1

A PROJECT REPORT

on

FAST DISSOLVING TABLET IBUPROFEN

BACHELOR OF PHARMACY

In

NOVEL DRUG DELIVERY SYSTEM

By

AMAN TRIVEDI

B.PHARMACY

DEPARTMENT OF PHARMACY,

INVERTIS UNIVERSITY, BAREILLY-243001

BAREILLY, UTTAR PRADESH

2016-2017

ROLL NO.1310601004 ENROLLMENT NO. IU131554

2

CERTIFICATE

I hereby certify that the project work which is being presented entitled as Fast Dissolving
Tablet Ibuprofen submitted to Department of Pharmacy, Invertis university, Bareilly in
the fulfilment of the requirement for the award of degree of Bachelor of pharmacy in NDDS
embodies the original research work carried out by Aman Kumar Trivedi. This work has
been completed under my supervision and guidance. This is further stated that no part of this
project has been submitted previously either in part or full, for the award of any degree to this
or any other university.

Date:

Supervisor HOD
Dr. Ritu Gupta Ajit Kumar Yadav
Assistant Professor
Department of Pharmacy
Invertis University, Bareilly
Uttar Pradesh, India
3

Declaration

I hereby declare that the present dissertation entitled Fast Dissolving Tablet Ibuprofen an
original research work carried out by me in partial fulfilment of the requirement for the award
of degree of Bachelor of Pharmacy in NDDS from department of Pharmacy, Invertis
University, Bareilly, during the academic year 2016-2017. It is further stated that no part of
this dissertation has been submitted previously either in part or full, for the award of any
other degree by me, to this or any other University.

Date: Aman Kumar

Trivedi
Place: Bareilly (B.Pharm.)
4

ACKNOWLEDGEMENT

The only way of finding the limits of possible,

Is by going beyond them into the impossible

Arthur C. Clarke

Coming up with an idea is not difficult for anybody, but giving it a start and taking it to the
completion is a different story all together. So here I am bound to be grateful to the numerous
people who made it possible for me to give shape to the idea which I considered as my
project.

I, Aman kumar Trivedi, feel immense pleasure in praising the almighty for his grace,
guidance, strength and blessing showered on me to complete this project work as a part of B.
Pharm. Curriculam at the Department of pharmacy, Invertis village, Invertis University,
Bareilly.

In the making of this project report, I express my deepest regards to Mr. Ajit yadav, for
giving me guidance to work in the research topic.

I take pride in acknowledging the solicitous help and concern of my guide, Dr.Ritu Gupta,
Associate professor, Department of Pharmacy, Invertis University, Bareilly, for her
constant encouragement and masterly touch throughout the entire period of this work,
without which this work would not have seen the light of the day.

I extremely thankful to Mr. Shashank Chaturvedi and Jatin Jaiswal who were always there
to help me with my problems, sharing fruitful discussion, supportive cooperation and
affectionate behaviours during my project period. And I would also like to say thanks to all
5

teaching and non-teaching staff of Depart of pharmacy, Invertis University, Bareilly for
providing some common help during my project time.

It is an honor for me to have this opportunity to express my deep sense of gratitude to all my
teachers, colleagues, friends and beloved family members, who have been there all along in
this endeavour.

Finally, my efforts will remain incomplete, if I fail to acknowledge the thanks to my family
and to a very special someone,, who is giving me love, care and moral support in my life.
They were always ready to extend all possible help which give me great encouragement what
I am today is because of love, care, support and all blessing of my family members.

Thanks to all for what I am today.

