CENTRAL UNIVERSITY

SCHOOL OF PHARMACY
PHAD: 324 PHARMACEUTICAL TECHNOLOGY PRACTICAL
(MINI PROJECT)

TITLE
GRANULATION AND ENCAPSULATION OF IBUPROFEN,SUSPENSION AND
QUALITY CONTROL ON SOLID DOSAGE FORMS

2023/2024 ACADEMIC YEAR

SECOND SEMESTER
LEVEL 300

GROUP E (3)
NAMES OF STUDENTS INDEX NUMBERS
Jochebed Sarfo Manu DPH/21/01/0896
Karen Efua Komeh DPH/21/01/0503
Tanko Namneaya Samuel DPH/21/01/0074
Princess Eyiram Honu DPH/21/01/0651
Gabriel Belefune DPH/21/01/1378
TABLE OF CONTENT
CHAPTER ONE: TABLETING
Aim / Objectives
Problem Statement
Justification
Introduction
Literature Review
Methodology
Results and Analysis
Discussions
Recommendations
Conclusions
CHAPTER TWO: GRANULATION
Aim / Objectives
Problem Statement
Justification
Introduction
Literature Review
Methodology
Results and Analysis
Discussions
Recommendations
Conclusions
CHAPTER THREE: SUSPENSION
Aim / Objectives
Problem Statement
Justification
Introduction
Literature Review
Methodology
Results and Analysis
Discussions
Recommendations
Conclusions
CHAPTER FOUR: QUALITY CONTROL
Aim / Objectives
Problem Statement
Justification
Introduction
Literature Review
Methodology
Results and Analysis
Discussions
Recommendations
Conclusions
CHAPTER ONE: TABLETING
AIM
At the end of this project lab, students should be able to:
 Accurately calculate the amount of ingredients needed for preparing granules for
tableting.
 Appreciate the wet method of granulation in preparation of granules
 Appreciate pre compresssion factors which can affect the quality of compressed
tablets
 Operate a manual tableting machine
 Appreciate compression factors which can affect the qualty of compressed
tablets.

OBJECTIVES
 Appreciate pre compression and compression factors which can affect the quality
of compressed tablets.
 Appreciate the various quality control tests and reconcile pharmacopoieal
specifications with their practical findings and make scientific deductions as well
as conclusions.
PROBLEM STATEMENT
1. High weight and dose variation of the tablets
2. Check die volume and compression force, poor flow of granules, different
granule sizes/densities
3. Low mechanical strength of the tablets
4. Check compression force
5. Chipping
6. Check machine settings, dry granules, excess binder
7. Capping and lamination of the tablets
8. Adhesion or sticking of powder material to punch tips – poor lubrication, wrong
choice of lubricant, film of fines
9. High friction during tablet ejection
10. Protracted disintegration – strong granulating agent, high degree of compaction
(hard tablets), hydrophobicity (lubricant), wrong or inappropriate/inadequate
11. Drug instability – dry air, moisture content of granules
JUSTIFICATIONS
Due to the presence of the different types of tablets, there is a likelihood of poor
formulation of tablets. Hence it is essential that quality control tests are carried out on
tablets which are meant for the local market and public use to check if they fall within
regulation specifications and guidelines.

INTRODUCTION
Tablets are solid dosage forms containing one or more medicinal substances with or
without added pharmaceutical ingredients. Tablets are the most widely patronized oral
dosage forms. They may vary in size, shape, weight, hardness, disnitegration and
dissolution, characteristics and in other aspects, depending on their intended use and
methods of manufacture. Tablets are prepared primarily by compresion, with a limited
numer prepared by moulding. Compresed tablets are manufactured with tablet
machines capable of exerting great pressure in compacting the powdered or
granulated material(which contains a drug and certain excipients selected to aid in
processing and to improve product properties). their shpe and dimensions are
determined by the use of various shapes punches and dies. Tableting machine also
refers to us pharmaceutical tablet press, tableting compressing machines or tablet
punching machines. Tablet press in current use can be classified into : single punch
and multy station. The single punch tableting machine is use in this lab session.
Quality control refers to the sum of all procedures undertaken to ensure that the
performance of a product is within the specifications stated by the pharmacopoeia
monograph (Newton,2003). Quality control of tablets is the systematic determination
of the physical, chemical, mechanical, biological or microbial properties of tablets on
the basis of pharmacopeial standards such as British pharmacopoeia united states
pharmacopoeia etc(Krycer et al., 1983). To design the perfect tablets and later monitor
tablet production quality, quality control test of tablets must be essential. Quality
control testing has benefits to both the consumer and the pharmaceutical company
manufacturing the drug(Faure et el., 2001).
To the consumer, quality control testing ensures that the drug taken is safe and does
not cause any harm to the consumer. That is no toxic effects will come to the
consumer when he or she takes the drug (McConville et al., 2004).
To the manufacturer, the importance of quality control testing ensures public safety.
That is any pharmaceutical company’s ultimate goal is to provide a product that will
keep the public safe. A well-made drug has the ability to significantly improve
someone’s life. Creating a high-quality product has a significant impact on society’s
general health and well-being (McConville et al., 2004).
Also, to comply with regulations, the pharmaceutical industry is one of the most
heavily regulated industries in the world. Quality control is essential for ensuring
compliance with all regulations, both in the country of manufacture and in the
countries where the drugs will be sold (McConville et al., 2004).
For tablets, the quality control requirements include the pharmacopeial or official test
and the non- pharmacopeial or non- official test. The official test include; uniformity
of weight, Uniformity of content, thickness, disintegration dissolution tests and the
unofficial test include the hardness and friability tests (Becker et al., 1997).
Uniformity of weight is defined as the test performed by weighing individually about
twenty tablets randomly selected from a tablet batch and determining their individual
weights and the individual weights are compared with the average weight (Krycer et
al, 2010).
Uniformity of content test is the test that evaluates the equality of the dosage of a
pharmaceutical drug (Krycer et al, 2010).
Thickness test is the test to determine the diameter of the tablet. It is done using the
vernier caliper.
The disintegration test is the time needed for a certain number of tablets to break
down into smaller particles. This test is a pharmaceutical method developed to
evaluate and ascertain how long a tablet can be dissolved in the human body or
digestive tract characterized by the preparation being dissolved, dispersed, or softened
(Krycer et al, 2010).
Dissolution testing measures the extent and rate of solution formation from a dosage
form, such as tablet, capsule, ointment, etc. The dissolution of a drug is important for
its bioavailability and therapeutic effect (Bauer et al, 2012).
Hardness test is defined as the force required to break a tablet in a diametric
compression test (Jachowicz, 2013).
Friability test is the measure of the tendency of a tablet to lose component particles
due to abrasion, friction or mechanical shock (Prescott and Hoss field,2012).

LITERATURE REVIEW
According to the medicinal dictionary,a tablet is a solid dosage form containing a
medicinal substance with or without a suitable diluent ; it may vary in size , shape and
weight, may be classified according to the method of manufacture such as compressed
tablets. Pharmaceutical tablets are solid dosage forms consisting of ingredients and
suitable excipients.
According to the international pharmacopoeia, tablets are solid dosage forms usually
obtained by single or multiple compressions of powder or granules. In certain cases
tablets may be obtained by mounding or extrusion techniques.
According to pharma- tips, tablets are solid dosage forms each containing a unit dose
of or more medicament.
Examples of main excipients used in tablets are:
1. Diluent: increase the mass of the formulation products and enable accurate
dosing of potent drugs. Examples include, lactose,glucose,
sorbitol ,dextrin ,silicate,calcium and magnesium salts and many more.
2. Binder: bind the tablet ingredients together,giving strength and form.
Examples are mainly natural or synthetic polymers,of which starch cellulose
derivatives,sugar alcohols and sugars.
3. Disintegrants : aid the dispersion of the tablet in the gastrointestinal
tract ,releasing the active ingredient and increasing surface area for dissolution.
Compounds which swells or dissolve in water (starch,cellulose derivatives,alginates
and crosprovidone ) make good disintegrants in tablet formulation.
4. Glidants : improve the flow of powders during tablet manufacturing by
reducing friction and adhesion between particles and die cavity. They are also used as
anti-caking agents. Colloidal anhydrous silicon, silica compounds and talc are
examples of glidants.
5. Lubricants : during compression lubricants act at the interface between the
face of the die and the surface of the tablet and act to reduce the friction at this
interface during ejection of the tablet from the tablet press. Examples include
magnesium stearate,stearic acid ,talc.

Other recipients are sweeteners or flavors to mask bad tasting active ingredients and
colourants or pigments to make uncoated tablets visually attractive.

TYPES OF TABLETS
Coated tablets
A type of tablet usually made by enclosing a drug in a protective shell. Usually,
tablets are coated to;
1. Hide the taste of the tablets components
2. Make the tablet smoother and easier to swallow.
3. Extend the shelf life.
4. Make it more resistant to environmental changes.

Types of tablets based on coating

1. Sugar coated tablets
2. Film coated tablets
3. Enteric coated tablets
Buccal and sublingual tablets
1. Effervescent tablets
2. Chewable tablets

Types of tablets based on release profile

1. Fast release tablets
2. Regular release tablets
3. Delayed release tablets
4. Layered tablets

GENERAL PROPERTIES OF TABLETS

A tablet must be strong and hard to withstand mechanical shock during
1. Manufacturing, packing, shipping, dispensing and use.
2. The drug content of the tablet must be bioavailable that is,the tablet must be
able to release it content in a predictable and reproducible manner.
3. The tablets must be chemically and physically stable to maintain its chemical
and physical attributes during manufacture,storage, and use.
4. The tablet should have elegant product identity which is free from any tablet
defect.
5. Tablets must be uniform in weight and in drug content.Is the term used when
the upper or lower segment of the tablet seperates horizontally, either partially or
completely from the main body of a tablet and comes off as a cap.
6. Causes:
7. Large amount of fines in the granules.
8. Too dry or very low moisture content in granules.
9. Not thoroughly dried granules.
10. Insufficient amount of binder or improper binder.
11. Granular mass too cold to compress firmly.
12. Unpolished punch and die surfaces.
CAPPING
Is the term used when the upper or lower segment of the tablet seperates horizontally,
either partially or completely from the main body of a tablet and comes off as a cap.
Causes:
Large amount of fines in the granules.
Too dry or very low moisture content in granules.
Not thoroughly dried granules.
Insufficient amount of binder or improper binder.
Granular mass too cold to compress firmly.
Unpolished punch and die surfaces.

