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BACHELOR OF PHARMACY
JUNAID MALIK
EnrollmentNo-131576
DEPARTMENT OF PHARMACEUTICS
INVERTIS INSTITUTE OF PHARMACY
INVERTIS UNIVERSITY
BAREILLY-LUCKNOW HIGHWAY, NH-24, BAREILLY, U.P
2016---2017
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CERTIFICATE
This is to certify that the project report entitled Formulation and Evaluation of
Sustained Release Tablets of Ibuprofen is being submitted by Junaid Malik
bearing a Enrollment no. 131559 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.
.
ACKNOWLEDGEMENT
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
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
This task would have been fruitless without the blessing, support, encouragement and
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. Intzar Ahmad and my mother Mrs. Shabnam Ahmad who
has always motivated and contributed towards the pursuance of my studies, without worrying
about all odds. My sincere thanks to my brother Azam malik who has always played a role of a
wise advisor and he really deserves heartfelt thanks for her wishes, love and support.
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At this moment I really shall not forget my sister Arshi Malik who always dreamed of me
reaching to this level. I would really thank all the rest of my family who have directly and
I express my indebtedness to our vice chancellor prof. Jadish Rai for his help and
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, Kunwar Pal Singh, Bharat Singh, Keshav Sharma, and Parvez, 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:
CONTENTS
I 6-16
NITRODUCTION
II 17-18
REVIEW OF LITERATURE
IV FORMULATION 23-24
V EVALUATION 25-36
Chapter I
Introduction
INTRODUCTION
Oral route is the most oldest and convenient route for the administration of
therapeutic agents because of low cost of therapy and ease of administration
leads to higher level of patient compliance. Approximately 50% of the drug
delivery systems available in the market are oral drug delivery systems and
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historically too, oral drug administration has been the predominant route for
drug delivery. It does not pose the sterility problem and minimal risk of
damage at the site of administration.
During the past three decades, numerous oral delivery systems have been
developed to act as drug reservoirs from which the active substance can be
released over a defined period of time at a predetermined and controlled
rate. The oral controlled release formulation have been developed for those
drug that are easily absorbed from the gastrointestinal tract (GIT) and have a
short half-life are eliminated quickly from the blood circulation. As these will
release the drug slowly into the GIT and maintain a constant drug
concentration in the plasma for a longer period of time.
Definition
Extended release means the pill is formulated so that the drug is released
slowly over time. This has the advantage of taking pills less often. Also
means that there may be fewer side effects as the levels of the of drug in the
body are more consistent in extended release formulations.
Advantages
Sustained drug delivery: As mentioned earlier, drug absorption from oral controlled release (CR)
dosage forms is often limited by the short GRT available for absorption. However, HBS type
dosage forms can retain in the stomach for several hours and therefore, significantly prolong the
GRT of numerous drugs. These special dosage forms are light, relatively large in size, and do not
easily pass through pylorus, which has an opening of approx. 0.1 1.9 cms. Site specific drug
delivery a floating dosage form is a feasible approach especially for drugs which have limited
absorption sites in upper small intestine. The controlled, slow delivery of drug to the stomach
provides sufficient local therapeutic levels and limits the systemic exposure to the drug. This
reduces side effects that are caused by the drug in the blood circulation. In addition the prolonged
gastric availability from a site directed delivery system may also reduce the dosing frequency.
The eradication of Helicobacter pylori requires the administration of various medicaments
several times a day, which often results in poor patient compliance. More reliable therapy can be
achieved by using GRDDS. Floating alginate beads have been used for the sustained release of
Amoxycillin trihydrate. Thus, it can be expected that the topical delivery of antibiotic through a
FDDS may result in complete removal of the organisms in the fundal area due to bactericidal
drug levels being reached in this area, and might lead to better treatment of peptic ulcer.
Pharmacokinetic advantages
As sustained release systems, floating dosage forms offer various potential advantages. Drugs
that have poor bioavailability because their absorption is limited to upper GI tract can be
delivered efficiently thereby maximizing their absorption and improving their absolute
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bioavailability. Floating dosage forms with SR characteristics can also be expected to reduce the
variability in transit performance. In addition, it might provide a beneficial strategy for gastric
and duodenal cancer treatment.
Disadvantages
1. 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.
2. Floating system is not feasible for those drugs that have solubility or stability problem in
gastric fluids.
3. The dosage form should be administered with a minimum of glass full of water (200-250 ml).
4. The drugs, which are absorbed throughout gastro-intestinal tract, which undergo first pass
metabolism (Nifedipine, propranolol etc.), are not desirable candidate.
