Page No.

FORMULATION AND EVALUATION OF FLOATING

TABLETS OF ASPIRIN

A project report submitted

In partial fulfillment of the requirement

For the award of the degree of

BACHELOR OF PHARMACY

Mohd Zahid Khan

Enrollment No- 131581

Under the guidance of

Dr Ritu Gupta

DEPARTMENT OF PHARMACEUTICS
INVERTIS INSTITUTE OF PHARMACY
INVERTIS UNIVERSITY
BAREILLY-LUCKNOW HIGHWAY, NH-24, BAREILLY, U.P
2016---2017
 Page No.2

CERTIFICATE

This is to certify that the project report entitled Formulation and Evaluation of
Floating Tablets of Aspirin is being submitted by Mohd Zahid khan bearing a
Enrollment no. 131581 in partial fulfillment of the requirement for the award of the
Degree of Bachelor of Pharmacy, for the elective subject Novel Drug Delivery
System at Invertis Institute of Pharmacy, Invertis University, Bareilly. The Institute
wishes him all the success in life
.

Supervisor Head of Department

Dr .Ritu Gupta Mr. Ajit Yadav
Associate professor Associate professor
 Page No.3

ACKNOWLEDGEMENT

It is said that accomplishments must be credited to those who had put up

The foundations of the particular chore. In a work of this magnitude, it was natural to solicit
guidance, help and co-operation from many people and I like to acknowledge all those who
generously provided their time and expertise to maintain the quality of work.

First and foremost I express my profound gratitude and venerable regards to my guide
Dr .Ritu Gupta as a teacher she has always strived to inculcate the scientific attitude in me. I
am thankful to her for his guidance, vital encouragement, incisive criticism and dynamic
assistance. She was always present for me, whenever I needed him and I cherish the amount of
freedom I have enjoyed during this tenure under him.

I would like to express my sincere regards to Mr. Ajit yadav Head of the Department,
who is guardian figure to me. He supported me in my research and instilled confidence to reach
greater heights in my life and Mr. Vipin Agrwal for his help, fruitful knowledge, suggestions
and advice for the work.

This task would have been fruitless without the blessing, support, encouragement and
inspiration o f Mr.Himanshu Joshi and Mr.Shashank Chaturvedi. Here I pay tributes to my
parents for lifting me up in my life. I sincerely thank them for their love, trust, patience &
support without which I would have failed to stand where I am standing today. My deepest sense
of gratitude towards my father, Mr. Ghasee Khan and my mother Mrs. Shakuran Begum who
has always motivated and contributed towards the pursuance of my studies, without worrying
about all odds. My sincere thanks to my brother Mr. Nakshey khan who has always played a
role of a wise advisor and he really deserves heartfelt thanks for her wishes, love and support.

At this moment I really shall not forget my sister Rihana khan who always dreamed of me
reaching to this level. I would really thank all the rest of my family who have directly and
indirectly helped me to achieve my goals.
 Page No.4

I am grateful to Dr .Umesh Gautam chancellor of Invertis University for his words of

encouragement and timely support.

I express my indebtedness to our vice chancellor prof. Jadish Rai for his help and
cooperation throughout my project work.

I express my sincere thanks to Dr. Y.D.S. Arya for his kindness, helpfulness and
motivating thoughts.

I really feel short of words when it comes in expressing my deep sense of gratitude
towards Himanshu Gangwar Devendra Kunwar pal Singh, Rajat Gupta , Bharat Singh
,Anurag pdy , Keshav Sharma ,and Rizwan Khan for all their cooperation, support and
making me believe that I am capable of doing even better.

Words fail to express my gratitude towards our M.pharm seniors Mr. Ashish Gangwar,
Mr. Akhil Chaudhary, and Ms. Sumbul Naaz helped me to achieve my targets.

Date:

Place: Mohd Zahid Khan

 Page No.5

CONTENTS

CHAPTER NO. TITEL NO. PAGE NO.

I NITRODUCTION 6-17

II
REVIEW OF LITERATURE 18-19

III PRE FORMULATION

20-22

IV FORMULATION
23-24

V EVALUATION
25-43

VI RESULT AND 44-46

DISCUSSION
Page No.6
 Page No.7

INTRODUCTION
Floating drug delivery systems (FDDS) are aimed to retain the drug in the stomach and are
useful for drugs that are poorly soluble or unstable in intestinal fluids. The underlying principle
is very simple i.e., to make the dosage form less dense than the gastric fluids so that it can float
on them. The density of the system can be reduced by incorporating a number of low density
fillers into the systems such as hydroxyl cellulose, lactates or microcrystalline cellulose.
However, this system is not ideal because its performance is highly dependent on the presence of
food and fluid in the stomach. The basic idea behind the development of such a system was to
maintain a constant level of drug in the blood plasma inspire of the fact that the drug dose not
undergoes disintegration. The drug usually keeps floating in the These systems have a particular
advantage that they can be retained in the stomach and assist in improving the oral sustained
delivery of drugs that have an absorption window in a particular region of the GIT. These
systems continuously release the drug before it reaches the absorption window, thus ensuring
optimal bioavailability. Different approaches are currently used to prolong the gastric retention
time, like hydro dynamically balanced systems, swelling and expanding systems, polymeric bio-
adhesive systems, modified shape systems1