Date:........................... AMAN KUMAR TRIVEDI

B.PHARM 4TH YEAR

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CONTENT

1. INTRODUCTION 8-9

1.1. ADVANTAGES OF FDDS 9-10

1.2. LIMITATIONS 10-11

1.3. METHODS OF PREPARATIONS OF FDDS 11-20

1.4. DRUG PROFILE 21-22

1.5. MECHANISM OF ACTION 22-23

2. LITERATURE REVIEW 23

3. PREFORMULATION 24

3.1. UV SPECTROSCOPY 24-25

3.2. MELTING POINT 25

3.3. LOSS ON DRYING 25

3.4. SOLUBILITY STUDY 25-26

3.5. BULK DENSITY26

3.6. TRUE DENSITY 26-27

3.7. ANGLE OF REPOSE 27

4. FORMULATION 28

4.1. MATERIAL AND METHODS 28-34

5. EVULATION 34-36

6. RESULT AND DISCUSSION 37-38

7. CONCLUSION 39

8. REFERENCE 39-40
7

1. INTRODUCTION:

Drug delivery systems (DDS) are a strategic tool for expanding markets/indications,
extending product life cycles and generating opportunities. DDS make a significant
contribution to global pharmaceutical sales through market segmentation, and are moving
rapidly. Fast dissolving drug delivery (FDDTs,) can be achieved by various conventional
methods like direct compression, wet granulation, moulding, spray drying, freeze drying,
sublimation. In order to allow fast dissolving tablets to dissolve in the mouth, they are made
of either very porous and soft- moulded matrices or compressed into tablets with very low
compression force, which makes the tablets friable and/or brittle, which are difficult to
handle, often requiring specialized peel-off blister packaging.

Many pharmaceutical dosages are administered in the form of pills, granules, powders, and
liquids. Generally, a pill design is for swallowing intact or chewing to deliver a precise
dosage of medication to patients. The pills, which include tablets and capsules, are able to
retain their shapes under Moderate pressure. However, some patients, particularly pediatric
and geriatric patients, have difficulty swallowing or chewing solid dosage forms. Many
pediatric and geriatric patients are unwilling to take these solid preparations due to a fear of
choking. In order to assist these patients, several fast-dissolving drug delivery systems have
been developed. Fast-dissolving drug delivery1 In recent years, a variety of improved
methods for delivering drugs have been developed with the aim of improving performance,
convenience and compliance

FDDTs disintegrate and/or dissolve rapidly in the saliva without the need for water. Some
tablets are designed to dissolve in saliva remarkably fast, within a few seconds, and are true
fast-dissolving tablets. Others contain agents to enhance the rate of tablet disintegration in the
oral cavity, and are more appropriately termed fast-disintegrating tablets, as they may take up
to a minute to completely disintegrate. When put on tongue, this tablet disintegrates
instantaneously, releasing the drug, which dissolves or disperses in the saliva. Some drugs are
absorbed from the mouth, pharynx and oesophagus as the saliva passes down into the
stomach. In such cases, bioavailability of drug is significantly greater than those observed
from conventional tablet dosage form.
8

The advantage of Fast Dissolving Dosage Forms are increasingly being recognized in both
industry and academia.[1]

Oral route of administration is the most convenient and preferred route of administration
among the various other delivery system. More than 70% of drugs are available in the market
in the form of oral drug delivery system due to pain avoidance and versatility but a very
elderly patient may not be able to swallow a daily dose of antidepressant. A schizophrenic
patient in the institutional setting can hide a conventional tablet under his or her tongue to
avoid their daily dose of an atypical antipsychotic. A middle aged woman undergoing
radiation therapy for breast cancer may be too nauseous to swallow her H2-blocker.Fast-
dissolving/disintegrating tablets (FDDTs) are a perfect fit for all of these patients.

A fast dissolving drug delivery system, in most cases, is a tablet that dissolves or disintegrates
in the oral cavity without the need of water or chewing these systems were first developed in
the late 1970s for the people who experience difficulties in swallowing traditional oral solid-
dosage forms. The novel technology of oral fast-dispersing dosage forms is known as fast
dissolve, rapid dissolve, rapid melt and quick disintegrating tablets . It improves drug
dissolution as well as onset of clinical effect and the pregastric absorption of drugs, which
avoids first pass hepatic metabolism to reduce the dose than those observed from
conventional dosage forms and finally, increase the bioavailability of drugs. The main
proposal of the present review is to study the practicability of fast dissolving drug delivery
and illustrate briefly the ideal properties, advantages and limitations, conventional and
patented technologies, available marketed formulations in FDTs and evaluation methods. The
Centre for Drug Evaluation and Research (CDER), US FDA defined Oral Disintegrating
Tablets (ODT) as A solid dosage form containing medicinal substances, which disintegrates
rapidly, usually within a matter of seconds, when placed upon the tongue.FDTs disintegrate
and/or dissolve instantaneously in the saliva without the use of water. Some tablets are
designed to dissolve in saliva remarkably fast, within a few seconds, and are true fast-
dissolving tablets. Others contain agents to enhance the rate of tablet disintegration in the oral
cavity, and are more appropriately termed fast-disintegrating tablets, as they may take up to a
minute to completely.[2]
 9