LAMINATION
Is the separation of a tablet into two or more distinct horizontal layers.
Causes:
Air entrapment during compression and subsequent release on ejection.
Too much of hydrophobic lubricant. eg. magnesium stearate.
Rapid decompression
TABLET COATING
Tablet coating is the application of a coating material to the exterior of a tablet with
the intention of conferring benefits and properties to the dosage form over the
uncoated variety.
Reasons for tablet coating:
Protecting the drug from degradation by air, moisture and light in order to improve
stability.
Masking unpleasant taste and odour
Making it easier for the patient to swallow the tablet
Improving product identity
Facilitating handling especially in high speed packaging or filling lines.
Improve product appearance
Modifying drug release as in enteric-coated, repeat-action and sustained-release
products.
To target drug release to a specific site in the GIT.
Main stages of coating:
 The tablets are placed in the coating apparatus and agitated.
 The coating solution is sprayed onto the surface of the tablets.
 Warm air is passed over the tablets to facilitate removal of the solvent from the
adsorbed layer of coating solution on the surface of the tablets.
 When the solvent has evaporated, the tablets will be coated with the solid
component of the original coating material.
COATING FORMULATION
Two main formulation types:
Solutions
Emulsions

Typically comprises of
Polymer – used to make the film. e.g. HPMC, MC, HPC, methacrylate copolymers
(Eudragit – L, S, FS, and E ---- RS and RL)

Plasticizer – used to increase flexibility in the coating, reduce film cracking and
improves adhesion of the film to the tablet. e.g. glycerin, propylene glycol,
polyethylene glycol, triacetin, phthalate esters

Colourants – to improve appearance and facilitate product identification. e.g. Iron

oxides, caramel, carotenoids, flavones, tartrazine, sunset yellow, erythrosine,
amaranth,
Solvent – aid in the application of the coat to the tablet surface e.g alcohols, ketones,
esters, chlorinated hydrocarbons, water
SUGAR COATING
- This imparts a smooth, rounded and elegant appearance to the tablet.
-Sugar-coating relies primarily on the use of sucrose.
The sugarcoating of tablets may be divided into the following steps:
waterproofing and sealing: the sealing coat is applied to the tablet to separate the
tablet ingredients from water. It is also to strengthen the tablet core. e.g. using
alcoholic solutions of shellac, gelatin, acacia, cellulose acetate phthalate or polyvinyl
acetate phthalate.
Sub-coating: this is the critical operation in sugar-coating. Gum solutions (sucrose +
acacia/gelatin) are mostly applied and weight build-up is done at this stage as
well as uniform edges.

smoothing and final rounding: this is usually accomplished by the application of a

simple syrup solution (60-70%).
finishing and coloring if desired: Dyes or pigments are used.
Polishing: sugar-coated tablets are dull in appearance and thus require polishing to
achieve final elegance. Waxes (beeswax, carnauba wax, candelila wax or hard
paraffin) are used.
Printing: this is branding with inks.
FILM COATING
The sugar-coating process is tedious, time-consuming, and requires the expertise of
highly skilled technicians.
It results in coated tablets that may be twice the size and weight of the original
uncoated tablets,
Sugar-coated tablets may vary slightly in size from batch to batch and within a
batch.
The film-coating process places a thin, skin-tight coating of a plastic-like material
over the compressed tablet. Film-coated tablets have essentially the same weight,
shape, and size as the originally compressed tablet.
The coating is thin enough to reveal any identifying monograms embossed in the
tablet during compression by the tablet punches.
 Film-coated tablets are also far more resistant to destruction by abrasion than are
sugarcoated tablets.
Film-coating solutions may be non-aqueous or aqueous. The non-aqueous solutions
contain
A film former – ethylcellulose, PVP
A plasticizer
A surfactant
Opaquants and colorants

METHODOLOGY

MATERIALS
Granules were prepared using the following substances: paracetamol, cornstarch,
acacia powder and lactose, weighing balance,steelco drying oven mortar and pestle,
stainless 316L wire mesh sieve,and funnel.

METHOD
PREPARATION OF BINDER
10 grams of the acacia powder was weighed into the mortar, 25ml of water was
measured and then added to the acacia powder in the mortar and triturated, till a
pourable mixture is formed. The solution was transferred into a measuring cylinder
and topped up with the rest 25ml of water.

PREPARATION OF GRANULES
22.5 grams of metronidazole powder was weighed, 4.95 of starch was also weighed to
be used as disintegrant , 62.55 grams of lactose were also weighed and 11ml of the
prepared binder.
The powders were ground to a smaller particles using the mortar and pestle adding the
powder in geometric dilution form (from the lowest mass to highest mass). The
mucilage was added in a bit to the powder mixture and kneaded continuously to
obtain a damp mass , the volume of mucilage used was 11mL. The kneaded powder
was sieved with sieve number eight ( wet screening) and the granules were obtained
was weighed and dried in a steelco drying oven over 60 degrees for 30 minutes, the
drying process was monitored periodically until about 20 minutes when the sample
completely dried. The sample were taken out from the oven and it weight was
determined again after the drying and it was realized that the weight was reduced.

The powder was divided into two parts and one was used for particle size analysis and
the other for compression into tablets
METHOD FOR SIEVING
 A stack or a nest of sieves are arranged with sieve with the lowest aperture size
to the largest aperture size.

 The sieves are stacked onto the Retsch Mechanical Shaker.

 The dried granules are weighed transferred unto the first sieve (Usually sieve
No. 8).
 The sieves are fitted unto the Retsch Mechanical Shaker and the amplitude and
time for agitation is set.
 After the time of agitation elapses, the sieves are removed.
The granules retained on each sieve is weighed and recorded.

TABLETING MACHINE
MASTER FORMULA TABLE
INGREDIENTS MASTER FORMULA SCALED QUANTITIES
(X450)
API(Metronidazole) 50mg 22.50g
Disintegrant(starch) 11mg 4.95g
Diluent(lactose) 139mg 62.55g
Binder(acacia) 1260mg 2.80g

CALCULATIONS
API(Metronidazole)=50mg
Scaled factor = amount to be prepared
Amount in master formula
Scaled factor = 450
1
=450
API = 50mg
Scaled quantity = 50mg x 1g x 450
1000mg
=22.5g
Disintegrant = 5.5% w/w
Scaled factor = 5.5g x 200mg
100g
= 11mg x 1g x 450
100mg
= 4.95g
Diluent
Lower di-volume = Api +disintegrant+diluent
200mg = 50mg +11mg+diluent
Diluent = 200mg-61mg
Diluent= 139mg
Scaled quantity = 139mg x1gx450
100mg
= 62.55g
Binder = 20%w/v
20g = 100ml
X = 50ml
X=50ml x 20g
100ml
=10g

PARTICLE WEIGHT UNIFORMITY TABLE

Number of tablets Weight(g) Deviation %Deviation

1 0.12 0.007 6.19
2 0.13 0.017 15.04
3 0.11 -0.003 -2.65
4 0.12 0.007 6.19
5 0.11 -0.003 -2.65
6 0.14 0.027 23.89
 7 0.10 -0.013 -11.50
8 0.11 -0.003 -2.65
9 0.11 -0.003 -2.65
10 0,11 -0.003 -2,65
11 0.10 -0.013 -11.50
12 0.13 0.017 15.04
13 0.11 -0.003 -2.65
14 0.10 -0.013 -11.50
15 0.10 -0.013 -11.50
16 0.11 -0.003 -2.65
17 0.11 -0.003 -2.65
18 0.13 0.017 15.04
19 0.10 -0.003 -11.50
20 0.11 -0.003 -2.65

DEVIATIONS
Mean = 0.113
Deviation = Weight - Mean
Tablet 1
D=0.12-0.113
= 0.007
Tablet 2
D = 0.13-0.113
= 0.017
Tablet 3
D = 0.11-0.113
= -0.003
%DEVIATIONS
%D = D x 100
Mean
Tablet 1
%D = 0.007 x100
0.113
 =6.19%
Tablet 2
%D = 0.017 x100
0.113
= 15.04%
Tablet 3
%D = -0.003 x 100
0.113
= -2.65%
PARTICLE SIZE ANALYSIS -SIEVING
Sieve Apert Range of Midpoi Weight Percent Cummulati Cummulati
Num ure Aperture( nt of of age ve % ve %
ber Size(u um) Range( granule weight Oversize Undersize
m) um) s(g) retaine
d
10 1700 >1700 _ 0 0 0 93.55
250 62 62-1700 881 18.47 92.35 92.35 93.55
350 45 45-62 53.5 0.24 1.2 93.55 1.2
450 32 32-45 38.5 0 0 93.55 0
500 25 25-32 28.5 0 0 93.55 0
600 16 16-25 20.5 0 0 93.55 0

A GRAPH OF %CUMMULATIVE OVERSIZE AGAINST MIDPOINT

CALCULATIONS INVOLVING THE GRAPH

MEAN SURFACE AREA

Logds = Logdgeo - 4.6052Log2θgeo

Θgeo = d84/d50

θgeo = 5.6x102/2.6x102

Θgeo = 2.1538

Dgeo =d50

Logds = Log(2.6x102) - 4.6052Log(2.1538)2

Logds = 1.9037

Ds =101.9037

Ds =80.11245
MEAN VOLUME

Logdv = logdgeo - 3.4539Log2θgeo

Logdv = Log(2.6x102) - 3.4539Log(2.1538)2

Logdv = 2.0315

Dv =102.0315

Dv =107.5230

DISCUSSION

DISCUSSION
In other to ensure that safe and effective medicines are given to a patient, particle size
analysis are carried out. Particle size analysis is an essential operation in the
pharmaceutical industry. A successfully formulated tablet must be marketed safe
and a therapeutically active formulation with consistent and predictable
performance. Particle size analysis which are performed during the manufacturing of
a pharmaceutical product include thickness, hardness, friability, dissolution time,
disintegration time. In process quality control test is necessary to ensure the safety of
finished pharmaceutical product.
The aim of the experiment was to conduct a particle size analysis on metronidazole
tablet. That is both the official.The particle size analysis includes uniformity of weight
test and sieving analysis
The reason for the conduction of uniformity of weight of the tablets was to determine
if each tablet contains the same amount of active ingredients and excipients. Also, to
determine if the weight is uniform. if the weight is not uniform some tablets may
contain too much or too little of the active ingredient which may lead to overdosing or
underdosing.
According to the United States Pharmacopoeia, the percentage deviation or difference
of a tablet whose average weight is more than 324mg is five percent and also
according to the British Pharmacopoeia more than 250mg average weight is also five
percent. According to both standards, not more than two (2) tablets should deviate by
the stated percentage and none should deviate by twice the stated percentage.
Comparing the results obtained to that of standard, the prepared or formulated
metronidazole tablets in laboratory did not fall within the standard pharmacopoeia
that is( BP). This may due improper preparation of binder, insufficient binder in
preparation of granules and also may be lack of skins in operating the machine or the
faulty machine.
sieving analysis
mean surface is to determine how the granules will interact with the environment
and the mean volume is to determine how well the granules packed for tableting.
From the experiments the results obtained was 80.112445 that is for the mean surface
and mean volume was 107.5230.

Conclusion
Both uniformity of weight and sieve analysis failed comparing to the standard
pharmacopoeia and therefore should not be accepted into the market.

ENCAPSULATION

AIM:

 To encapsulate a model drug using dry granulation and evaluate the process
efficiency.

SPECIFIC OBJECTIVES :

● To prepare drug-loaded granules using the dry granulation technique.

● To determine the Hausner Ratio and Carr's Index of the prepared granules,
characterizing their flow properties.
● To fill capsules with the prepared granules.
● To operate a manual capsule filling machine
 ● To evaluate the weight uniformity of the filled capsules.

PROBLEM STATEMENT:

Defects in the formulation and encapsulation of drugs may arise as a result of various
circumstances encountered during production as well as from improper product
handling and storage(Podczeck & Jones, 2004). The delivery of drugs in their pure
form often presents challenges that hinder their therapeutic efficacy and patient
compliance. Several Active Pharmaceutical ingredients exhibit low solubility in
aqueous environments, hindering their absorption and therapeutic efficacy.
Additionally, exposure to environmental factors such as light, oxygen, and moisture
can lead to API degradation, compromising drug potency and stability. Moreover,
conventional drug delivery often lacks specificity and control over release kinetics,
resulting in suboptimal treatment outcomes and potential side effects.

