and to follow recommended dosage
guidelines for the particular product they are using.

PHYSICAL PROPERTIES OF ACETAMINOPHEN

 Appearance: Acetaminophen is a white, crystalline powder or solid.

 Melting Point: The melting point of acetaminophen is typically around 169-170

°C.

 Solubility: It is sparingly soluble in cold water but more soluble in hot water. It is
readily soluble in ethanol and slightly soluble in ether.

 Odor: Acetaminophen is odorless.

 Molecular Weight: The molecular weight is approximately 151.16 g/mol.

 Density: The density of acetaminophen is about 1.263 g/cm³.

Understanding these physical properties is crucial for pharmaceutical and chemical

applications, including formulation and manufacturing processes.

PHYSIOCHEMICAL PROPERTIES OF ACETAMINOPHEN

 Chemical Formula: C8H9NO2

 Molecular Weight: Approximately 151.16 g/mol

 pKa: The pKa of acetaminophen is around 9.5, indicating its weakly acidic
nature.

 Solubility: It is sparingly soluble in cold water but more soluble in hot water. It is
readily soluble in ethanol and slightly soluble in ether.
 Partition Coefficient (Log P): The logarithm of the partition coefficient (Log P)
for acetaminophen is approximately 0.42, indicating a tendency to be more
lipophilic than hydrophilic.

 Melting Point: The melting point is typically around 169-170 °C.

 pH: In its pure form, acetaminophen is generally considered neutral, but its
aqueous solutions can exhibit pH changes depending on concentration.

CHEMICAL SYNTHESIS OF ACETAMINOPHEN

The chemical synthesis of acetaminophen involves several steps. The most common method is
the acetylation of p-aminophenol. Here is a simplified outline of the synthesis:

 Starting Material: Begin with p-aminophenol (4-aminophenol), which has the

following structure:

 Acetylation: Acetylate the amino group (-NH2) of p-aminophenol by reacting it

with acetic anhydride (or acetyl chloride). This involves replacing the amino
hydrogen with an acetyl group (-COCH3). The reaction is catalyzed by an acid,
often sulfuric acid:
l
 Purification: The reaction mixture is then typically purified to isolate the
acetaminophen product. This can involve processes such as filtration or
crystallization.

 Final Product: The result of the synthesis is acetaminophen (N-(4-

hydroxyphenyl)ethanamide)

This synthesis outlines the conversion of p-aminophenol into acetaminophen through

acetylation. It's important to note that industrial processes may involve additional
steps and optimizations for efficiency and purity.

METHOD OF ASSAY

The method of assay for acetaminophen involves determining the quantity or

concentration of acetaminophen in a sample. Several analytical methods are
commonly employed for this purpose. One widely used method is high-performance
liquid chromatography (HPLC). Here's a simplified overview of an HPLC assay for
acetaminophen:

.
 Sample Preparation:Dissolve the sample containing acetaminophen in an
appropriate solvent.Filter the solution to remove any particulate matter.

 HPLC Analysis:Inject the prepared sample into the HPLC system.Use a suitable
mobile phase (often a mixture of water and organic solvent) to elute the
components of the sample through a chromatography column.The acetaminophen
in the sample will have a characteristic retention time.
.
 Detection:Employ a UV detector to monitor the eluent for the presence of
acetaminophen.Acetaminophen absorbs UV light at a specific wavelength,
allowing for its quantification.
.
 Calibration:Create a calibration curve by analyzing standards with Use the
calibration curve to relate the detector response to the concentration of
acetaminophen in the sample.

 Quantification:Quantify the amount of acetaminophen in the sample based on

the calibration curve.

Other methods for the assay of acetaminophen include spectrophotometry, capillary

electrophoresis, and titration techniques. The specific method chosen depends on
factors such as sensitivity, precision, and the equipment available in the laboratory.

INDICATIONS

Acetaminophen is commonly used for the relief of mild to moderate pain and as a
fever reducer. Its indications include:
 Pain Relief: Acetaminophen is effective in alleviating various types of pain,
including headaches, muscle aches, toothaches, and minor joint pain.

 Fever Reduction: It is used to lower fever associated with conditions such as

colds, flu, and other infections.