1.1. Advantages of Fast Dissolving Drug Delivery System FDDTs,,,,,

Fast dissolving technology offers :

Improved compliance/added convenience

No water needed

No chewing needed

Better taste

Improved stability

Suitable for controlled/sustained release actives

Allows high drug loading.

Ability to provide advantages of liquid medication in the form of solid preparation.

Adaptable and ameanable to existing processing and packaging machinery

Cost- effective.
10

Figure-1

1.2. LIMITATIONS:

The major disadvantages of FDTs is related to the mechanical strength of tablets.

FDT are very porous and soft molded metrics or compressed in a tablet with low
compression, which makes tablet friable and brittle which difficult to handle.
11

Bad tastes drugs are difficult to formulate as FDT; special precaution should have to be
taken before formulate such kind of drug.

Several FDT are hygroscopic cannot maintain physical integrity under normal condition
from humidity which requires specialized package.

Dryness of the mouth due to decreased saliva production may not be good candidates for
these tablet formulations.

Rate of absorption from the saliva solution and overall bioavailability.

Drug and dosage form stability.[1]

2. METHODS OF PREPARATION OF FDDDS:

1.3.1Conventional technologies
Various conventional manufacturing techniques for FDDDS

A.Freeze-drying or lyophilization
It is a pharmaceutical process that allows the drying of heat sensitive drugs and biological
under low temperature by the application of vacuum to remove water by sublimation. Drugs
are dissolved or dispersed in aqueous solution of a carrier, transferred to preformed blister
packs and subjected to nitrogen flush to freeze out, then placed in the refrigerator to complete
the process. Characteristics of lyophilization techniques are, they possess high porosity and
specific surface area, and gets dissolve rapidly in mouth presenting high drug bioavailability.
The major drawback of this system is high cost, time-consuming procedure and fragility,
making conventional packing inappropriate for packing this dosage form and stability issues
under stress condition.
12

Advantages
The major advantage of using this technique is that the tablets produced by this technology
have very low disintegration time and have great mouth feel due to fast melting effect.

B. Moulding method
Tablets are designed using hydrophilic ingredients, with the aim to get maximum drug
dissolution. Powder mass is wetted with hydro alcoholic solvent and compressed into a
dosage form. The solvent system is then allowed to evaporate. Taste of drug particles is
developed by spray congealing the molten mixture of hydrogenated cottonseed oil, sodium
carbonate, lecithin, poly ethene glycol with an active ingredient into lactose based tablet
triturate. Characteristics of moulding method are, very porous as solvents are removed by
drying leaving porous mass which promotes rapid dissolution.

C. Melt granulation
Melt granulation technique is a process by which the pharmaceutical powders are capably
agglomerated by a meltable binder. The benefit of this technique compared to a conventional
granulation is that no water or organic solvents is required. Since there is no drying step, the
process is less time consuming and requires less energy than wet granulation. It is a technique
useful to enhance the dissolution rate of poorly water-soluble drugs, such as griseofulvin.

D. Mass-extrusion
In this the mixed ingredients are softened by water soluble ingredient i.e. polyethene glycol,
using methanol as solvent, passing through an extruder to form thin cylinders. Which further
get sliced with a heated blade to form small tablets. Characteristics of this method is these
products can be used to mask bitter tasting drugs making small granu
les thus enhancing oral bioavailability.