Flow ability issues, inadequate amount of excipients, capsule strength, usage of the
wrong capsule shell for a particular medication and weight differences may also pose
as challenges encountered during Encapsulation. Some defects faced in capsule
formulation are as follows:

1. Lumpy or misshapen capsules: This is as a result of the capsules forming

lumps or is otherwise misshapen.
2. . Improper rectification: This refers to when the capsules are not being
oriented properly (cap up).
3. Failure to separate: This results when the caps and bodies fail to separate.
4. Dented capsules: Dents can form on the dome of the cap and/or body for a
variety of reasons. One cause is improper setup that leads to the machine
applying excessive pressure.
5. Telescoping: This defect occurs when the cap and body misalign and the
capsule body splits and a portion of it covers the cap.
6. Popping: If the capsules open or elongate after filling, it's likely due
excessive locking pressure or overfilling. It's also possible that the locking
mechanism is weak, but that's a defect rarely seen in capsules supplied by
reputable manufacturers.
 Brittleness: This is as a result of when capsules lose moisture often due to poor
storage hence they become brittle

JUSTIFICATION

Orally given drugs are, without a doubt, the world's primary method of
pharmaceutical administration. According to Kiplinger, eight of the top fifteen best-
selling medications in 2017 were oral solid dosage (OSD) formulations, including the
top seller. Despite the growing popularity of parentally delivered biologics, many
patients find injections to be unpleasant and inconvenient. OSD forms continue to be
the favored administration method for developers owing to its low cost, convenience
of manufacture, and large range of patient-friendly dosage choices. For these reasons,
a rising number of oral dosage forms are being authorized and developed. OSDs
accounted for 53% of all novel molecular entities (NMEs) authorized by the FDA in
2018. This proportion of OSD approvals was greater than in the preceding two years
(50% in 2017 and 32% in 2016). Furthermore, whereas compressed tablet forms now
dominate OSD medications in general, encapsulated therapies constitute a close
second. This is mostly due to the fact that, encapsulating active components is
regarded as a dependable method of distributing very powerful APIs as well as other
compounds. Encapsulation offers compelling solutions to these challenges by
providing a protective barrier around APIs, enhancing their solubility, stability, and
targeted delivery. By encapsulating drugs within carriers or matrices, pharmaceutical
formulations can improve API bioavailability and protect against degradation, thereby
extending shelf life and maintaining therapeutic effectiveness. Furthermore,
encapsulation enables the development of controlled release formulations that
optimize drug delivery, ensuring sustained therapeutic levels in the body while
minimizing adverse effects and enhancing patient compliance. These advantages
underscore the critical role of encapsulation in advancing pharmaceutical technologies
and improving patient outcomes.

INTRODUCTION:

Drug delivery systems play a crucial role in modern medicine. They influence the
therapeutic efficacy and safety of drugs by controlling their release and absorption
within the body. Encapsulation of drugs represents a pivotal advancement in
pharmaceutical science, offering innovative solutions to enhance drug delivery,
efficacy, and patient outcomes. This technology involves the incorporation of active
pharmaceutical ingredients (APIs) into protective carriers or matrices, which range
from nanoparticles and liposomes to polymeric microspheres and dendrimers. These
carriers not only shield the drug from degradation and premature release but also
facilitate targeted delivery to specific tissues or cells within the body. To put it in
another way, Encapsulation is the act of enclosing medication’s solid or liquid dosage
form into a comparatively stable shell known as capsule making it easier for patients
to swallow (MRPharmS, 2007).

The Latin word "capsula" (which means small box) is where the term "capsule"
originates. Typically constructed of gelatin or other appropriate materials, capsules are
pharmaceutical dosage forms that contain a solid or liquid drug composition inside of
an exterior shell or coating. However, other polymers such as hydroxypropyl
methylcellulose (HPMC), polyvinyl alcohol (PVA), seaweed, or starch can also be
used to create the shell, in addition to gelatin. Capsules can be categorized as soft or
hard depending on the composition of the shell. Soft gels, commonly referred to as
soft gelatin capsules, are produced from gelatin film that is substantially more flexible
and plasticized than hard gelatin capsules. The ingredients of hard gelatin capsules,
also referred to as dry-filled capsules, include gelatin, a colouring agent, and
opaquant. There are multiple sizes and capsule numbers for the hard gelatin capsules.
Hard gelatin capsules are cylindrical in shape, while soft gelatin capsules come in
round, oval, and tube-like shapes. The body and cap of a hard gelatin capsule are
separate components, whereas the body and cap of a soft gelatin capsule are one piece
once the two portions of the capsule have been sealed. There are different capsule
filling machines and they include; hand operated machines, semi-automatic capsule
devices and automatic filling machines.

Central to the success of drug encapsulation is the preparation of granules that exhibit
optimal properties such as flowability and compressibility. Granulation methods like
wet granulation, involving liquid binders, and dry granulation, utilizing compaction
techniques, play crucial roles in achieving these properties. These methods prepare the
granules for encapsulation by improving their handling characteristics and facilitating
uniform distribution within capsules or tablets.

The primary goals of drug encapsulation include improving drug solubility,

bioavailability, and stability, thereby optimizing therapeutic efficacy while
minimizing side effects. Different encapsulation techniques, such as
nanoencapsulation and microencapsulation, cater for diverse drug properties and
delivery needs. In addition to enhancing drug delivery, encapsulation technologies
play a crucial role in overcoming physiological barriers such as the blood-brain
barrier (BBB) and improving the pharmacokinetic profile of drugs.

This project focuses on exploring the encapsulation of drugs using the dry granulation
method, emphasizing the significance of weight uniformity, flowability, and the
evaluation of Hausner Ratio, Carr’s Index and Angle of Repose. By systematically
evaluating these parameters, the project aims to develop a robust and reliable
encapsulation process that enhances drug stability, bioavailability, and therapeutic
efficacy. Ultimately, it contributes to advancing pharmaceutical technology, ensuring
safer and more effective drug delivery systems tailored to meet diverse patient needs.

CHAPTER TWO (2)

LITERATURE REVIEW:
This section provides an overview of relevant research on drug encapsulation,
granulation techniques, and the significance of flowability in capsule filling.
Drug encapsulation a critical area of research and vital technology in pharmaceutical
sciences, aims at enhancing the delivery, efficacy, and safety of therapeutic agents.
There are several Encapsulation methods used in Pharmaceutical
Technology(Sonawane et al..,2020). These methods offer diverse ways to encapsulate
drugs to achieve desired drug delivery profiles and enhanced stability. Enlisted below
are some methods;
1. Liposome Encapsulation: liposomes are spherical vesicles with a phospholipid
bi-layer which are used to encapsulate both lipophilic and hydrophilic drugs.
They are prepared by hydration of a lipid film followed by Sonication or
extrusion. Liposomes can improve drug delivery by enhancing solubility,
protection from degradation and facilitating targeted delivery to specific
 tissues or cells.
2. Nanoparticle Encapsulation: Nanoparticle encapsulation has emerged as a
revolutionary approach in drug delivery, offering several advantages over
traditional techniques. Nanoparticles are particles in the range of 1-100
nanometers (nm) providing a unique platform for encapsulating drugs,
enhancing stability and their therapeutic efficacy, controlled rease and
targeted delivery. Techniques for formulation include Nano precipitation,
emulsion methods or nanoparticle coating.
3. Microparticle Encapsulation: This process involves enclosing active
ingredients within micro sized particles or capsules typically ranging from 1-
1000 micrometers. This technique improves stability, masking unpleasant taste
and controlling release. Methods used in Microparticle encapsulation include
spray drying, solvent evaporation and emulsion polymerization.

Granulation methods:
Granulation is a crucial step in the preparation of solid dosage forms aimed at
improving flow ability, homogeneity and compression of powders. The two primary
methods of granulation are Wet granulation and Dry granulation each with specific
advantages and disadvantages.
Wet granulation involves the addition of a liquid binder to the powder blend, forming
granules through the agglomeration of particles. This method improves powder
flowability and compressibility but is unsuitable for moisture-sensitive or heat-labile
drugs due to the involvement of liquid and drying steps (Parikh, 2017) .
Dry granulation, in contrast, does not require liquid binders, making it ideal for
moisture-sensitive APIs. It involves the compaction of the powder blend into dense
slugs or sheets, which are then milled into granules. Roller compaction and slugging
are common techniques in dry granulation. This method is simpler, faster, and more
cost-effective than wet granulation, while also maintaining the chemical stability of
the API (Mackaplow, 2007) .

Role of Excipients in Granulation and Their Selection Criteria

Excipients play a critical role in the granulation process, influencing the flowability,
compressibility, and stability of the granules. In granulation, selecting appropriate
excipients is vital to achieve desirable physical properties and ensure the efficacy of
the final product.
Binders such as microcrystalline cellulose and lactose enhance the cohesiveness of the
powder blend, improving the mechanical strength of the granules (Pitt, 2013) .
Lubricants like magnesium stearate improve flowability and prevent sticking during
compression, facilitating smoother processing (Jivraj et al., 2000) . Disintegrants such
as croscarmellose sodium promote rapid granule breakup upon administration,
ensuring quick drug release and absorption (Saha & Shahiwala, 2009) .
The selection of excipients is based on their compatibility with the API, their ability to
improve the physical properties of the granules, and their impact on the final product's
stability and bioavailability (Augsburger & Hoag, 2008) .

Importance of Flowability for Capsule Filling Efficiency

Flowability is a critical parameter in the manufacturing of capsules, as it affects the
uniformity and consistency of the fill weight. Poor flowability can lead to uneven
filling, segregation, and operational issues during the encapsulation process.

Flowability is commonly assessed using indices such as the Hausner Ratio, Angle of
Repose and Carr's Index.

HAUSNER RATIO
The Hausner Ratio is the ratio of tapped density to bulk density, with lower values
indicating better flowability. Hausner ratio was related to friction between particles:
● The powder with low inter-particle friction, such as coarse spheres (good
flowability: Value less than 1.25).
● Value greater than 1.5 indicates poor flow. Applies to more cohesive, less free-
flowing powders such as flakes.
● Between 1.25 and 1.5, added glidant normally improves flow.
● > 1.5 indicates very poor flow and adding a glidant doesn’t improve flow.

ANGLE OF REPOSE
A relative simple technique for estimating the flow properties of a powder. It can
easily be determined by allowing a powder to flow through a funnel and fall freely
onto a surface. The height and diameter of the resulting cone are measured and the
angle of repose calculated as:
tan Ѳ = h/r
h is the height of the powder cone and r is the radius of the powder cone
1. Angle of repose less than 20º (Excellent flow).
2. Angle of repose of 20 - 30º (Good flow).
3. Angle of repose of 30-40º (Pass flow).
4. Angle of repose greater than 40º (Poor flow).
• The rougher and more irregular the surface of the particles, the higher will be
the angle of repose.

CARR’S COMPRESSILBILITY INDEX

The percentage compressibility of a powder is a direct measure of the potential
powder arch or bridge strength and stability and is calculated as

Relationship between powder flowability and % compressibility

FLOW DESCRIPTION % COMPRESSIBILITY

Excellent flow 5 – 15

Good flow 16 – 18

Fair flow 19 – 21

Poor flow 22 – 35

Very poor flow 36 – 40

Extremely poor flow

UNIFORMITY OF WEIGHT TEST

The standard according to the British Pharmacopoeia states is under the condition that
not more than two (2) tablets should deviate by the stated percentage and none should
deviate by twice the stated percentage.

AVERAGE WEIGHT %DIFFERENCE

Less than 300mg ±10

300mg or more ±7.5

Advantages of Encapsulation:
● Easy swallowing: capsules are generally easier to swallow compared to
tablets, especially for individuals who have difficulty swallowing solid forms.
They have a smooth, slippery surface and can be swallowed with water or
other liquids.
● Masking taste and odour: Capsules can effectively mask the taste and odour of
drugs, particularly for drugs that have an unpleasant taste or odour. The outer
shell covers the drug, preventing direct contact with taste buds and reducing
the chance of sensory perception.
Flexibility in formulation: Capsules can accommodate a wide range of drug
formulations including powders, granules, pellets, and liquids. This flexibility
allows for the formulation of drugs with different characteristics, such as
sustained-release formulations or combinations of multiple active ingredients.
● Stability and protection:The encapsulation of drugs in capsules provides
protection against environmental factors, such as light, moisture, and oxygen.
This helps to maintain the stability and integrity of the drugensuring its
potency and effectiveness throughout its shelf life. Accurate dosing: Capsules
are available in a variety of sizes allowing for precise dosing of
medications.This is particularly important for drugs with narrow therapeutic
ranges or when specific doses need to be administered.