 Post-Vaccination Discomfort: Acetaminophen is often recommended to manage

pain and fever following vaccination.
 Pain Management in Chronic Conditions: It may be used as part of a pain
management plan for certain chronic conditions where NSAIDs (nonsteroidal
anti-inflammatory drugs) might be contraindicated.

 Pediatric Use: Acetaminophen is commonly used in children for pain and fever
relief, and it is often considered a suitable option for young patients.

It's important to note that while acetaminophen is widely used, exceeding the
recommended dosage can lead to severe liver damage. Users should follow dosage
instructions carefully and consult with healthcare professionals if they have specific
health concerns or conditions.

MECHANISM OF ACTION

The exact mechanism of action of acetaminophen is not fully understood, but it is

believed to involve both central and peripheral mechanisms. The primary site of
action is thought to be in the central nervous system, particularly in the brain.

Central Mechanism:

Inhibition of Prostaglandin Synthesis: Acetaminophen is believed to inhibit an

enzyme called cyclooxygenase (COX) in the brain. However, unlike nonsteroidal
anti-inflammatory drugs (NSAIDs) such as ibuprofen, acetaminophen's inhibition of
COX is thought to be more prominent in the central nervous system rather than in
peripheral tissues.

CNS-Specific COX Inhibition: Acetaminophen's preference for COX inhibition in

the central nervous system may explain its analgesic (pain-relieving) and antipyretic
(fever-reducing) effects without the significant anti-inflammatory actions seen with
NSAIDs.

Peripheral Mechanism

Limited Peripheral Anti-Inflammatory Effects: Acetaminophen has minimal anti-

inflammatory effects in peripheral tissues, which differentiates it from traditional
NSAIDs.

Weak Antiplatelet Activity: Unlike some NSAIDs, acetaminophen has weak

antiplatelet activity, making it less likely to cause bleeding issues.

It's crucial to note that despite its widespread use, the exact details of acetaminophen's
mechanism and its selectivity for COX in the central nervous system are still areas of
ongoing research. Additionally, acetaminophen's use should be within recommended
dosage limits to avoid potential adverse effects, especially liver damage associated
with overdose.

PHARMACOKINETICS
.
 Absorption: Acetaminophen is rapidly and almost completely absorbed from the
gastrointestinal tract, primarily in the small intestine. Peak plasma concentrations
are typically reached within 1-2 hours after oral administration.

 Distribution Acetaminophen has a moderate volume of distribution, distributing

throughout the body fluids. It does not bind extensively to plasma proteins.

 Metabolism:The majority of acetaminophen undergoes hepatic metabolism. The

main metabolic pathway involves conjugation with glucuronic acid and sulfate,
leading to the formation of inactive metabolites. A small portion undergoes
oxidation by cytochrome P450 enzymes to form a highly reactive intermediate,
N-acetyl-p-benzoquinoneimine (NAPQI).
.
 Detoxification of NAPQI:Normally, NAPQI is detoxified by conjugation with
glutathione in the liver.However, in cases of overdose, when glutathione is
depleted, NAPQI may cause hepatotoxicity by binding to cellular proteins.
.
 Elimination:The majority of metabolites are excreted in the urine, primarily as
glucuronide and sulfate conjugates. A small fraction is excreted unchanged in the
urine.
.
 Half-Life:The elimination half-life of acetaminophen is around 2 to 3 hours in
adults, but it can be prolonged in cases of overdose or in individuals with liver
dysfunction.

Understanding the pharmacokinetics of acetaminophen is crucial for determining

appropriate dosing regimens and recognizing the potential risks associated with its
use, particularly in cases of overdose. Monitoring liver function is essential, especially
in patients with pre-existing liver conditions.

DOSAGE FORMS

Acetaminophen is available in various dosage forms to cater to different patient

needs. Common dosage forms include:

 Tablets and Caplets: These are solid oral dosage forms with varying strengths of
acetaminophen, allowing for convenient oral administration.
 Liquid Formulations: Acetaminophen is available in liquid suspensions or
solutions, often suitable for pediatric use or for individuals who have difficulty
swallowing tablets.

 Chewable Tablets: These are tablets that can be chewed before swallowing,
providing an alternative for those who may have difficulty swallowing traditional
tablets.

 Dissolvable Tablets: Some formulations come in tablet form that dissolves

quickly in the mouth without the need for water.