E. Sublimation
Rapid disintegration and dissolution is acquired by formulating into porous mass by
incorporating inert solid ingredients that volatilize rapidly like urea, camphor ammonium
carbonate, ammonium bicarbonate and hexamethylene-tetramine. They were mixed with
other ingredients and compressed. The volatile material is evolved by reduced pressure and
applying slight temperature leaving the mass in porous form. Characteristics of sublimation
method are, they are porous in nature, solvents like cyclohexane and benzene can be used.
13

Figure-2: Schematic diagram of sublimation techniques for preparing fast dissolving

tablets

F. Direct compression
The disintegrant addition technology (direct compression) is the most preferred technique to
manufacture the tablets due to certain advantages:
High doses can be accommodated and final weight of the tablet can exceed that of other
methods.
The easiest way to manufacture the tablets.
Conventional equipment and commonly available excipients are used.
A limited no. of processing steps are involved.
Cost effectiveness.
Tablet size and hardness strongly affect the disintegrant efficacy. Hard and large tablets have
more disintegration time than normally required. Very soft and small tablets have low
mechanical strength. So, an optimum kind and concentration of disintegrant should be chosen
to achieve quick disintegration and high dissolution rates. Above the critical concentration
level, however, disintegration time remains approximately constant or even increases.
14

Fig: Process of direct compression

Table : Ideal requirements, advantages and limitations of direct compression

S. No. Ideal requirements Advantages Limitations
1. Flowability Cost effective production Segregation
2. Compressibility Better stability of API Variation in functionality
3. Dilution Potential Faster dissolution Low dilution potential
4. Reworkability Less wear and tear of punches Reworkability
5. Stability Simple validation Poor compressibility of API
6. Controlled Particle Size Low microbial contamination Lubricant sensitivity

G. Cotton candy process

This process is so named as it utilises a unique spinning mechanism to produce a floss-like
crystalline structure, which mimics cotton candy. Cotton candy process involves the
formation of Matrix of polysaccharides or saccharides by the simultaneous action of flash
melting and spinning. The matrix formed is partially recrystallized to have improved flow
properties and compressibility. This candy floss matrix is then milled and blended with active
ingredients and excipients and subsequently compressed to FDTs.
However, other polysaccharides such as poly maltodextrins and polydextrose can be
transformed into fibers at 30-40% lower temperature than sucrose. This modification permits
the safe incorporation of thermolabile drugs into the formulation. The tablets manufactured
by this process are highly porous in nature and offer very pleasant mouth feel due to fast
solubilization of sugars in the presence of saliva.

H. Spray-drying
By this method, ingredients are integrated by hydrolyzed and nonhydrolyzed gelatins as
supporting agents, mannitol as bulking agent, sodium starch glycolate or crosscarmellose
sodium as disintegrating and an acidic material (e. g. citric acid) and or alkali material (e. g.
sodium bicarbonate) to enhance disintegration and dissolution. Characteristics of the spray-
drying method is this method gives rapid dissolution (within 20 seconds) when dosage form
gets in contact with the aqueous medium.

I. Phase transition process

15

This processes for the disintegration of FDTs by phase transition of sugar alcohols using
erythritol (melting point 122 C), xylitol (93-95 C), trehalose (97 C), and mannitol (166
C). Tablets were produced by compressing a powder containing two sugar alcohols with
high and low melting points and subsequent heating at a temperature between their melting
points. Before the heating process, the tablets do not have sufficient hardness because of low
compatibility.
The tablet hardness was increased after heating, due to the increase of interparticle bonds or
the bonding surface area in tablets induced by phase transition of lower melting point sugar
alcohol.

Figure-3
Fig: Flow chart for coating liquid and solid particles using spray-drying process
J. Nanoionization
A recently developed nanomelt technology involves a reduction in the particle size of the
drug to nano size by milling the drug using a proprietary wet-milling technique. The
nanocrystals of the drug are stabilized against agglomeration by surface adsorption on
selected stabilizers, which are then incorporated into MDTs. This technique is especially
advantageous for poorly water soluble drugs. Other advantages of this technology include
fast disintegration/dissolution of nanoparticles leading to increased absorption and hence
higher bioavailability and reduction in dose, cost effective manufacturing process,
16

conventional packaging due to exceptional durability and a wide range of doses (up to 200
mg drug per unit).