Definition

Floating system first described by davis in 1968.Floting systems or dynamically controlled

systems are low density systems that have sufficiently buoyancy to float over the gastric contents
and remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged
period of time. Floating systems are low density systems that have sufficient buoyancy to float
over the gastric contents and remain in the stomach for a prolonged period. While the system
floats over the gastric contents, the drug is released slowly at the desired rate, which results in
increased gastro-retention time and reduces fluctuation2

Different technologies 3

Non-effervescent system
 Page No.8

Effervescent system

Non-effervescent system4

In this system commonly used excipients are gel-forming or highly swellable cellulose type
hydrocolloids, polysaccharides and matrix forming polymers such as polycarbonate,
polyacrylate, polymethacrylate and polystyrene. One of the approaches to the formulation of
such floating dosage forms involves intimate mixing of drug with a gel forming hydrocolloid
which swells in contact with gastric fluid after oral administration and maintains a relative
integrity of shape and a bulk density of less than unity within the outer gelatinous barrier. The air
entrapped by the swollen polymer confers buoyancy to these dosage forms. The gel structure acts
as a reservoir for sustained drug release since the drug is slowly released for sustained drug
release since the drug is slowly released by a controlled diffusion through the gelatinous barrier

Effervescent system5

These floating systems are prepared with Swellable polymers such as methocel or
polysaccharides like chitiosan and effervescent component containing sodium bicarbonate, citric
and/or tartaric acid or matrices containing chambers of liquid that gasify at body temperature.
The matrices are fabricated so that upon contact with gastric fluid, carbon dioxide is liberated by
the acidity of gastric contents and is entrapped in the gelyfied hydrocolloid.

Advantages of FDDS6

FDDS is highly advantageous in the treatment of the disorders related to the stomach. As
the prime objective of such systems is to produce a gastro retentive product or a product
which has an enhanced retention time in the stomach
Drugs with considerably short half life can be administered in this manner to get an
appreciable therapeutic activity.
Enhancement of the bioavailability for drugs which can metabolized in the upper GIT.
They also have an advantage over the conventional system as it can be used to overcome
the adversities of gastric retention time as well as the gastric emptying time
The duration of treatment through a single dose, which releases the an active ingredient
over an extended period of time
 Page No.9

The active entity is delivered specifically to the site of action, thus minimizing or
eliminating the side effects

Disadvantages of FDDS7

The major disadvantage of floating system is requirement of a sufficient high level of fluids in
the stomach for the drug delivery to float. However this limitation can be overcome by coating
the dosage form with the help of bioadhesive polymers that easily adhere to the mucosal lining of
the stomach

Gastric retention is influenced by many factors such as gastric motility, pH and presence
of food. These factors are never constant and hence the buoyancy cannot be predicted.
Drugs that cause irritation and lesion to gastric mucosa are not suitable to be formulated
as floating drug delivery systems
High variability in gastric emptying time due to its all (or) non-emptying process.
Patients should not be dosed with floating forms just before going to bed.
Floating system is not feasible for those drugs that have solubility (or) stability problem
in gastric fluids.
The dosage form should be administered with a minimum of glass full of water (200-250
ml).
The drugs, which are absorbed throughout GIT, which under go first-pass metabolism
(Nifedipine, Propranolol etc.), are not desirable candidate.

Mechanism of floating systems8

Various attempts have been made to retain the dosage form in the stomach as a way of increasing
the retention time. FDDS have a bulk density less than gastric fluids and so remain buoyant in
the stomach without affecting the gastric emptying rate for a prolonged period of time. While the
system is floating on the gastric contents, the drug is released slowly at the desired rate from the
system. After release of drug, the residual system is emptied from the stomach. This results in an
increased GRT and a better control of the fluctuations in plasma drug concentration
 Page No.10

Figure 1: Mechanism of floatation via CO2 liberation

Methods of Floating Dosage Form9

Using gel-forming hydrocolloids such as hydrophilic gums, gelatin, alginates, cellulose

derivatives, etc.
Using low-density enteric materials such as methacrylic polymer, cellulose acetate
phthalate.
By reducing particle size and filling it in a capsule.