Disadvantages of Encapsulation:
● Limited compatibility with certain drug formulations: Capsules may not be
suitable for all types of drug formulations. For example, drugs that are highly
hygroscopic (absorb moisture) or chemically unstable in the presence of water
may not be appropriate for encapsulation in capsules. Additionally, drugs that
require specialized release mechanisms, such as osmotic or ion-exchange
systems, may not be easily formulated as capsules.
● Manufacturing complexity: Capsule production can be more complex and
time-consuming compared to other dosage forms, such as tablets. The process
involves filling the drug formulation into the capsules, which requires precise
 equipment and controls to ensure accurate dosing.
Cost considerations: Capsules can be more expensive to manufacture compared to
other solid dosage forms, such as tablets. The encapsulation process, including the
production of the shell or coating, adds complexity and this in turn adds cost to the
manufacturing process. This can influence the overall cost of the medication and
potentially impact
MATERIALS, EQUIPMENTS AND METHODOLOGY

MATERIALS AND EQUIPMENTS:

● Materials
1. Ibuprofen (active ingredient)
2. Acacia mucilage 10%w/v (binder)
3. Starch 7.5%w/w (disintegrant)
4. Lactose (diluent)
5. Capsule shell (size 0)

● Equipments
1. Mortar and pestle.
2. Weighing balance
3. Sieve size
4. Hot air oven
5. Porcelain dishes
6. Measuring cylinder
7. Retort stand and clamp
8. Funnel

METHOD FOR GRANNULATION AND TABLETING

A mass of 5 g of Acacia 10%w/v weighed into a mortar and triturated. Twenty-five
millimeters (25mls) of water was measured and added bit by bit to the acacia powder
in the mortar while triturating to form a mucilage which is pourable. The mucilage
was transferred into a measuring cylinder and topped up with the remaining 25mls of
water.
PREPARATION OF GRANULES
An amount of 30g of the API and 2.25g of the disintegrant were weighed and
transferred in a clean porcelain mortar by geometric addition. The pre-prepared acacia
mucilage was added in drops and the content were transferred into the porcelain
mortar and kneaded until a agglomerates are formed. The agglomerates were passed
through sieve number 8 and placed in the oven to dry. After drying, the granules were
sieved again using a smaller aperture size sieve (16).

FLOW PROPERTIES OF GRANNULES

Carr’s and Hausner’s ratio:
20g of the prepared granules was weighed and transferred into a measuring cylinder
and the volume was recorded. The measuring cylinder containing the prepared
granules was tapped thirty times and the final volume was also recorded. From the
volumes obtained, Carr’s index and Hausner’s ratio was calculated using the
formulas:
Carr’s index = (tapped density-bulk density)/(tapped density) x 100%
Hausners’s ratio = (tapped density )/( bulk density)

Angle of Repose:
The fixed height method was employed. A retort stand and funnel was used in this
experiment. The funnel was placed at a height of 2cm above the base of the working
bench. The granule was poured through the funnel to form a coke- like shape. The
length of the base of the coke shaped granules (diameter) was measured using a ruler.
The radius was then calculated and Angle of repose was determined using the formula
below:
Tan0 = h/r, where h= height and r= radius.

Uniformity of Weight Procedure

 Weigh an empty capsule shell
 Weigh 20 randomly selected capsules(filled) together for both the machine
filling and spatula filling
 Weigh 20 randomly selected capsules individually.
 Determine the average weight.
 Calculate the % deviation for each tablet.
 Determine whether the sampled tablets passed or failed the uniformity of
weight test
RESULTS
INGREDIENTS MASTER FORMULA SCALE FACTOR(X300)
API 100mg 30g
Disintegrants 7.5mg 2.25g
Binder 3.67mg 1.1g
Diluent 68649mg 68.65g

mass
Bulk Density=
bulk volume
5g
Bulk Density=
13.5 ml
Bulk Density=0.37 g/ml
mass
Tapped Density=
true volume
5g 0.5 g
Tapped Density= =
10 ml ml

TWC=100 mg+7.5 mg+3.67 mg+ x

TWC=111.17 mg+ x
340=111.17 mg+ x
x=340 −111.17
x=228.8 mg
1 capsule=228.8 mg,

68649 mg
300 capsules=228.8 mg ×300=68649 mg= =68.65 of lactose .
1000
CALCULATION
Angle of Repose (ɵ)
Height of the cone (h) = 2cm
D1= 5.5cm
D2= 5.2 cm
D3= 5.1 cm
D1+ D 2+ D 3
D=
3
5.5+5.2+5.1
D=
3
 D 5.3
D = 5.3cm. but r= , r= , r=2.65 cm
2 2
ℎ −1 ℎ −1 2 cm 37.04
tan ∅ = , ∅ =tan =∅ =tan = ∅= =37.04 °
r r 2.65 cm 1

IV. HAUSNER RATIO

tapped density
Hausner Ratio=
bulk density
0.5 g /ml
Hausner Ratio=
0.37 g /ml
50
Hausner Ratio=
37
Hausner Ratio=1.35
' 0.5 −0.37
V. CAR R S INDEX = ×100
0.5
' 0.13
CAR R S INDEX = × 100
0.5
'
CAR R S INDEX =26 %
IBUPROFEN CAPSULES
Weight of 20 capsules = 7.35g
Average weight of 20 capsules =7.35/20=0.3675g
Weight of empty capsule = 0.08g.
Number Weight of Capsules(x) Derivation ( x − π ¿ % Derivation
of ¿
=( x − π ¿ π ×100 %
Capsules
1 0.3500 -0.0175 -4.76
2 0.3800 0.0125 3.4
3 0.3700 0.0025 0.68
4 0.3600 -0.0075 -2.04
5 0.3700 0.0025 0.68
6 0.3400 -0.0275 -7.48
7 0.3700 0.0025 0.68
8 0.3800 0.0125 3.4
9 0.3700 0.025 0.68
10 0.3800 0.0125 3.4
11 0.3700 0.025 0.68
12 0.3600 -0.0075 -2.04
13 0.3900 0.0225 6.12
14 0.3800 0.0125 3.4
15 0.3700 0.0025 0.68
16 0.3400 -0.0275 -7.48
17 0.3300 -0.0375 -10.20
18 0.3800 0.0125 3.4
19 0.3800 0.0125 3.4
20 0.3800 0.0125 3.4
π=0.3675 g
RESULTS
INGREDIENTS MASTER FORMULA SCALE FACTOR(X300)
API 100mg 30g
Disintegrants 7.5mg 2.25g
Binder 3.67mg 1.1g
Diluent 68649mg 68.65g

mass
Bulk Density=
bulk volume
5g
Bulk Density=
13.5 ml
Bulk Density=0.37 g/ml
mass
Tapped Density=
true volume
5g 0.5 g
Tapped Density= =
10 ml ml

TWC=100 mg+7.5 mg+3.67 mg+ x

TWC=111.17 mg+ x
340=111.17 mg+ x
x=340 −111.17
x=228.8 mg
1 capsule=228.8 mg,

68649 mg
300 capsules=228.8 mg ×300=68649 mg= =68.65 of lactose .
1000
CALCULATION
Angle of Repose (ɵ)
Height of the cone (h) = 2cm
D1= 5.5cm
D2= 5.2 cm
D3= 5.1 cm
D1+ D 2+ D 3
D=
3
5.5+5.2+5.1
D=
3
D 5.3
D = 5.3cm. but r= , r= , r=2.65 cm
2 2
ℎ −1 ℎ −1 2 cm 37.04
tan ∅ = , ∅ =tan =∅ =tan = ∅= =37.04 °
r r 2.65 cm 1
IV. HAUSNER RATIO
tapped density
Hausner Ratio=
bulk density
0.5 g /ml
Hausner Ratio=
0.37 g /ml
50
Hausner Ratio=
37
Hausner Ratio=1.35
' 0.5 −0.37
V. CAR R S INDEX = ×100
0.5
' 0.13
CAR R S INDEX = × 100
0.5
'
CAR R S INDEX =26 %
IBUPROFEN CAPSULES
Weight of 20 capsules = 7.35g
Average weight of 20 capsules =7.35/20=0.3675g
Weight of empty capsule = 0.08g.
Number Weight of Capsules(x) Derivation ( x − π ¿ % Derivation
of ¿
=( x − π ¿ π ×100 %
Capsules
1 0.3500 -0.0175 -4.76
2 0.3800 0.0125 3.4
3 0.3700 0.0025 0.68
4 0.3600 -0.0075 -2.04
5 0.3700 0.0025 0.68
6 0.3400 -0.0275 -7.48
7 0.3700 0.0025 0.68
8 0.3800 0.0125 3.4
9 0.3700 0.025 0.68
10 0.3800 0.0125 3.4
11 0.3700 0.025 0.68
12 0.3600 -0.0075 -2.04
13 0.3900 0.0225 6.12
14 0.3800 0.0125 3.4
15 0.3700 0.0025 0.68
16 0.3400 -0.0275 -7.48
17 0.3300 -0.0375 -10.20
18 0.3800 0.0125 3.4
19 0.3800 0.0125 3.4
20 0.3800 0.0125 3.4
π=0.3675 g

DISCUSSION
The aim of the experiment was to formulate ibuprofen capsules and also determine
the flow properties of the formulated granules. In other to form the granules the wet
granulation method was used. Granulation is the process whereby primary powder
particles are made to adhere to form larger, multiple entities called granules. The
reason for forming the granules during encapsulation was to prevent demixing of the
constituent particles and also improve the flow properties of the powder. The wet
granulation involves the massing of a mix of dry powder using a granulating fluid.
The granulating fluid used in the formulation was prepared by adding water and a
binder to form a binder solution(acacia).
The flow properties of the powder granules were determined using the fixed funnel
method to determine the angle of repose and the Hausner ratio calculated. The flow
properties have an effect on the particle size and distribution.
According to standard, Hausner ratio less than 1.25 indicates good flowability. Also, a
powder with an angle of repose between 30-40 has a pass flow.
The standard pharmacopoeia car’ s index for poor flow is 22%_35% and from the
experiment conducted the results obtained was 26% which indicates that the granules
has poor flow properties
The angle of repose obtained for the ibuprofen powder was 37.04 and the Hausner
ratio obtained for the powder was 1.35 From the results and comparing to standard,
the prepared ibuprofen has a pass flow properties and can be used for the formulation
of capsules and hausner ratio addition of glidant will improve flow of the granules
According to the British pharmacopeia, a capsule with an average weight of about
80mg more but less than 250mg and should have a percentage deviation of about 7.5
or less and not more than two (2) tablets should deviate from the stated percentage
and none should deviate by twice the stated percentage.
For hand filling capsules, it was obtained that more than two capsules (three capsules)
deviated from the stated percentage deviation. To compare the results to standard, the
hand filling capsules did not pass the test. This may be due to formulation problems in
the hand filling encapsulation such as inaccurate filling of the shells. This may lead to
inaccurate dosing when given to a patient that is either an overdose or an underdose.
For machine filling capsules, only three capsules deviated from the stated percentage
(7.5). Comparing the results to standard, the machine filling capsules failed the
uniformity of weight test.
Comparing weight uniformity of filling methods to the standard pharmacopoeia, the
uniformity of weight of ibuprofen has deviated from standard.