 Suppositories: Acetaminophen suppositories are available for rectal

administration, useful in situations where oral administration is challenging, such
as in pediatric cases.

 Combination Products: Acetaminophen is commonly included in combination

with other active ingredients, such as decongestants or antihistamines, in over-
the-counter cold and flu medications.

 Intravenous (IV) Formulation: In hospital settings, acetaminophen can be

administered intravenously for patients who cannot take oral medications.

ADVERSE EFFECTS

While acetaminophen is generally considered safe when used at recommended doses,

excessive or prolonged use can lead to adverse effects, and overdose can be severe.
Common adverse effects and considerations include:

Liver Damage: Acetaminophen overdose can cause severe liver damage. The toxic
metabolite N-acetyl-p-benzoquinoneimine (NAPQI), produced during metabolism,
can overwhelm the liver's detoxification mechanisms.
Hepatotoxicity: In severe cases of overdose, acute liver failure may occur,
potentially leading to fatal outcomes.

Renal Effects: Prolonged high doses may contribute to renal impairment, but this is
less common compared to the potential for liver toxicity.

Allergic Reactions: While rare, allergic reactions such as skin rash or swelling may
occur. Seek medical attention if these symptoms occur.

Blood Disorders: Acetaminophen has been associated with rare cases of blood
disorders, including thrombocytopenia (low platelet count) and leukopenia (low white
blood cell count).

Interaction with Alcohol: Combining acetaminophen with alcohol can increase the
risk of liver damage.

Overdose Symptoms: Symptoms of acetaminophen overdose include nausea,

vomiting, loss of appetite, confusion, jaundice, and, in severe cases, unconsciousness.

CONTRAINDICATIONS

While acetaminophen is widely used, there are certain contraindications and

precautions that individuals should be aware of:
Liver Impairment: Individuals with liver disease or impairment should use
acetaminophen with caution, as excessive doses or prolonged use can lead to further
liver damage.

Alcohol Consumption: Chronic alcohol consumption combined with acetaminophen

increases the risk of liver damage. Individuals should avoid excessive alcohol intake
while using acetaminophen.

Allergy or Hypersensitivity: Individuals with a known allergy or hypersensitivity to

acetaminophen should avoid its use.

G6PD Deficiency: Glucose-6-phosphate dehydrogenase (G6PD) deficiency can be

associated with an increased risk of hemolysis (breakdown of red blood cells) when
using acetaminophen.

Interaction with Other Medications: Certain medications, including those that

induce or inhibit liver enzymes, may interact with acetaminophen. Individuals taking
multiple medications should consult with healthcare professionals to avoid potential
drug interactions.

Pregnancy and Breastfeeding: Acetaminophen is generally considered safe during

pregnancy and breastfeeding when used at recommended doses. However, it's
advisable for pregnant or breastfeeding individuals to consult with healthcare
professionals before using any medication.

INTERACTION

Acetaminophen can interact with other medications, and individuals should be

cautious, especially if they are taking multiple drugs. Some notable interactions
include:

Warfarin (Coumadin): Acetaminophen may increase the risk of bleeding when

taken concurrently with the anticoagulant warfarin.

CYP Enzyme Inducers/Inhibitors: Drugs that induce or inhibit cytochrome P450

(CYP) enzymes in the liver can affect the metabolism of acetaminophen. For
example, substances like rifampin (CYP inducer) can increase the production of toxic
metabolites, while inhibitors like certain antifungals can potentially lead to increased
acetaminophen levels.

Alcohol: Combining acetaminophen with alcohol may increase the risk of liver
damage, as both can place strain on the liver.
Antiseizure Medications: Certain antiseizure medications, such as carbamazepine
and phenytoin, may induce liver enzymes and affect the metabolism of
acetaminophen.

Other Analgesics: Combining acetaminophen with other analgesics, especially those

containing acetaminophen or other NSAIDs, can lead to unintentional overdose.
Always check the ingredients of combination medications.

Cholestyramine: Cholestyramine, used to lower cholesterol, may reduce the

absorption of acetaminophen if taken simultaneously.

Methotrexate: Concurrent use of acetaminophen and high doses of methotrexate may

increase the risk of methotrexate toxicity.