By forming carbon dioxide gas and subsequent entrapment of it in the gel network.

By forming carbon dioxide gas and subsequent entrapment of it in the gel network.

By preparing hollow micro-balloons of drug using acrylic polymer and filled in capsules.

By incorporation of inflatable chamber, which contained in a liquid e.g. solvent that

gasifies at body temperature to cause the chambers to inflate in the stomach
 Page No.11

Methods for Preparing Floating Dosage Form

Following approaches can be used for preparing floating dosage forms.

Using gel-forming hydrocolloids such as hydrophilic gums, gelatin, alginates, cellulose

derivatives, etc.

Using low-density enteric materials such as methacrylic polymer, cellulose acetate

phthalate.

By reducing particle size and filling it in a capsule.

By forming carbon dioxide gas and subsequent entrapment of it in the gel network.

FACTORS AFFECTING THE FDDS10

Various attempts have been made to retain the dosage form in the stomach as a way of increasing
the retention time. Most of these approaches are influenced by a number of factors that affect
their bioavailability and efficacy of the gastro retentive system
Density: Gastric retention time (GRT) is a function of dosage form buoyancy that is dependent
on the density.

Size: Dosage form units with a diameter of more than 7.5 mm are reported to have an increased
GRT compared with those with a diameter of 9.9 mm.

Shape of dosage form: Tetrahedron and ring shaped devices with a flexural modulus of 48 and
22.5 kilo pounds per square inch (KSI) are reported to have better GRT 90% to 100% retention at
24 h compared with other shapes.

Single (or) multiple unit formulation: Multiple unit formulations show a more predictable
release profile and insignificant impairing of performance due to failure of units, allow co-
administration of units with different release profiles (or) containing incompatible substances and
permit a larger margin of safety against dosage form failure compared with single unit dosage
forms.
 Page No.12

Fed or unfed state: Under fasting conditions, the GI motility is characterized by periods of
strong motor activity (or) the Migrating Myoelectric Complex (MMC) that occurs every 1.5 to 2
h. The MMC sweeps undigested material from the stomach and, if the timing of administration
of the formulation coincides with that of the MMC, the GRT of the unit can be expected to be
very short. However, in the fed state, MMC is delayed and GRT is considerably longer.

Nature of meal: Feeding of indigestible polymers (or) fatty acid salts can change the motility
pattern of the stomach to a fed state, thus decreasing the gastric emptying rate and prolonging
drug release.

Caloric content: GRT can be increased by four to 10 h with a meal that is high in proteins and
fats.

Frequency of feed: The GRT can increase by over 400 minutes when successive meals are given
compared.

Pharmacokinetic and Pharmacodynamic of FDDS11

The aim of this section is to delineate these aspects in order to suggest rational selection of drugs
for which FDDS would be a beneficial strategy
Absorption window:
Validation that the drug is within the category of
Narrow absorption window agents currently various experimental techniques are available that
permit us to verify the absorption properties of the tested molecule, to determine the mechanism
of intestinal absorption and to elucidate the permeability at different regions of the GI tract.
Enhanced bioavailability:
Once it has been ascertained that the compound in question is defined as narrow absorption
window, the possibility of improving bioavailability by continuous administration of the
compound to the specific site should be tested. For example, we have found that certain
bisphosphonates, including alendronate, are absorbed directly from the stomach.
Enhanced first pass biotransformation
In a similar fashion to increased efficacy of active transporters exhibiting capacity limited
activity, the pre-systemic metabolism of the tested compound may be considerably increased
 Page No.13

when the drug is presented to the metabolic enzymes (cytochrome P450, in particular CYP3A4)
in a sustained manner, rather than by a bolus input.

Improved Bioavailability.
In apparent contrast to the higher density of CYP3A4 at the upper part of the intestine, P-gp
mRNA levels increase longitudinally along the intestine such that the highest levels are located
in the colon. Therefore, for drugs that are P-gp substrate and do not undergo oxidative
metabolism, such as Dioxin, floating systems may elevate absorption compared to the immediate
and CR dosage forms.

DRUGPROFILE
 Page No.14

Description

Aspirin is used to reduce fever and relieve mild to moderate pain from conditions such as
muscle aches, toothaches, common cold, and headaches. It may also be used to reduce pain and
swelling in conditions such as arthritis. Aspirin is known as a salicylate and a nonsteroidal anti-
inflammatory drug (NSAID).