CONCLUSION
The granules had a bad flow properties but will improve flow properties when glidant
is added and also the uniformity of weight has failed since more two capsules is
deviated from the standard pharmacopoeia.
CHAPTER 3
SUSPENSIONS
AIM
 To appreciate the various quality control tests carried out on suspensions using
available equipment and apparatus
To operate the various equipment used in carrying out quality control tests on
suspensions
 To reconcile pharmacopoeia specifications with the practical findings and make
scientific deductions and conclusions
 To determine the sedimentation rate of calamine lotion
 To determine the sedimentation volume of calamine lotion
 To determine the flow rate of calamine lotion

OBJECTIVES
 appreciate the various quality control tests carried out on suspensions using
available equipment and apparatus

 operate the various equipment used in carrying out quality control tests on
suspensions

 econcile pharmacopoeia specifications with the practical findings and make

scientific deductions and conclusions

JUSTIFICATION

Due to the presence of the different phase systems in a suspension,which is the

continuous phase and dispersed phases there is a likelihood of instability. Hence it is
essential that quality control tests are carried out on suspensions which are meant for
the local market and public use to check if they fall within regulation specifications
and guidelines.
PROBLEM STATEMENT

All suspensions, including coarse emulsions, are inherently thermodynamically

unstable. They will, through random motion of the particles over time aggregate.
The smaller the particle size the bigger the surface area to come into contact with
body fluids. This tendency becomes increasingly important the smaller the initial
particle size and is especially significant for colloidal sized-particles. Hence attention
must be paid to any process of attrition or comminution to reduce particle size
because of the potential for creation of a population of submicron particles. The
particle size will tend to always increase with time unless some barrier is present to
keep them from coalescing or sticking when they get close to each other.

INTRODUCTION
A Pharmaceutical suspension is a disperse system in which internal phase is dispersed
uniformly as finely divided insoluble particles throughout the external phase (Brown
et al, 2000). A pharmaceutical suspension may be a coarse dispersion containing
finely divided insoluble material suspended in a liquid medium (Renna, 2008). The
external phase (suspending medium) is generally aqueous in some instance but may
be an organic or oily liquid for non-oral use. It should be physically, chemically and
microbiologically stable. The ideal properties of suspensions include
❖ The dispersed phase should have a size range of 5 to 50µm.
❖ Suspensions should have desired viscosity, so that they can be easily poured
from the container.
❖ The sediment produced in the suspensions should be easily redispersed after
shaking.
❖ Suspensions should have a pleasing odour, colour and palatability.
❖ Suspensions should be free from large or gritty particles.
❖ Suspensions meant for parenteral administration should have good
syringibility.
❖ Parenteral /ophthalmic suspensions should be sterilizable.
The advantages of suspensions include
❖ Improved chemical stability of certain drug. E.g., Procaine penicillin G
❖ Higher rate of bioavailability than other dosage forms. Bioavailability is in
following order, suspensions include
 ❖ Duration and onset of action can be controlled
❖ Suspension can mask the unpleasant/ bitter taste of drug
The disadvantages of suspension include
➢ It is bulky, therefore sufficient care must be taken during handling and
transport.
➢ It is difficult to formulate
➢ Uniform and accurate dose cannot be achieved unless
suspension is packed in unit dosage form
The quality control test carried out on suspensions include; Appearance Color, odor
and taste.
Physical characteristics such as particle size determination and microscopic
photography for crystal growth. Other tests include;
➢ Sedimentation rate
➢ Sedimentation volume
➢ Redispersibility and Centrifugation tests
➢ Rheological measurement
➢ Stress test
➢ pH
➢ Freeze-Thaw temperature cycling
➢ Compatibility with container and cap line

LITERATURE REVIEW

Pharmaceutical suspension is a liquid dosage form containing finely divided,

undissolved drug particles dispersed throughout a liquid vehicle in which the drug
exhibits a minimum degree of solubility(Koch and Ribar,2001). This dosage form is
used for providing a liquid dosage form for insoluble drugs.
The physical chemist defines the word “suspension” as two-phase system consisting
of an undissolved or immiscible material dispersed in a vehicle (solid, liquid, or
gas) (Rehm et al., 2003). Generally pharmaceutical suspensions contain aqueous
dispersion phase, however in some cases they may be an oily or organic
phase(Chatterji, 2006). The suspensions have dispersed particles above the colloidal
size i.e., mean particle diameter above 1µm (Rehm et al., 2003). Suspensions should
have good organoleptic properties; they should possess good pourability that eases the
removal of dose from container. The particle size distribution should be uniform.
They're settled solid particles should be easily redispersed on shaking. They should be
physically and chemically stable. They should be resistant against
microbial contamination (Zeigler et al, 2005). The types of suspension include,
Parenteral suspension (These are sterile suspensions that are injected into the body,
such as insulin zinc suspension), Topical suspension: (These are suspensions that are
applied to the skin or mucous membranes, such as calamine lotion), Oral suspension
(These are suspensions that are taken by mouth, such as antacids and
antibiotics) (Clark et al,2002).
sedimentation rate refers to the rate at which solid particles settle in a liquid under the
influence of gravity (Zeigler et al, (2005). When preparing suspensions or emulsions,
it is crucial to control the sedimentation rate to ensure uniform distribution of the
particles or droplets throughout the liquid. If the sedimentation rate is too high, the
particles or droplets may settle rapidly, leading to poor stability and inconsistent
dosing. On the other hand, if the sedimentation rate is too low, the particles or droplets
may remain suspended for a prolonged period, causing issues with uniformity and
ease of administration (Boyd et al,2005).
Pharmaceutical scientists and pharmacists employ various techniques to control and
measure sedimentation rates in pharmaceutical formulations. These may include the
use of suspending agents, viscosity modifiers, emulsifiers, and rheology modifiers,
which help to stabilize the system and prevent rapid settling. Techniques such as
measuring the sedimentation volume or using devices like a sedimentation balance or
zeta potential analyzer are used to assess and monitor the sedimentation behavior of
formulations (Hawkins et al, 2014).
By understanding and managing the sedimentation rate, pharmacists can optimize the
stability, uniformity, and effectiveness of suspensions and emulsions, ensuring that the
dosage form delivers the desired therapeutic effect to patients (Rose,2011).
Sedimentation volume refers to the volume of sediment that forms at the bottom of a
container after a suspension has been allowed to settle. It is a measurement used to
assess the sedimentation behavior and stability of a pharmaceutical
suspension (Eichie, F. E, 2019).

When preparing a suspension, solid particles are dispersed within a liquid vehicle.
Over time, due to the effect of gravity, the particles may settle and form a sediment
 at the bottom of the container. The sedimentation volume is the volume occupied
by this settled sediment (Cook and Moore, 2019).

classification of suspensions
•1) Routes of administration
•2) According to nature of dispersed phase and methods of preparation
•3) According to nature of sediment
•4) Based On Proportion Of Solid Particles ( Dilute suspension2 to10%w/v
solid).Conc. suspension (50%w/v solid)
•5)Based On Size Of Solid Particles
Colloidal susp(< 1 micron)
Coarse suspension (>1 micron)
Nano suspension (10 ng)

Desirable Properties of suspension

1)Suspensions should possess good pourability hence ease of dosing from
container.
2)They should have good organoleptic properties.
3)It must remain sufficiently homogenous for at least the period between
shaking the container and removing the dose.
4)There should be ease of redispersion of settled solid particles.
5) They should be physically and chemically stable.
6) They should be resistant to microbial contamination.
7) Particle size and distribution should be small and uniform. (elegant, gritty-free).
8) Must exhibit thixotropy.

Routes of administration of suspension

Suspensions can be administered by:
➢Oral
➢Topical
➢Parenteral routes
Oral suspensions
• must contain suitable flavoring and sweetening agents.
•can be suitable formulations for drugs with unpleasant taste in solution dosage
form like paracetamol, chloramphenicol palmitate.

2) Topical suspensions
•These suspensions are meant for external application and therefore

•should be free from gritty particles.

• e.g calamine lotion.

3) Parenteral suspensions
•These suspensions should be sterile.
•Should possess property of syringability.
•Example: Vaccines are formulated as dispersions of killed microorganisms
for example in Cholera vaccine
Or
• as toxoid adsorbed on to substrate like aluminium hydroxide or phosphate
for prolonged antigenic stimulus. For example adsorbed Diphtheria and
Tetanus toxoid

•2. According to nature of dispersed phase and methods of preparation

•The suspensions are classified as suspensions containing diffusible solids,
indiffusible solids, poorly wettable solids, precipitate forming liquids and
products of chemical reactions.

Types of insoluble solids:

1) DIFFUSIBLE SOLIDS
There are two types of insoluble solids which constitute the internal or
dispersed phase. These are
 1. Consist of solids insoluble in water but easily wettable

2. On shaking with water, solid particles diffuse readily through out the
liquid and remain suspended for a long time to enable satisfactory dose
removal after redispersion.
2) INDIFFUSIBLE SOLIDS-
➢ eg. sulphadimidine and chalk.
➢These sediment too rapidly and require the addition of other materials to
reduce sedimentation rate to an acceptable level

According to nature of sediment

 Flocculated
 Deflocculated

FLOCCULATION
a condition which occurs as a result of the lowering of electrical forces of repulsion.
Flocculation is a dispersed system, so that the force of attraction predominate.
➢Particles can approach each other more closely and form aggregates

Flocculated Suspensions:
•The dispersed phase solid particles aggregate leading to network-like structure of
s.p in dispersion medium.
•The aggregates form no hard cake.
•These aggregates settle rapidly due to their size (high sedimentation rate)
• Sediment formed is loose and easily redispersible.
•Non elegant, as dispersed phase tends to separate out from the dispersion
medium

Flocculated suspension contains the most stable pharmaceutical agents

Examples of flocculating agents

1. natural electrolytes such as NaCl, KCl
2. Surfactants
3. polymeric flocculating agents such as citrate, phosphate salt, sulfate
Deflocculation suspension
1. In this, the electrical repulsive forces between particles exceeds the
attractive forces, the particles are kept as separate/discrete entities.
2. The repulsive forces btwn particles allow them to slip past each other as
they sediment.
In deflocculated suspension, smaller particles settle slowly and therefore remaining
supernatant liquid appears

Deflocculated Suspensions
•The solid particles exist as separate entities in dispersion medium.
•The solid drug particles settle slowly as rate of sedimentation is low.
•The sediments form hard cake.
•As sediments are formed eventually there is difficulty of redispersion.
•The suspension is more elegant as dispersed phase remain suspended for a
long time giving uniform appearance

SUSPENDING AGENTS
Suspending agents are substances that are used to:
➢keep finely divided insoluble materials suspended in a liquid media by
preventing their agglomeration (coming together)
➢impart viscosity to the dispersion media so that the particles settle more
slowly

Types of suspending agents

Natural agents such as
1. animal sources: gelatin
2. plant sources: acacia, tragacanth, starch and alginate
3. Mineral sources: kaolin , bentonite, clay

SEMI-SYNTHETIC AGENTS
Consist of substituted cellulose such as
1.hydroxyethylcellulose
2.methyl cellulose
3. sodium carboxymethylcellulose

Synthetic agent
 carboxypolymethelene
 colloidal silicon dioxide

MATERIALS AND EQUIPMENTS

 Mortar and pestle
 Measuring cylinder
 Magnesium trisilicate
 Light magnesium carbonate
 Sodium carbonate
 Concentrated peppermint
 Chloroform
 Water
 Pipette
 Calamine
 Zinc oxide
 Bentonite
 Sodium citrate
 Liquid phenol
 Chloroform
 Weighing balance

METHODOLOGY
PREPARATION OF CALAMINE LOTION
An amount of 15.75g of calamine,5.25g of zinc oxide, 3.15g of bentonite and
0.525g of sodium citrate was weighed into a mortar and triturated to reduce
particle size and mix. A volume of 5.25ml of chloroform was measured and
 added to the mixture. It was then transferred to a tarred 100ml container. About
0.525ml of liquid phenol was added and it was topped up to the 100ml mark and
labelled appropriately.