5. Some drugs present in the floating system causes irritation to gastric mucosa.
Reservoir devices:
A core of drug (reservoir) surrounded by a polymeric membrane characterizes them. The nature
of the membrane determines the rate of drug release. The characteristics of reservoir diffusion
systems are
1. Zero order drug release is possible.
2. The release rate is dependent on the type of polymer.
3. High molecular weight compounds are difficult to deliver through the device.
Matrix devices:
It consists of drug dispersed homogenously in a matrix. The characteristics of matrix diffusion
systems are
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In a bioerodible matrix, the drug is homogenously dispersed in a matrix and it is released either
by swelling controlled mechanism or by hydrolysis or by enzymatic attack.
One of the least complicated approaches to the manufacture of sustained release dosage forms is
the direct compression of drug, release retardant, and additives to form a tablet in which drug is
embedded in a matrix core of retardant. Alternatively drug retardant blend may be granulated
prior to compression. Such tablets are called as matrix tablets. Three classes of release retarding
materials are used for the formulation of matrix tablets. They include
On exposure to aqueous fluid, hydrophilic matrices take up water, and polymer starts hydrating
to form a gel layer. An initial burst of soluble drug may occur due to surface leaching when a
matrix containing a swellable glassy polymer comes in contact with an aqueous medium, there is
an abrupt change from a glassy to a rubbery state which is associated with swelling process with
time, water infiltrator deep into the case increasing the thickness by the gel layer. Concomitantly
the outer layer becomes fully hydrated and states dissolving or eroding. When water reaches the
center of the system and the concentration of drug fells below the solubility value, the release
rate of drug begins to reduce. At the same time, an increase in thickness of the barrier layer with
time increases the diffusion path length, reducing the rate of drug release. Drug release kinetic
associated with these gel layer dynamic, range initially from Fickian to annomalous (Non
Fickian) and subsequently from quasi Constant ( near Zero order ) to constant. In general, two
major factors control the drug release from swelling controlled matrix system. They include
many processes given below.
1. The rate of aqueous medium infiltration into the matrix, followed by a relaxation process
(hydration, gelatin or swelling).
As a result of these simultaneous processes, two front are evident, a swelling front, where the
polymer get hydrated, and an eroding front. The distance between these two fronts are called
diffusion layer thickness. Diffusion layer thickness depends on the selective rate at which the
swelling and eroding fronts move in relation to each other. If the polymer gets slowly, solvent
can penetrate deep into the glassy matrix the dissolving the drug; there for gel layer thickness
and it stability are council in controlling drug release. Swelling of HPMC matrix tablet was
higher for higher a molecular weight. They attributed this to the large hydrodynamic volume
occupied by higher molecular weight chain when hydrated. As the polymer chain becomes more
hydrated and the gel becomes more dilute, the disentanglement concentration may be reached
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that is the critical polymer concentration below which the polymer chain disentangle and
detached from gelled matrix.
DRUG PROFILE
DESCRIPTION
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Structure:
Melting point: 76 0C
Half life: Ibuprofen is rapidly metabolized and eliminated in the urine. The excretion of
ibuprofen is virtually complete 24 hours after the last dose. The serum half-life is 1.8 to 2.0
hours.
Ultra violet:
Bioavailability
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Ibuprofen is rapidly absorbed, and both peak plasma concentrations and maximal analgesic
onset are achieved within 1.5-2 hours of oral administration. The first is a
sodium ibuprofen formulation containing 256 mg of ibuprofen sodium dehydrate per tablet
(equivalent to 200 mg ibuprofen acid)
Volume of distribution
Protein binding is saturable and at concentrations >20 g/mL binding is non-linear. Based on
oral dosing data there is an age- or fever- related change in volume of distribution for ibuprofen.
Febrile children <11 years old have a volume of approximately 0.2 L/kg while adults have a
volume of approximately 0.12 L/kg.
Initial dose: 400 to 800 mg orally every 6 to 8 hours. Maintenance dose: May be increased to a
maximum daily dose of 3200 mg based on patient response and tolerance.
Initial dose: 400 to 800 mg orally every 6 to 8 hours. Maintenance dose: May be increased to a
maximum daily dose of 3200 mg based on patient response and tolerance.
Oral: Mild to moderate pain: 200 to 400 mg orally every 4 to 6 hours as needed. Doses greater
than 400 mg have not been proven to provide greater efficacy. IV: (Patients should be well
hydrated before IV ibuprofen administration) Pain: 400 to 800 mg intravenously over 30 minutes
every 6 hours as needed.
Oral: 200 to 400 mg orally every 4 to 6 hours as needed. IV: (Patients should be well hydrated
before IV ibuprofen administration) Fever: Initial: 400 mg intravenously over 30 minutes
Maintenance: 400 mg every 4 to 6 hours or 100 to 200 mg every 4 hours as needed.