Chemical name: 2acetoxybenzoic acid

Molecular formula: C9H8O4

Molecular weight: 180.159 g/mol

Melting range: 1350C

Volume of distribution: 11.9 L

Structure:

Bioablivility
 Page No.15

This metabolism occurs primarily by hepatic conjugation with glycin or glucuronic acid, each
involving different metabolic pathways. The predominant pathway is the conjugation with
glycin, which is saturable. With low doses of aspirin approximately 90% of salicylate is
metabolized through this pathway.

Hafe life: 2hr may increase to 30 hr depending dose

Ultra violet: 243 nm

Dose:

Aspirin comes as a regular tablet, a delayed-release tablet, a chewable tablet, a powder, a gum,
and a rectal suppository.

It's typically taken every four to six hours to treat fever and pain. It's usually taken once a day to
lower the risk of a heart attack or stroke. Typical dosages range from 50 milligrams (mg) to
6,000 mg, daily.

You should swallow the delayed-release tablets with a full glass of water. These tablets don't
work immediately after they are taken, so you shouldn't use them for quick pain relief.

The chewable tablets can be crushed, chewed, or swallowed whole. You should drink a full glass
of water right after taking this form of the medication.

Overdose

Symptoms of an aspirin overdose include stomach pain, nausea and vomiting, and ringing in the
ears (tinnitus). If you suspect an overdose, contact a poison control center or emergency room
immediately.

Missed Dose

If you miss a dose of aspirin, take it as soon as you remember.

 Page No.16

However, if it's almost time for your next dose, skip the missed dose and continue on your
regular dosing schedule. Don't double up on doses to make up for a missed one.

Mechanism of action

Much of this is believed to be due to decreased production of prostaglandins and

TXA2. Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to
its irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required
for prostaglandin and thromboxane synthesis.

Fig 2. Mechanism of action

Uses
 Page No.17

Aspirin is used to treat pain, and reduce fever or inflammation. It is sometimes Aspirin should be
used for cardiovascular conditions only under the supervision of a doctor. Used to treat or
prevent heart attacks, strokes, and chest pain (angina).

Side Effects

It should be following side effects associated with drug.

Vomiting

Stomach pain

Heartburn

Drowsiness

Nausea
Page No.18
 Page No.19

REVIEW OF LITERATURE

1. Iftequar S, et al. (2016) Formulated and evaluated floating drug delivery system Ramipri.

2. Soniya C. et al (2015) formulated and evaluated floating tablets Nizatidine.

3. Kadam A.M. et al (2014) formulated and evaluated Anti-Ulcer floating tablet using
Swellable Polymers.

4. NIKAM. M .S. et al, (2014) preparation and evaluated gastroretentive floating tablet
containing enalapril maleate.

5. Khatri N, et al (2014) formulated and evaluated of floating matrix tablet levofloxacin

hemihydrate.

6. Tanwar Y.S.et al (2013) formulated and in vitro evaluated floating tablets Losartan
Potassium.

7. BISWAS, M. et al (2013) formulated and in vitro evaluated gastroretentive floating drug

delivery system Ritonavir

8. Saritha. D. et al. (2012) formulated and evaluated gastroretentive floating tablets.

Domperidone Maleate

9. Singh S, et al (2011) formulated and evaluated Floating tablet of Captopril.

10. Padmavathy .J. et al, (2011) formulated and evaluated ofloxacin floating tablets using
HPMC.
Page No.20
 Page No.21

PRE FORMULATION

UV SPECTROSCOPY:

An U.V spectrophotometric method based on the measurement of absorbance at 245 nm in

phosphate buffer oh pH 5.8 was used for the estimation of paracetamol. The method obeyed
Beers law in the concentration range 0 - 10 g/ml.

Angle of repose:

The angle of repose of powdered gum was determined by the funnel method. The accurately
weighed granules were taken in a funnel. The height of the funnel was adjusted in such a way
that the tip of the funnel just touched the apex of the heap of granules. The granules were
allowed to flow through the funnel freely onto the surface. The diameters of powder cone was
measured and angle of repose was calculated using the equation.

=tan1(h/r )

Bulk density

Both bulk density (BD) and tapped density (TBD) were determined. A quantity of 2 gm of
powder from each formula, previously lightly shaken to break any agglomerates formed, was
introduced into a 10 ml measuring cylinder. After the initial volume was observed, the cylinder
was allowed to fall under its own weight on to a hard surface form the height of 2.5 cm at 2
second intervals. The tapping was continued until no further change in volume was noted. LBD
and TBD were calculated using the formulas.