DETERMINATION OF SEDIMENTATION RATE

The calamine login was shaken well then poured into a beaker from the mortar
after rising it with water (100ml) and about 50ml of the suspension was poured
into a measuring cylinder and made to stand for an hour. The volume of
sediment is recorded every ten minutes for an hour.
PLATE 1

DETERMINATION OF SEDIMENTATION VOLUME

About 50ml of the suspension was poured into a measuring cylinder and made
to stand for 24 hours. The volume of sediment was taken after twenty -four
hours.

DETERMINATION OF FLOW RATE

 In other to determine the flow rate, about 25ml of the suspension was pipetted and
made to flow freely from the pipette. The time taken for all the suspension to flow
out of the pipette was recorded.

RESULTS AND CALCULATIONS

SEDIMENTATION RATE TABLE
Times(minutes) Volume of Sediment(A) Volume of Sediment(B)
0 50ml 50ml
10 50ml 49.5ml
20 49ml 48.5ml
30 48.5ml 48ml
40 47.5ml 47ml
50 47ml 46.5ml
60 46.5ml 46ml

SEDIMENTATION VOLUME
Sedimentation Volume = ultimate volume of sediment after 24hrs
Initial volume of sediment
For sample A(prepared)
Volume of sediment after 24hrs=43ml
Initial volume of sediments=50ml
Sedimentation volume = 43ml/50ml
SV=0.86
The sedimentation volume of the prepared calamine lotion is 0.86
For sample B(Market)
Volume of sediment after 24hrs = 28ml
Initial volume of sediment = 50ml
Sedimentation volume = 28ml/50ml
= 0.56
The sedimentation volume of the market calamine lotion is 0.56.

A GRAPH OF VOLUME OF SEDIMENT(A) AGAINST TIME

 51

50

49
volume of sediment

48 Series2
Linear (Series2)
47 Series4
Linear (Series4)
46 Series6
Linear (Series6)
45

44
0 10 20 30 40 50 60 70
Time

Slope = -0.06071
A GRAPH OF VOLUME OF SEDIMENT(B) AGAINST TIME

f(x) = NaN x + NaN

12

10

8
Series1
Linear (Series1)
6 Series2
Series3
Series4
4
Series5

0
0 2 4 6 8 10 12

Slope = 8.2456

APPARENT VISCOSITY
SAMPLE A (Product Prepared)
Determinations 1st Reading(s) 2nd Reading(s) Average(s)
Det 1 21.10 21.30 21.20
Det 2 20.00 19.95 20.00
Det 3 21.10 20.00 20.60

SAMPLE B(Market)
Determination 1st Reading(s) 2nd Reading(s) Average(s)
Det 1 17.00 16.78 16.915
Det 2 15.50 16.00 15.775
Det 3 16.00 15.80 15.925

CALCUTATION OF AVERAGES
SAMPLE A
Total Average = 21.2+20.0+20.60
3
Total Average = 20.60s
SAMPLE B
Total Average = 16.915+15.775+15.925
3
=16.20s
APPARENT VISCOSITY CALCULATIONS
Apparent Viscosity(sample A)= volume of pipette(ml)
Time taken(s)
= 18ml/20.6s
= 0.87ml/s
Apparent Viscosity (Sample B) = 18ml/16.2s
= 1.11ml/s
Therefore the apparent viscosities of sample A and B are 0.87ml/s and 1.11ml/s
respectively.

DISCUSSION
DISCUSSION
sedimentation rate for a pharmaceutical suspension involves monitoring the rate at
which solid particles settle in the suspension over a specific period of
time. The sedimentation volume refers to the volume occupied by the settled particles
or droplets at the bottom of a container after a suspension has been allowed to
settle. The importance of determining the sedimentation rate and sedimentation
volume is because sedimentation rate provides information about the settling behavior
of solid particles or droplets in a suspension over time. By measuring the
sedimentation rate and volume, it is possible to evaluate the stability of the
suspension. A high sedimentation rate indicates rapid settling, which may lead to
issues such as poor redispersibility, inconsistent dosing, and non-uniformity of the
drug distribution. On the other hand, a low sedimentation rate suggests better stability,
with particles or droplets remaining suspended for a longer duration. Also, it helps in
formulation optimization, that is determination of the sedimentation rate allows
formulation scientists and pharmacists to optimize the suspension formulation. By
adjusting parameters such as the concentration of suspending agents, viscosity
modifiers, or rheology modifiers, they can control the sedimentation rate and improve
the stability of the suspension. The goal is to develop a formulation that minimizes
particle settling while maintaining a homogeneous and stable system. The flow rate of
a suspension refers to the rate at which the suspension flows or moves through a given
system or apparatus. It is affected by the viscosity of the suspension.
In the quality control of suspensions, it was determined that the sedimentation volume
of the prepared calamine lotion was 0.86 and the one on the market was 0.56.
Comparing the calamine lotion prepared in the lab to the one on the market, the
prepared calamine lotion has higher sedimentation volume. This may due to higher
viscosity of the prepared lotion than the one on the market.According to standard
literature, sedimentation volume should not be less than 0.2 .Since the sedimentation
volume of both suspensions obtained is above 0.2, the particles can remain suspended
in the suspension for a dose to be taken . Hence both suspensions can be classified as
an ideal suspension.
The flow rate of the prepared calamine lotion was 0.874mls/s and that of the standard
was 1.111ml/s. The calamine lotion on the market had a higher flow rate than the
prepared one due to the fact that the suspension was less viscous. Hence it flowed
easily in a short period of time. According to literature, flow rate should not be greater
than 1.0 Per the values obtained, both suspensions passed the test as the values were
less than 1.0.
According to the graph the sedimentation rate of the prepared calamine lotion was
0.0607ml/s and that the one on the market was 8.2458ml/s. Lower sedimentation rate
indicates that the particles in a suspension sedimented slowly whiles a high
sedimentation rate indicates that the particles sediments easily. This indicates that the
prepared calamine lotion sediments slowly whiles the one on the market sedimented
quickly.

CONCLUSION
From the above results, it can be concluded that the prepared calamine lotion and the
market calamine lotion were within standard specification. Therefore the quality of
the two suspensions have been evaluated successfully.

RECOMMENDATION
Quality control for suspensions may all have limitation and only one will not ensure
an ideal suspension, hence many test should be carried out on the same formulation.
Other test includes particle size, rheology appearance and texture.
Scientific machines should be develop to aid in rapid and instant determination of
flow rates, sedimentation rate and sedimentation volume of suspensions to minimize
or prevent the probability of human errors during experiment and also to save time.

CHAPTER 4
QUALITY CONTROL ON TABLETS
EXPERIMENT FOUR(4)
QUALITY CONTROL
CHAPTER FOUR(4)

AIM:

 The aim of this study is to enhance the quality control test conducted on solid
pharmaceutical dosage forms to ensure the safety, efficacy and compliance of this
formulatons.
To carry out uniformity of weight test on letmol paracetamol and eskal
paracetamol
  To carry out disintegration tests on letmol paracetamol and eskal paracetamol
 To carry out dissolution test on letmol paracetamol and eskal paracetamol
 To carry out friability test on letmol paracetamol and eskal paracetamol

SPECIFIC OBJECTIVES
accurately calculate the amount of ingredients needed for preparing paracetamol
tablets of the brand Letamol and Eskay.
 appreciate the various methods of granulation.
 determine the flow properties of granules.
 appreciate the importance of particle size analysis in pharmacy.
 appreciate the graphical presentation of the size distribution of particles.
 appreciate pre-compression factors and post compression factors which can affect
the quality of the paracetamol tablets.

PROBLEM STATEMENT
In order to ensure that the products satisfy the necessary criteria for safety, efficacy,
and quality, solid dosage form quality control is a crucial component of
pharmaceutical manufacturing. But various difficulties and problems can appear
throughout the quality control procedure, affecting the dependability and consistency
of solid dosage forms. Some of the challenges and issues with solid dosage form
quality control are highlighted in this problem statement:
 Variability in content uniformity: Achieving consistent content uniformity across a
batch of solid dosage forms can be challenging. Variations in formulation,
manufacturing processes, and raw materials can lead to uneven distribution of active
ingredients, resulting in inconsistent dosing and potential efficacy concerns.
 Inadequate dissolution profiles: Dissolution testing is crucial to assess the drug release
characteristics and bioavailability of solid dosage forms. However, inconsistencies in
dissolution profiles can occur due to variations in formulation, manufacturing
 processes, or equipment used. Inaccurate dissolution results can impact product
performance and efficacy.
 Lack of robust analytical methods: Analytical methods used for quality control testing
may lack accuracy, precision, or sensitivity, leading to unreliable results. Inadequate
methods can compromise the detection and quantification of impurities, degradation
products, or active ingredients, affecting the overall quality assessment of solid
dosage forms.
 Insufficient stability testing: Stability testing is essential to evaluate the shelf life and
storage conditions of solid dosage forms. However, inadequate or incomplete stability
testing protocols may fail to identify potential degradation, changes in physical
properties, or loss of potency over time, resulting in compromised product quality and
efficacy.
 Packaging integrity issues: The packaging system for solid dosage forms plays a vital
role in protecting the product from environmental factors, moisture, and tampering.
However, inadequate packaging design or flaws in packaging materials can lead to
issues such as moisture ingress, product degradation, or compromised product
integrity.

JUSTIFICATION
Patient Safety: Quality control tests are essential to ensure the safety of patients
consuming solid pharmaceutical dosage forms. These tests detect and prevent the
presence of impurities, contaminants, or incorrect levels of active ingredients,
minimizing the risk of adverse effects or ineffective treatments. By conducting
rigorous quality control tests, manufacturers can identify and mitigate potential risks,
ensuring the medications meet the required safety standards.
Efficacy and Therapeutic Effectiveness: Quality control tests verify the potency and
uniformity of solid dosage forms. Accurate drug content and dissolution tests ensure
that each dosage unit contains the appropriate amount of active ingredient and
releases it effectively. Consistent quality control measures contribute to the reliability
and predictability of medication response, enhancing the therapeutic effectiveness and
ensuring desired clinical outcomes.
Regulatory Compliance: Regulatory agencies mandate quality control tests as part of
the approval process for pharmaceutical products. Compliance with these regulations
is crucial for manufacturers to obtain market authorization and demonstrate the safety
and efficacy of their medications. Quality control tests provide the necessary data and
evidence to support regulatory submissions and ensure adherence to Good
Manufacturing Practices (GMP) and other industry standards.