Greater than 6 months 12years, 5 mg/kg/dose for temperature less than 102.5 degrees F (39.2
degrees C) orally every 6 to 8 hours as needed.10 mg/kg/ dose for temperature greater than or
equal to 102.5 degrees F (39.2 degrees C) orally every 6 to 8 hours as needed. The recommended
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maximum daily dose is 40 mg/kg. OTC pediatric labeling (analgesic, antipyretic): 6 months to
11 years: 7.5 mg/kg/dose every 6 to 8 hours; Maximum daily dose: 30 mg/kg
Infants and Children: 4 to 10 mg/kg orally every 6 to 8 hours as needed. The recommended
maximum daily dose is 40 mg/kg. OTC pediatric labeling (analgesic, antipyretic): 6 months to 11
years: 7.5 mg/kg/dose every 6 to 8 hours; Maximum daily dose: 30 mg/kg
CHAPTER II
REVIEW OF
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LITERATURE
REVIEW OF LITERATURE
2. Katakam P, et al (2014) formulated and evaluated sustained release venlafaxine tablets using
hydrophilic-hydrophobic polymer combinations by melt granulation.
4. Mote. P.B. et al, (2013) formulated and evaluated Sustained Release Matrix Tablets Of Anti-
Asthmatic Agent Using Various Polymers.
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5. Asija. R et al.(2012) formulated and evaluated Diclofenac sodium sustained release tablets
using melt granulation technique.
6. Kalvimoorthi.V, et al. (2011) formulated development and evaluated aspirin delayed release
tablets.
7. Mohamed. B.S et al.(2011) prepared and evaluated silymarin controlled release tablets
prepares using natural gums.
8. Shaikh.A.C et al (2011) formulated and evaluated Sustained Release Tablets Aceclofenac
using hydrophilic matrix system.
9. Deore R.K, et al (2010) perpetrated and evaluated of Sustained Release Matrix tablets
Tramadol Hydrochloride Using Glyceryl Palmitostearate.
10. Iqbal. K, et al (2012) prepared and evaluated Controlled Release Tablets Containing
Mefenamic acid.
CHAPTER III
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PRE FORMULATION
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.
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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.
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=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
TBD = Weight of the powder/tapped volume of the packing
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
repose .24 .34 .45 .45 .56 .56 .30 .45
(degree) 5 .24
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CHAPTER IV
FORMULATION
FORMULATION
Table2: of Formulation
Sr. Name of Amount (gm/tablet)
No. Ingredient
Formulation F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Code
1 Ibuprofen 200 200 200 200 200 200 200 200 200 200
CHAPTER V
EVALUATION
EVALUATION
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.
8 480 500 -4
9 510 500 2
10 510 500 2
11 510 500 2
12 515 500 3
13 520 500 4
14 480 500 -4
15 490 500 -2
16 490 500 -2
17 495 500 -1
18 480 500 -4
19 480 500 -4
20 525 500 5
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.
Table10. 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
10 F10 1.1
3. Hardness Test
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
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PFIZER TESTER
Hardness which is now more appropriately called crushing strength determinations are made
during tablet production and are used to determine the need for pressure adjustment on tablet
machine.
The strength of a tablet can be determined by breaking it between second and third fingers with
the thumb acting as a fulcrum. If there is a click sound, the tablet is deemed to have acceptance
strength.
If the tablet is too hard, it may not disintegrate in the required period of time to meet the
dissolution specifications; if it is too soft, it may not be able to withstand the handling during
subsequent processing such as coating or packaging and shipping operations.
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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.
Table12. Dissolution
S No Time minutes % Amount release Cumulative % Release
1 5 2 2
2 10 4 6
3 30 3 9
4 60 7 16
5 120 12 28
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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
absorbance of resultant solution was measured spectrophotometrically at 315nm using 0.1 N
Hydrochloric acids as blank.
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CHAPTER VI
RESULTS
DISCUSSION
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Over the past few decades, significant medical advances have been made in the area of drug
delivery with the development of controlled release dosage forms. The primary benefit of a
sustained release dosage form in comparison with conventional dosage form, maintains uniform
drug plasma concentration over an extended period of time and hence the uniform therapeutic
effect is achieved. To get a successfully sustained release product, the drug must be released
from the dosage form at a predetermined rate and dissolve in the gastrointestinal fluids
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CONCLUSION
Sustained release systems include any drug delivery system that achieves slow release of drug
over an extended period of time. If the system is successful in maintaining constant drug levels
in the blood or target tissue it is considered as controlled release system. If it is unsuccessful at
this but nevertheless extends the duration of action over that achieved by conventional delivery,
it is considered a prolonged release system. The oral route of administration for sustained release
systems has received greater attention because of more flexibility in dosage form design. The
design of oral sustained release delivery systems is subject to several inter related variables of
considerable importance such as the type of delivery system, the disease being treated, the
patient, the length of therapy and the properties of the drug.
Ibuprofen is a nonsteroidal anti-inflammatory agent used extensively in the treatment of
rheumatoid arthritis, degenerative joint disease, osteoarthritis, ankylosing spondylitis, acute
musculoskeletal disorders, and low back pain.
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