BD = Weight of the powder/volume of the packing

 Page No.22

TBD = Weight of the powder/tapped volume of the packing

Compressibility index /Carrs index

The flow of property was also determined by measuring the compressibility index. It is an
important measure that can be obtained from the bulk and tapped densities. According to the
theory, the less compressible materials are more flowable. A material having values of less than
20 to 30% is defined as the free flowing martial, based on the apparent bulk density and tapped
density, the drug was determined by using the formulas.9
density
comperessibility index=bulk 100
tap density

Table1.precompression parameters of Aspirin floating tablets,

S Test F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
N
o
1 Bulk 0.62 065 0.60 0.62 0.64 0.69 0.61 0.62 0.62 0.60
density
(gm/ml)

2 Tapped 0.87 0.87 0.86 0.80 0.873 0.87 0.89 0.85 0.876 0.85
density
(gm/ml)

3 Care 28.73 29.83 28.80 30.25 29.98 30.35 31.23 29.98 28.80 29.8
index 0
4 Angle 25 25 25 24 26 25 26 28 25 25
of .2
.24 .34 .45 .45 .56 .56 .30 .45
repose
(degree) 5 .24
Page No.23
 Page No.24

FORMULATION

Materials and Methods

Aspirin CDH New Delhi, Lactose CDH New Delhi, Magnesium sterate CDH New Delhi, Talc
CDH New Delhi,

Table2: of Formulation

Sr. Name of Amount (gm/tablet)

No. Ingredient
Formulation F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Code
1 Aspirin 80 80 80 88 80 80 80 80 80 80

2 HPMC 80 75 77 73 79 79 50 80 75 73
3 Sodium 80 75 74 10 76 72 10 50 60 22
bicarbonate
4 Citric acid 10 10 10 52 10 10 14 10 15 40
5 PVP 50 60 54 52 51 50 10 10 10 52

6 Magnesium 10 10 10 10 10 10 79 80 75 10
sterate
7 Talc 5 15 10 12 9 14 72 5 10 12
Page No.25
 Page No.26

EVALUATION

1. Weight variation test

The weight variation test for given tablet was successfully done

Formula

% deviation or % weight deviation =

Indivsual weight Avrage weight

100
Avrage weight

Procedure

Taken 20 tablet to perform weight variation test.

Weighed 20 tablet collectively with the aid of electronic balance.
Calculated the average weight of 20 tablets collectively.
Now weighed the individual tablet by using electronic balance.
Calculation of deviation was done by using mentioned formula.
 Page No.27

Table 3. Weight variation test for F1

S No Individual weight Average weight % Deviation Inference

1 320 315 1.58 Pass
2 290 315 -3.17 Pass
3 290 315 -3.17 Pass
4 319 315 1.26 Pass
5 295 315 -6.34 Fail
6 295 315 -6.34 Fail
7 285 315 -9.52 Fail
8 310 315 -1.58 Pass
9 325 315 3.17 Pass
10 305 315 -3.17 Pass
11 310 315 -1.58 Pass
12 310 315 -1.58 Pass
13 290 315 -3.17 Pass
14 285 315 -9.52 Fail
15 318 315 0.95 Pass
16 308 315 -2.22 Pass
17 310 315 -1.58 Pass
18 320 315 1.58 Pass

19 320 315 1.58 Pass

20 325 315 3.17 Pass

Table 4. Weight variation test for F2

 Page No.28

S No Individual weight Average weight % Deviation Inference

1 290 315 -3.17 Fail
2 290 315 -3.17 Fail
3 310 315 -1.58 Fail
4 300 315 -4.76 Pass
5 310 315 -1.58 Pass
6 320 315 1.58 Pass
7 320 315 1.58 Pass
8 290 315 -3.17 Pass
9 318 315 0.98 Pass
10 318 315 0.98 Pass
11 300 315 -4.76 Pass
12 300 315 -4.76 Pass
13 290 315 -3.17 Pass
14 295 315 -6.34 Fail
15 295 315 -6.34 Fail
16 308 315 -2.22 Pass
17 310 315 -1.58 Pass
18 320 315 1.58 Pass
19 285 315 -9.52 Fail
20 280 315 -11.11 Fail

Table5. Weight variation test for F3

S No Individual weight Average weight % Deviation Inference

1 280 315 -11.11 Fail
2 290 315 -7.93 Fail
3 285 315 -8.57 Fail
4 310 315 3.33 Pass
 Page No.29

5 285 315 -8.57 Fail

6 285 315 -9.52 Fail
7 288 315 -8.57 Fail
8 290 315 -7.93 Fail
9 305 315 -3.17 Pass
10 310 315 -1.58 Pass
11 280 315 -11.11 Fail
12 280 315 -11.11 Fail
13 310 315 -1.58 Pass
14 318 315 0.95 Pass
15 320 315 1.58 Pass
16 320 315 1.58 Pass
17 285 315 -9.52 Fail
18 295 315 -6.34 Fail
19 290 315 -7.93 Fail
20 310 315 -1.58 Pass