INTRODUCTION

Solid dosage forms are pharmaceutical formulations that areadministered in a

solid state, typically in the form of tablets, capsules, powders, or granules. They are w
idely used in the pharmaceutical industry due to their convenience, stability,
and ease of administration. Solid dosage forms offer precise
dosing, better patient compliance, and improved shelf life
compared to other dosage forms.
Quality control of solid dosage forms involves a comprehensive set of processes and t
ests to ensure the safety, efficacy, and quality of pharmaceutical products in
solid form, such as tablets, capsules, powders, and granules. Solid dosage
forms are widely used due to their convenience, stability, and ease of administration.
Here is an introduction to the key
aspects and methods involved in the quality control of solid dosage forms:
Physical appearance: Visual inspection is performed to ensure
that the solid dosage form meets the required appearance criteria.
This includes assessing characteristics such as color, shape, size, and surface texture.
Any abnormalities, such as discoloration, chipping, or cracking, are noted.
Weight variation: Weight variation testing ensures that individual
solid dosage units within a batch are within the specified weight range.
This is important to ensure consistent
dosing and to avoid potential under- or overdosing. A representative sample is taken,
and the weights of the units are-measured and compared.
Hardness and friability: Hardness testing determines the
resistance of tablets or capsules to breakage or crumbling
under compression forces. Friability testing measures the
tendency of tablets to undergo abrasion or erosion during handling.
These tests help assess the mechanical strength and durability of the solid dosage for
m.
Disintegration and dissolution: Disintegration testing evaluates the time it takes for a
solid dosage form to break down into smaller particles when exposed to a specified
medium. Dissolution testing measures the rate and extent to
which the active ingredient(s) dissolve from the dosage form.
These tests assess the drug release characteristics and bioavailability of the product.
Assay of active ingredients: The concentration or potency of the active ingredient(s)
in the solid dosage form is determined through an assay. Analytical techniques like
high-performance liquid chromatography (HPLC),
UV spectrophotometry, or titration methods are commonly used.
This ensures that the dosage form contains the specified
amount of active ingredient(s) for therapeutic efficacy.
Uniformity of content: Content uniformity testing verifies that the
active ingredient(s) are uniformly distributed throughout-the solid dosage form.
This is essential to ensure consistent dosing and efficacy.
Samples are taken from different locations within a batch,
and their content is analyzed to verify uniformity.
Dissolution profile: Dissolution profiling assesses the drug release pattern of a
solid dosage form over a specified time. This is particularly important for controlled-
release formulations, where the drug release needs to be sustained
over an extended period. Dissolution profiles are compared
against reference standards or predetermined specifications.
Stability testing: Stability studies are conducted to evaluate
the shelf life and storage conditions of the solid dosage form.
Samples are subjected to accelerated and long-term stability
testing to monitor physical, chemical, and microbiological changes over time.
This helps ensure product quality and performance throughout its intended shelf life.
Packaging integrity: The packaging system for solid dosage
forms, including blister packs, bottles, or strip packs, is assessed ed for its integrity.
This involves evaluating factors such as moisture resistance, light protection,
and the ability to maintain product integrity during storage and transport.
Compliance with regulatory standards: Quality control of
solid dosage forms involves adhering to applicable regulatory
standards and guidelines set by regulatory authorities like theFDA,
EMA, or other regional health authorities.
Compliance with these standards ensures the safety, efficacy, and quality of
the product.
These are some of the key aspects involved in the quality
control of solid dosage forms.
The specific tests and procedures may vary depending on the type of solid dosage
form, formulation complexity, and regulatory requirements in different regions.
The goal is to ensure that each solid dosage
unit consistently meets the required specifications, providing
patients with safe and effective medications.

LITERATURE REVIEW
Challenges in Quality Control of Solid Dosage Forms
This
review article discusses the challenges encountered in quality control of solid dosage f
orms. It covers various
aspects, including content uniformity, dissolution testing, stability studies,
and analytical methods. The authors
highlight the factors contributing to variability in quality
control results and propose strategies to overcome these challenges
such as improved formulation design, robust testing protocols,
and enhanced analytical techniques. [Smith, J., Johnson, A., Brown, C.
2018]. Content Uniformity of Solid Dosage Forms: A Critical Review"
This review focuses on content uniformity, a critical parameter in
solid dosage form quality control. The authors
discuss the causes of content uniformity issues, such as
formulation variability, manufacturing processes,
and analytical methods. They explore the impact of content
uniformity on drug efficacy and patient safety and present
recommendations for improving content uniformity testing
methods and strategies. [Patel, K., Gupta, M., Mehta, T.
2017]. Dissolution Testing for Solid Oral Dosage Forms
This
review provides an overview of dissolution testing in quality control of solid dosage f
orms. It discusses the importance of dissolution testing in assessing drug release
and bioavailability. The authors review various dissolution testing methods, apparatus,
and regulatory guidelines. They also address challenges associated with dissolution te
sting, such as method development and validation, and propose strategies
for enhancing dissolution testing protocols. [Sharma, N., Jain, S., Jain, R. 2019]
Stability Testing of Solid Dosage Forms:
This comprehensive review focuses on stability testing of
solid dosage forms. It covers various aspects of stability testing
testing, including accelerated stability testing, long-term stability studies, stability-
indicating methods, and degradation mechanisms.
The authors discuss the regulatory requirements for
ntsfor stability testing and provide insights into the challenges
and considerations in conducting stability studies for solid dosage forms. [Lee, S.,
Lee, W., Kim, M. 2020] Analytical Methods for Quality Control of Solid Dosage
Forms
This review article discusses the analytical methods employe-
din the quality control of solid dosage forms. It provides an overview of various techn
iques, including spectroscopic-methods (UV, IR,
NMR), chromatographic methods (HPLC, GC), and dissolution testing.
The authors highlight the
advantages and limitations of each technique, discuss method
development and validation, and emphasize the importance of
selecting appropriate analytical methods for accurate quality assessment. [Gupta, R.,
Sharma, N., Jain, R. 2016]

Quality control tests

Tablets Capsules
1. Uniformity of weight 1. Uniformity of Weight
 2. Friability 2. Disintegration
3. Hardness 3. Dissolution
4. Dissolution 4. Assay
5. Assay
6. Uniformity of Dimension
7. Disintegration

WEIGHT UNIFORMITY TEST

Test done to ensure that there is little or no variation in weight among tablets in a
batch and that every tablet contains the right amount of active ingredients. Due to
increased awareness of physiological availability, the weight uniformity test has been
included in the monographs of all tablets and all capsules intended for oral
administration where the range of the size of the dosage form available includes 50mg
or smaller sizes. Tablet monographs with a weight uniformity requirement do not
have weight variation requirements.
Furthermore, uniformity of weight of tablets and capsules indicates the quality control
of specific batch of tablets and capsules. Uneven distribution may alter the dose in
each individual drug and therefore causes a lot of problems such as unable to reach
the therapeutic range or exceed the therapeutic and reach toxic range.
By the USP method, 10 dosage units are individually assayed
for their content according to the assay method described in the individual monograph
.
The requirements for content uniformity are met if the amount
of active ingredient in each dosage unit lies within the range
of 85% to 115% of the label claim and the relative standard
deviation is less than 6.0%.

UNITED STATES PHARMACOPOEIA (USP)

Average Weight Percentage(%) difference

130 mg or less 10
More than 130mg but less that 324 mg 7.5
More than 324 mg 5

BRITISH PHARMACOPOEIA (BP)

average weight Percentage(%) difference

80 mg or less 10
More than 80mg but less that 250 mg 7.5
More than 250mg 5

DISINTEGRATION TEST

This test determines whether dosage forms such as disintegrate within a prescribed
time (disintegration time) when placed in a liquid medium under the prescribed
experimental conditions. Disintegration is defined as that state in which no residue of
the unit under test remains,or if a residue remains,it consists fragments of
disintegrated parts of tablets component parts such as insoluble coating of the tablets.
The disintegration provides drug particles with an increase surface area within the
gastrointestinal tract and is the first important step toward solution, so this test is
important to ensure the disintegration and discharge the drugs to the body fluids for
dissolution. It is the test used to measure the time of tablets disintegrating.

Except for chewable tablets, this test is used as a control for

oral tablet formulations. According to the British and
US Pharmacopeia, uncoated tablets must dissolve in water with a temperature of 37
°C within 15 minutes. Additional tests that are outlined in both the USP
and the British pharmacopeia
must be carried out if one or more tablets fail to dissolve.
The enteric coated tablet is the only one that is not submerged in water for the disinteg
ration test. It undergoes an hour-long test in
a simulated gastric fluid environment, during which time it
cannot show any signs of disintegration, cracking, or softening.

USP. method for uncoated tablets

Disintegration test on 6 tablets. If 1 or 2 tablets
from the 6 tablets fail disintegrate completely
within 30min repeat the same test on another 12
tablet. (i.e. the whole test will consume 18 tablets).
NLT 16 tablets disintegrate completely within the
time. If more than two tablets (from the 18) fail to
disintegrate, the batch must be rejected.

UNIFORMITY OF DIMENSION TEST

The diameter and the thickness of a tablet is measured. Tablet thickness is determined
by the diameter of the tablet. Micrometer and vernier caliper are used for checking
tablets thickness. Thickness and diameter should be controlled within +_5% variation
of a standard valve. Thickness must be controlled for consumer acceptance of the
product, and to facilitate packaging.
The physical dimensions of the tablet along with the density of the materials in the
tablet formulation and their proportions, determine the weight of tablet.

DISSOLUTION TEST
Dissolution is a test used by the pharmaceutical industry to characterize the
dissolution properties of the active drug, the active drug release and the dissolution
from a dosage formulation . Dissolution testing is used to formulate the drug dosage
form and to develop quality control specifications for its manufacturing process. An
in-vitro dissolution test is a critical test that has to correlate with in-Vito clinical
studies and which could require specific method developments.
Dissolution testing is described in many pharmacopoeia, in EP, USP, and FDA
guidelines. Dissolution test or studies are conducted to show that the release of the
drug from the tablet 100%.

Dissolution test is based on four processes

1. Wetting
2. Solubility
3. swelling
4. Diffusion
Particle size, shape, surface area is important factor
can affect the rate of dissolution of drug. The
aqueous solubility is increases, increases rate of
dissolution drug. Dissolution Basket method)
Tablet was placed in a small wire mesh basket
attached to the bottom of the shaft connected to a
variable speed motor. The basket is deep in a
dissolution medium (as specified in monograph)
contained in a 1000 ml flask. The flask is
cylindrical with a hemispherical bottom. Constant
temperature bath of flask maintained at 37 ± 0.5oC.
The speed of motor is adjusted to turn at the
specified and quantity sample withdrawn at
intervals at specific interval for determination of
concentration of drug (Figure No.5).
USP Dissolution apparatus II (Paddle method)
It is same as apparatus-1, except the basket is
replaced by a paddle. The dosage form is allowed to
sink to the bottom of the flask before stirring. For
dissolution test U.S.P. specifies the dissolution test
medium and volume, type of apparatus to be used,
rpm of the shaft, time limit of the test and assay
procedure for. The test tolerance is expressed as a
% of the labeled amount of drug dissolved in the
time limit (Figure No.6).
Dissolution testing and interpretatule into solution
through semi permeable membrane.
Semi permeable membrane
Thin layer that can separate two phases.
Steady sate
Mass transfer process is remains constant per unit
time.
Osmotic pressure
The pressure is exerted in walls of semi permeable
membrane through concentration gradient.
Diffusant (penetrant)
The amount of material transport in semi permeable
membrane.
Con. Gradient
Concentration of material transport in region of
high con. To region of low con.
Mechanism of Dissolution
Dissolution mechanism based on two concept one is
a mass transfer process. Second is the concentration
of receptor compartment is maintain lower level as
compared to donor compartment is known as sink
condition.
Theories of Drug Dissolution
Dissolution concept mainly deepens on three
dissolution theories, such as, Diffusion layer
model/Film Theory, Danckwert’s
model/Penetration or surface renewal Theory and
Interfacial barrier model/Double barrier or Limited
solvation theory.
Factor Affecting Dissolution
Dissolution rate of drug is mainly affected by
various factors such as, Physicochemical Properties
of Drug, Drug Product Formulation Factors,
Processing Factors, Factors Relating Dissolution
Apparatus and Factors Relating Dissolution Test
Parameters.
Dissolution test apparatus
IP apparatus
First is Paddle apparatus (IP) and second is Basket
apparatus (IP).
USP apparatus
Apparatus 1 (rotating basket), Apparatus 2 (paddle
assembly), Apparatus 3 (reciprocating cylinder),
Apparatus 4 (flow-through cell), Apparatus 5
(paddle over disk), Apparatus 6 (cylinder) and
Apparatus 7 (reciprocating holder)

USP dissolution apparatus 1 (Basket method)

Tablet was placed in a small wire mesh basket
attached to the bottom of the shaft connected to a
variable speed motor. The basket is deep in a
dissolution medium (as specified in monograph)
contained in a 1000 ml flask. The flask is
cylindrical with a hemispherical bottom. Constant
temperature bath of flask maintained at 37 ± 0.5oC.
The speed of motor is adjusted to turn at the
specified and quantity sample withdrawn at
intervals at specific interval for determination of
concentration of drug (Figure No.5).
USP Dissolution apparatus II (Paddle method)
It is same as apparatus-1, except the basket is
replaced by a paddle. The dosage form is allowed to
sink to the bottom of the flask before stirring. For
dissolution test U.S.P. specifies the dissolution test
medium and volume, type of apparatus to be used,
rpm of the shaft, time limit of the test and assay
procedure for. The test tolerance is expressed as a
% of the labeled amount of drug dissolved in the
time limit (Figure No.6).
Dissolution testing and interpretation
This test, according to both the British and the USP, uses the USP
Apparatus I to assess the amount of time needed for a specific proportion of the drug
ingredient to dissolve under a specific set of circumstances. This test is carried out to
assess the drug's physiological availability. The temperature must be 37℃, and the
paddle speed must be 100 spins per The USP states that the capsule should be able to
pass the test if 85% of the medicine was able to dissolve within 30 minutes, however
the BP states that the capsule should pass the test if 75% of the indicated amount of
drug dissolves within 45 minutes.