K. Oral disintegrating or fast dissolving thin films

It is a new frontier in immediate release tablet that provides a very convenient means of
taking medications and supplements. In this technique, a non-aqueous solution is prepared
containing water soluble film forming polymer (pullulan, carboxymethylcellulose,
hydroxypropyl methyl cellulose, hydroxyl ethyl cellulose, hydroxyl propyl cellulose,
polyvinyl pyrrolidone, polyvinyl alcohol or sodium alginate, etc.), drug and other taste
masking ingredients, which is allowed to form a film after evaporation of solvent. In the case
of a bitter drug, resin adsorbate or coated microparticles of the drug can be incorporated into
the film. This film, when placed in the mouth, melts or dissolves rapidly, releasing the drug in
solution or suspension form. The features of this system include paper-thin films of size less
than 22 inches, dissolution in 5 sec, instant drug delivery and flavoured aftertaste.

1.3.2 Patented technologies for fast dissolving tablets

Rapid-dissolving characteristic of FDTs is generally attributed to fast penetration of water
into tablet matrix resulting in its fast disintegration. Several technologies have been
developed on the basis of formulation aspects and different processes and patented by several
pharmaceutical companies. Patented technology is described below:

1.3.3 Zydis technology

Zydis formulation is a unique freeze-dried tablet in which drug is physically entrapped or
dissolved within the matrix of fast dissolving carrier material. When zydis units are put into
the mouth, the freeze-dried structure disintegrates instantaneously and does not require water
to aid swallowing. The zydis matrix is composed of many materials designed to achieve a
number of objectives. To impart strength and resilience during handling, polymers such as
gelatin, dextran or alginates are incorporated. These form a glossy amorphous structure,
which imparts strength.

Limitations
The amount of drug could be incorporated should generally be less than 400 mg for
insoluble drugs and less that 60 mg for soluble drugs.
17

The particle size of the insoluble drugs should not be less than 50 m and not more than 200
m to prevent sedimentation during processing.

Advantages
Buccal pharyngeal and gastric regions are all areas of absorption from this formulation. Any
pre-gastric absorption avoids first-pass metabolism and can be an advantage in drugs that
undergo a great deal of hepatic metabolism.
The Zydis formulation self-preserving because the final water concentration in the freeze-
dried product is too low to allow for microbial growth.
Patients who have difficulty swallowing oral medication due to dysphagia, stroke or
medical conditions such as gastro esophageal reflux disease, multiple sclerosis or Parkinsons
disease.

Disadvantages
The process of freeze-drying is a relatively expensive manufacturing process.
The formulation is very lightweight and fragile, and therefore should not be stored in
backpacks or the bottom of purses.
It has poor stability at higher temperatures and humidities.
A water insoluble drug can be incorporated only up to 400 mg per tablet or less. On the
other hand water, the soluble drug can be incorporated only up to 60 mg.

1.3.4 Orasolv technology

Orasolv technology has been developed by CIMA labs. In this system, the active medicament
is taste masked. It also contains the effervescent disintegrating agent. Tablets are made by
direct compression technique at low compression force in order to minimise oral dissolution
time. Conventional blenders and tablet machine is used to produce the tablets. The tablets
produced are soft and friable and packaged in specially designed pick and place system.

Advantages
Taste-masking is two-fold, quick dissolution. This technology has been used for drug
strengths in the range of 1 mg to 750 mg. Depending on formulation and tablet size, the
disintegration time of the tablet can be designed in the range of 10 to 40 seconds.
18

Disadvantages
They are sensitive to moisture due to the presence of the effervescent system and must be
packaged appropriately. Low mechanical strength.

1.3.5 Durasolv technology

Dura
solv is the patented technology of CIMA labs. The tablets made by this technology consist of
a drug, fillers and lubricant. Tablets are prepared by using conventional tableting equipment
and have good rigidity. These can be packed into conventional packaging system like blisters.
Durasolv is an appropriate technology for products requiring low amounts of active
ingredients.

Advantages
DuraSolv technology is good for tablets having a low amount (125 mcg to 500 mg) of active
ingredients and tablets are compressed to a greater hardness of 15-100 N, resulting in a more
durable ODT. As a result, this technology enables packaging flexibility; tablets can be bottled
and blistered.

Disadvantages
The technology is not compatible with larger doses of active ingredients because the
formulation is subjected to high pressure during compaction. The drug powder coating in
Durasolv may become fractured during compaction, exposing the bitter tasting drugs to the
patient taste buds.