Table 6. Weight variation test for F4

S No Individual weight Average weight % Deviation Inference

1 290 315 -3.17 Fail
2 290 315 -3.17 Fail
3 310 315 -1.58 Fail
4 300 315 -4.76 Pass
5 310 315 -1.58 Pass
 Page No.30

6 320 315 1.58 Pass

7 320 315 1.58 Pass
8 290 315 -3.17 Pass
9 318 315 0.98 Pass
10 318 315 0.98 Pass
11 300 315 -4.76 Pass
12 300 315 -4.76 Pass
13 290 315 -3.17 Pass
14 295 315 -6.34 Fail
15 295 315 -6.34 Fail
16 308 315 -2.22 Pass
17 310 315 -1.58 Pass
18 320 315 1.58 Pass
19 285 315 -9.52 Fail
20 280 315 -11.11 Fail

Table 7.Weight variation test for F5

S No Individual weight Average weight % Deviation Inference

1 320 315 1.58 Pass
2 290 315 -3.17 Pass
3 290 315 -3.17 Pass
4 319 315 1.26 Pass
5 295 315 -6.34 Fail
6 295 315 -6.34 Fail
 Page No.31

7 285 315 -9.52 Fail

8 310 315 -1.58 Pass
9 325 315 3.17 Pass
10 305 315 -3.17 Pass
11 310 315 -1.58 Pass
12 310 315 -1.58 Pass
13 290 315 -3.17 Pass
14 285 315 -9.52 Fail
15 318 315 0.95 Pass
16 308 315 -2.22 Pass
17 310 315 -1.58 Pass
18 320 315 1.58 Pass
19 320 315 1.58 Pass
20 325 315 3.17 Pass

Table 8.weight variation test for F6

S No Individual weight Average weight % Deviation Inference

1 320 315 1.58 Pass
2 290 315 -3.17 Pass
3 290 315 -3.17 Pass
4 319 315 1.26 Pass
5 295 315 -6.34 Fail
6 295 315 -6.34 Fail
7 285 315 -9.52 Fail
 Page No.32

8 310 315 -1.58 Pass

9 325 315 3.17 Pass
10 305 315 -3.17 Pass
11 310 315 -1.58 Pass
12 310 315 -1.58 Pass
13 290 315 -3.17 Pass
14 285 315 -9.52 Fail
15 318 315 0.95 Pass
16 308 315 -2.22 Pass
17 310 315 -1.58 Pass
18 320 315 1.58 Pass
19 320 315 1.58 Pass
20 325 315 3.17 Pass

Table 9. Weight variation test for F7

S No Individual weight Average weight % Deviation Inference

1 280 315 -11.11 Fail
2 290 315 -7.93 Fail
3 285 315 -8.57 Fail
4 310 315 3.33 Pass
5 285 315 -8.57 Fail
6 285 315 -9.52 Fail
7 288 315 -8.57 Fail
 Page No.33

8 290 315 -7.93 Fail

9 305 315 -3.17 Pass
10 310 315 -1.58 Pass
11 280 315 -11.11 Fail
12 280 315 -11.11 Fail
13 310 315 -1.58 Pass
14 318 315 0.95 Pass
15 320 315 1.58 Pass
16 320 315 1.58 Pass
17 285 315 -9.52 Fail
18 295 315 -6.34 Fail
19 290 315 -7.93 Fail
20 310 315 -1.58 Pass

Table 10. Weight variation test for F8

S No Individual weight Average weight % Deviation Inference

1 320 315 1.58 Pass
2 290 315 -3.17 Pass
3 290 315 -3.17 Pass
4 319 315 1.26 Pass
5 295 315 -6.34 Fail
6 295 315 -6.34 Fail
7 285 315 -9.52 Fail
8 310 315 -1.58 Pass
 Page No.34

9 325 315 3.17 Pass

10 305 315 -3.17 Pass
11 310 315 -1.58 Pass
12 310 315 -1.58 Pass
13 290 315 -3.17 Pass
14 285 315 -9.52 Fail
15 318 315 0.95 Pass
16 308 315 -2.22 Pass
17 310 315 -1.58 Pass
18 320 315 1.58 Pass
19 320 315 1.58 Pass
20 325 315 3.17 Pass