FRIABILITY TEST

Friability testing is a laboratory technique used by pharmaceutical industry to test the

durability of tablets during transit . This testing involves repeatedly dropping a sample
of tablets over a fixed time, using a rotating wheel with a baffle. According to the
USP, the allowed limit of friability is not more than 1.0% of weight loss. friability of
uncoated tablets is the phenomenon where by tablet surface are damaged and/or show
evidence of lamination or breakage when subjected to mechanical shock or attrition
and expressed as the loss of mass and it is calculated as a percentage of the initial
mass. The friability test is intended to evaluate the physical strength of the tablet or
the ability of the tablets to withstand abrasion during packaging, handling and
shipping.

To determine the tablet strength, this test is conducted. The friabilator is a tool
used to assist in determining this. Approximately 10 tablets are chosen, and 10 tablets
are weighed. The tablets are placed in the friabilator, which spins them for 4 minutes,
or 100 revolutions, in accordance with the calculated time. The tablets are reweighed
and dusted after the revolution. Then, any weight loss is taken into consideration. No
more than 1% of the body weight should be lost.

THE HARDNESS TEST

Hardness of the tablets is an important parameter because pharmaceutical tablets must
have sufficient ability to survive the handling forces during packaging and breaking
down the tablets, it is the test used to measure the solidity of tablet to stand post
operation procedure such as packing, storage or handling. Although there is no
official test for tablets hardness, this property must be controlled during production to
ensure that the products is firm enough to withstand handling during packaging and
transporting without breaking, chipping or crumbling. Hardness may affect friability
and disintegration time.it usually affects drug dissolution and release, and it may
affect bioavailability.

Factors Affecting the Hardness

1. Compression of the tablet and compressive
force.
2. Amount of binder. (More binder à more
hardness)
3. Method of granulation in preparing the
tablet (wet method gives more hardness than
direct method, Slugging method gives the
best hardness).

Tablet Thickness
In accordance to standard, tablet thickness should be within a ±5% variation. For the
product to be accepted by consumers, any thickness difference within a given lot of
tablets or between manufacturer's lots should not be visible to the unassisted eye. The
percentage variation must be calculated to ensure uniform thickness and aid in
speeding up the packaging process.

MATERIALS

 Weighing balance
 Vernier caliper
 Disintegration apparatus
 USP dissolution apparatus II
 Friabilator
 Letmol paracetamol
 Eskal paracetamol
METHODOLOGIES

UNIFORMITY OF WEIGHT TEST

A total number of twenty tablets each of letmol paracetamol tablets and eskal
paracetamol tablets were weighed separately together to attain the total weight of both
letmol and eskal paracetamol tablets The average weight was calculated. The letmol
paracetamol and eskal paracetamol tablets were weighed individually and the
variation of the individual weights from the average weight were calculated in
percentage. The percentage deviations obtained were compared to the standard (BP),
which states not more than two tablets should deviate from the stated percentage and
none should deviate by twice the stated percentage.
DISINTEGRATION TEST
This experiment was performed using the British pharmacopoeia standard. Six tablets
each of letmol paracetamol and eskal paracetamol were used, each tablets ets was
placed in each hole of the basket rack and suspended in a beaker containing 800ml of
water (used as medium) at a temperature of 37℃ for 15 minutes for uncoated tablets.
The time taken for the tablet to completely break down was recorded.
Disintegration Test Machine

Plate 1.
FRIABILITY TEST
A total of about ten tablets each of letmol paracetamol tablets and eskal paracetamol
were selected and weighed. The tablets were put in the friabilator for four minutes
(100 revolutions). The tablets were dedusted and reweighed. Any loss in weight was
determined.
FRIABILATOR
Plate 2
DISSOLUTION TEST
One tablet each of letmol paracetamol and eskal paracetamol was placed in the
dissolution tester machine at a given set of conditions. Temperature at 37 ℃, speed at
50rpm, for 30minutes.5ml of the solution was measured and filtered, the filtrate was
used to determine the absorbance and transmittance using a calorimeter. The time
taken for the tablet to completely dissolve was recorded and the percentage of the
drug dissolved was calculated.
USP APPARATUS II
PLATE 3
UNIFORMITY OF DIMENSIONS
To check the uniformity of the dimensions, a vinier caliper was used to measure the
thickness and diameter of three randomly picked tablets of both letmol paracetamol
and eskal paracetamol. The values were recorded.
VERNIER CALIPER
PLATE 4
RESULTS AND CALCULATION
WEIGHT UNIFORMITY TEST ON DIFFERENT BRANDS OF PARACETAMOL
LETAMOL TABLETS
Weight of 20 tablets = 12.22g
Average weight = 12.22/20
AV = 0.6110g
Number of tablets Weight g (x) Deviations(x- %Deviations
mean)
1 0.62 0.009 1.47
2 0.60 -0.011 -1.80
3 0.60 -0.011 -1.80
4 0.60 -0.011 -1.80
5 0.62 0.009 1.47
6 0.60 -0.011 -1.80
7 0.60 -0.011 -1.80
8 0.62 0.009 1.47
9 0.62 0.009 1.47
10 0.61 -0.001 -0.16
11 0.60 -0.011 -1.80
12 0.62 0.009 1.47
13` 0.62 0.009 1.47
14 0.61 -0.001 -0.16
15 0.63 0.019 3.11
16 0.61 -0.001 -0.16
17 0.61 -0.001 -0.16
18 0.61 -0.001 -0.16
19 0.62 0.009 1.11
20 0.60 -0.011 -1.80
ESKAY TABLETS
Weight of the 20 tablets = 11.47g
Average weight = 11.47/20
AV=0.5735g
Number of tablets Weight (x) Deviations (x- %Deviations
mean)
1 0.58 0.0065 1.13
2 0.55 -0.0235 -4.09
3 0.57 -0.0035 -0.61
4 0.56 -0.0135 -2.35
5 0.58 0.0065 1.13
6 0.57 -0.0035 -0.61
7 0.59 0.0165 2.87
8 0.58 0.0065 1.13
9 0.57 -0.0035 -0.61
10 0.57 -0.0035 -0.61
11 0.58 0.0065 1.13
12 0.57 -0.0035 -0.61
13 0.59 0.0165 2.87
14 0.57 -0.0035 -0.61
15 0.58 0.0065 1.13
16 0.59 0.0165 2.87
17 0.58 0.0065 1.13
18 0.57 -0.0035 -0.61
19 0.55 -0.0235 -4.09
20 0.57 -0.0035 -0.61

FRIABILITY TEST
ESKAY
Initial weight = 6.92g
Final weight = 6.87g
%friabilty = initial weight - final weight x 100
Initial weight
%friability = 6.92g-6.87g x 100
 6.92g
= 0.72%
LETAMOL TABLETS
Initial weight = 6.78g
Final weight = 6.70g
%friability = 6.78g-6.70g x 100
6.78g
= 1.18%
UNIFORMITY OF DIMENSION
ESKAY TABLETS
Number of tablets Diameter(cm) Diviation %Deviation
1 1.30 0 0
2 1.30 0 0
3 1.30 0 0
4 1.30 0 0
5 1.30 0 0
6 1.30 0 0

Mean diameter = 1.3x6

6
=1.30cm
LETAMOL TABLETS
Number of tablets Diameter(cm) Deviation %Deviation
1 1.20 -0.02 -1.64
2 1.25 0.03 2.46
3 1.20 -0.02 -1.64
4 1.25 0.03 2.64
5 1.20 -0.02 -1.64
6 1.20 -0.02 -1.64
Mean 1.22cm

THICKNESS OF TABLETS
ESKAY LETAMOL
0.4 0.4
0.4 0.4
0.4 0.45
0.4 0.45
0.4 0.45
0.4 0.45

DISINTEGRATION TEST
ESKAY TABLETS
The time needed to finish the disappearance of paracetamol (eskay)500mg tablet was
3 minutes at 37℃.
LETAMOL TABLETS
The time needed to finish the disappearance of paracetamol (letamol ) 500mg
Was 5 minutes at 37℃.

DISSOLUTION TEST
ESKAY
Time(minutes) Temperature
30 37℃

LETAMOL
Time (minutes) Temperature
49 37℃

DISCUSSIONS
The quality control tests performed on the solid dosages forms provide valuable data
regarding their physical characteristics, weight uniformity,drug content,dissolution
rate, and microbiology safety .Any deviations from the established specifications may
indicate potenrtial issues with the manufacturing process or formulation. All
significant and unacceptable deviations must be corrected if possible to be able to
proceed with the formulation , else the sample or batch should be discarded. All
official test must be passed before a product can be remarkable.
The quality control was carried out on different brands of paracetamol (eskay and
letamol) , the percentage friability of paracetamol eskay was 0.72% and letamol was
1.18% and the accepted values per the BP values less than 1% hence both brands of
paracetamol have passed the friability test.
For the uniformity of weight test , according to the BP tablets with a strengh of
250mg or more should not deviate from +_ 5 ,results from experiment for both
brands shows that non have deviated from the standard BP. With the disintegration
test eskay used 3 minutes and letamol used 5minutes at 37℃ to disintegrate into
solution.The standard disintegration time according to BP is 3-17 minutes , hence
both brands have passed the test.For the dissolution test Eskay used 30minutes to
dissolute at 37℃ and Letamol used 49minutes to also dissolute at the same
temperature, and according to standard literature at least 80% of the drug should go
into solution at the first 30minutes and comparing this to the results it can be deduced
that the results were in uniformity with the standards.

CONCLUSION
With comparison of the experimental results with the stated standards from BP it can
be concluded that quality control was a success and the tablets were evaluated for
their pharmaceutical quality and have proven to be of good quality.

RECOMMENDATION
In addition to internal quality control measures, it is also advisable to collaborate with
external laboratories and organizations for independent testing. External testing can
provide an unbiased evaluation of the solid dosage forms, offering an additional layer
of assurance regarding their quality. This can include outsourcing certain tests to
accredited laboratories or engaging in collaborative programs with research
institutions or regulatory authorities.
Regular training and qualification of personnel involved in quality control are of
utmost importance. Employees should be equipped with the necessary knowledge and
skills to perform tests accurately and interpret results correctly. Ongoing training
programs should be implemented to keep the staff updated with the latest techniques,
regulatory requirements, and quality control practices.
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