Table 11.Weight variation test for F9

S No Individual weight Average weight % Deviation Inference

1 290 315 -3.17 Fail
2 290 315 -3.17 Fail
3 310 315 -1.58 Fail
4 300 315 -4.76 Pass
5 310 315 -1.58 Pass
6 320 315 1.58 Pass
7 320 315 1.58 Pass
8 290 315 -3.17 Pass
9 318 315 0.98 Pass
10 318 315 0.98 Pass
11 300 315 -4.76 Pass
12 300 315 -4.76 Pass
13 290 315 -3.17 Pass
14 295 315 -6.34 Fail
15 295 315 -6.34 Fail
16 308 315 -2.22 Pass
17 310 315 -1.58 Pass
18 320 315 1.58 Pass
19 285 315 -9.52 Fail
 Page No.35

20 280 315 -11.11 Fail

Table12. Weight variation test for F10

S No Individual weight Average weight % Deviation Inference

1 280 315 -11.11 Fail
2 290 315 -7.93 Fail
3 285 315 -8.57 Fail
4 310 315 3.33 Pass
5 285 315 -8.57 Fail
6 285 315 -9.52 Fail
7 288 315 -8.57 Fail
8 290 315 -7.93 Fail
9 305 315 -3.17 Pass
10 310 315 -1.58 Pass
11 280 315 -11.11 Fail
12 280 315 -11.11 Fail
13 310 315 -1.58 Pass
14 318 315 0.95 Pass
15 320 315 1.58 Pass
16 320 315 1.58 Pass
17 285 315 -9.52 Fail
18 295 315 -6.34 Fail
19 290 315 -7.93 Fail
20 310 315 -1.58 Pass
 Page No.36

2. Friability test

Procedure

Roche friabilatar A number and deducted tablets (usually 6mg) are placed in tumbling apparatus
made the plastic that revolves at 25 rpm and drops the tablets to distance of 6 niche with each
revaluation normally the tablet are subjected to free for 100 revolution or 10 minutes. The tablets
are then deducted and are weighed the friability is calculated by formula. 25 rpm for 25 min.

Inetial weightFinal weight

Freability= X 100
Initial weight
 Page No.37

Fig Friability Tester (Roche Friabilatar)

Table 13.Friability

S No Formulation Code Friability %

1 F1 0.8
2 F2 1.0
3 F3 1.2
4 F4 1.0
5 F5 0.8
6 F6 1.1
7 F7 1.2
8 F8 1.3
9 F9 1.0 3. Hardness Test
10 F10 1.1
In hardness test we Monsanto and Pfizer
We put the individual tablet in to the Monsanto and Pfizer,
We repeated the process 6 trims
Apply the force and when the tablet starts braking the records the reading from the points
 Page No.38

Table 14. For Hardness

S No Formulation No Hardness kg/cm

1 F1 6
2 F2 7
3 F3 9
4 F4 8
5 F5 5
6 F6 6
7 F7 6
8 F8 8
9 F9 9
10 F10 6

4. Dissolution Test

Procedure

Placed the 900 ml of water which should be free from dissolution air and warm set up to
37 0C
Placed the tablets in the basket and set the apparatus
Start the motor and adjust rotation speed of 50 rpm
Now take the reading after 5 min 10, 15, 30, and 45 minutes by diluting 1 ml of sample
with 10 ml of water.

Table15. Dissolution

S No Time minutes % Amount release Cumulative % Release

1 5 2 2
 Page No.39

2 10 4 6
3 30 3 9
4 60 7 16
5 120 12 28

Dissolution curve

5. Content Uniformity

In this test, 20 tablets were randomly selected and the percent drug content was determined, the
tablets contained not less than 85% or more than 115% of the labeled drug content can be
considered as the test was passed.

5. Assay

The drug content in each formulation was determined by triturating 20 tablets and powder
equivalent to average weight was added in 100ml of 0.1N Hydrochloric acid, followed by
stirring. The solution was filtered through a 0.45 membrane filter, diluted suitably and the
 Page No.40

absorbance of resultant solution was measured spectrophotometrically at 315nm using 0.1 N

Hydrochloric acids as blank.

6. Disintegration Test:

Disintegration test is widely used in the pharmaceutical industry for

evalution of disintegration capability of formulations (ex: tablets) and quality
control of different dosage forms.

Applications of Disintegration test :

1. Disintegration test is a simple test which helps in the preformulation stage

to the formulator.

2. It helps in the optimization of manufacturing variables, such as

compression force time

3. This test is also a simple in-process control tool to ensure uniformity from
batch to batch and among different tablets.

4. It is also an important test in the quality control of tablets.

Advantages of Disintegration tests:

This test is simple in concept and in practice. It is very useful in

reformulation, optimization and in quality control.

Disadvantages:

Disintegration test cannot be relied upon for the assurance of bioavailability.

The disintegration test for each dosage form is given in the pharmacopoeia. There are some
general tests for typical types of dosage forms. However, the disintegration test prescribed in the
individual monograph of a product is to be followed. If the monograph does not specify any
 Page No.41

specific test, the general test for the specific dosage form may be employed. Some of the types of
dosage forms and their disintegration tests are:

1. Uncoated tablets

Tested using distilled water as medium at 37+/-2 C at 29-32 cycles per minute; test is completed
after 15 minutes. It is acceptable when there is no palpable core at the end of the cycle (for at
least 5 tablets or capsules) and if the mass does not stick to the immersion disc.

2. Coated tablets

The same test procedure is adapted but the time of operation is 30 minutes.

3. Enteric coated/ Gastric resistant tablets

The test is carried out first in distilled water (at room temperature for 5 min.; USP and no
distilled water per BP and IP), then it is tested in 0.1 M HCL(upto 2 hours; BP) or Stimulated
gastric fluid (1 hour; USP) followed by Phosphate buffer, pH 6.8 (1 hour; BP) or Stimulated
intestinal fluid without enzymes (1 hour; USP).

Fig Disintegration Apparatus

 Page No.42

Medium: The assembly in suspended in the liquid medium in a suitable

vessel, preferably a 1 litre beaker. The volume of the liquid is such that the
wire mesh at its highest point is at least 25mm below the surface of the
liquid, and at its lower point is at least 25 mm above the bottom of the
beaker. At no time should the top of the basket-rack assembly become
submerged. There is a thermostatic arrangement for heating the liquid and
maintaining the temperature at 37oC 2 degree celsius.
 Page No.43

RESULTS AND DISCUSSION

The tablets were prepared by effervescent technique using sodium bicarbonate as a gas
generating agent. Sodium bicarbonate induced carbon dioxide generation in the presence of
dissolution medium (0.01 N HCl). The gas generated is trapped and protected within the gel,
formed by hydration of polymer, thus decreasing the density of the tablet. As the density of the
tablet falls below 1 g/ ml, the tablet becomes buoyant he result shows that the total floating time
for the formulations was more than 24 hours irrespective to the amount of sodium bicarbonate
whereas floating lag time decreases with increasing amount of sodium bicarbonate. The amount
of carbon dioxide produced is exclusively proportional to the quantity of sodium bicarbonate in
the tablet. Decrease in floating lag time of the formulations can be attributed to the availability of
an increased amount of carbon dioxide as the concentration of sodium bicarbonate was
 Page No.44

increased, being entrapped in the formed gel to give rapid buoyancy. Sodium bicarbonate at the
level of 20 mg per tablet showed floating lag time of 83 to 106 seconds.

Gastro Retentive Floating tablets of Aspirin. HCl were prepared and optimized by 3 2 factorial
design in order to select the best combination of different release rate modifiers, HPMCK4M,
Guar Gum and also to achieve the desired prolonged release of drug from the dosage form(by
retaining drug at gastric environment). The two factorial parameters involved in the development
of formulations are, quantity of HPMCK4M & Guar Gum polymers as independent variables
(X1, X2), and In vitro dissolution parameters such as t10%, t50% , t75% & t90% as dependent variables.
Totally nine formulations were prepared using 3 levels of 2 factors and all the formulations
containing 315 mg Aspirin. HCl (equivalent to 315 mg of Aspirin) were prepared as a sustained
release tablet dosage form by Direct Compression technique as per the formulae given in table2.
 Page No.45

CONCLUSION

The floating tablets of ranitidine hydrochloride were prepared by dry

granulation method based on effervescent approach. HPMC and Polyox were
used as the polymers and sodium bicarbonate was used as a gas generating
approach. It was seen that increasing the concentration of polymers (HPMC
K15MCR and Polyox WSR303) delayed the drug release profile. However,
there was no effect on drug release profile upon changing the viscosity
grades of HPMC (K15MCR to K100MCR). Increasing the amount of sodium
bicarbonate decreased the floating lag time. But the amount of sodium
bicarbonate did not have any effect on total floating time of formulations.
Changing the concentrations of sodium bicarbonate and stearic acid had no
significant effect on drug release profile. Hence from the present study, it
can be concluded that hypromellose (HPMC K15MCR) and PEO (Polyyox
WSR303) in appropriate concentration can be used to develop sustained
release floating tablets of ranitidine hydrochloride by incorporating
appropriate concentration of sodium bicarbonate for gas generation. Such
system can remain buoyant for 24 hours along with the sustained drug
release for the same duration.
 Page No.46

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