1.3.6 Wow tab technology

Wow, tab technology is patented by Yamanouchi Pharmaceutical Co. WOW means Without
Water. In this process, a combination of low moldability saccharides and high moldability
saccharides is used to obtain a rapidly melting strong tablet. The combination of high and low
moldability is used to produce tablets of adequate hardness.

Advantages
Adequate dissolution rate and hardness. Wow, tab product can be packed in both into the
conventional bottle and blister packs.
19

Disadvantages
No significant change in bioavailability.

1.3.7 Flash dose technology

Flash dose technology has been patented by Fuisz. Nurofen melt let, a new form of Ibuprofen
as melt-in-mouth tablets, prepared using flash dose technology is the first commercial
product launched by Biovail Corporation. Flash dose tablets consist of self-binding shear
form matrix termed as floss. Shearform matrices are prepared by flash heat processing.

Advantages
High surface area for dissolution

Disadvantage
High temperature required to melt the matrix can limit the use of heat-sensitive drugs,
sensitive to moisture and humidity.
The dosage form can accommodate only up to 600 mg of drug.
Tablets produced are highly friable, soft and moisture sensitive. Therefore specialised
packing is required.

1.3.8 Flashtab technology

The flashtab technology is yet another fast-dissolving/disintegrating tablet formulation.
Prographarm laboratories have patented the flashtab technology. It utilizes most of the same
excipients as in conventional compressed tablets. A disintegrating agent and a swelling agent
are used in combination with coated drug particles in this formulation to produce a tablet that
disintegrates in the mouth in less than one minute.

1.3.9 Oraquick technology

K. V. S. Pharmaceuticals have a patent over this technology. It utilizes taste masking
microsphere technology called as micromask, which provides superior mouth feel over taste
masking alternatives, significant mechanical strength, and quick disintegration/ dissolution of
20

the product. Any kind of solvents are not utilized by taste masking process. Therefore it leads
to superior and fast efficient production.

Advantages
Faster and efficient production, appropriate for heat-sensitive drugs

1.3.10 Dispersible tablet technology

Lek in Yugoslavia was issued patents for dispersible tablets of dihydroergotoxine and
cimetidine, which were claimed to disintegrate in less than 1 minute when in contact with
water at room temperature. Dihydroergotoxine is poorly soluble in water in the free base
form. An improved dissolution rate of dihydroergotoxine methanesulphonate was observed
with dispersible tablets containing 0.8-10%, preferably about 4% by weight, of organic acids.
One of the essential excipients in the cimetidine formulate ion a disintegrating agent. It
provides rapid swelling and/or good wetting capability to the tablets and thereby a quick
disintegration. The disintegrating agents include starch or modified starches, microcrystalline
cellulose, alginic acid, crosslinked sodium carboxymethylcellulose, and cyclodextrin
polymers. A combination of two or more disintegrating agents produced better disintegration
results.

1.3.11 Advatab technology

Advatab tablets disintegrate rapidly in the mouth, typically in less than 30 seconds, to allow
for convenient oral drug administration without water. These tablets are especially suited to
those patients that experience difficulty in swallowing capsules and tablets. Advatab is
distinct from other FDT technologies as it can be combined with Eurands complimentary
particle technologies like its world leading Microcaps taste masking technology and its
Diffucaps, controlled release technology.

1.3.12 Nanocrystal technology

For fast dissolving tablets, elan's proprietary nanocrystal technology can enable formulation
and improve compound activity and final product characteristics. Decreasing particle size
increases the surface area, which leads to an increase in dissolution rate. This can be
accomplished predictably and efficiently using nanocrystal technology. Nanocrystal particles
21

are small particles of drug substance, typically less than 1000 nanometers (nm) in diameter,
which are produced by milling the drug substance using a proprietary wet milling technique.

Nanocrystal fast dissolving technology provides for

Pharmacokinetic benefits of orally administered nanoparticles (<2 microns) in the form of a
rapidly disintegrating tablet matrix.
Product differentiation based upon a combination of proprietary and patent protected
technology elements.
Cost-effective manufacturing processes that utilize conventional, scalable unit operations.

1.3.13 Pharmabust technology

Pharmaburst technology is being patented by SPI pharma. The tablet manufactured by this
process involves a dry blend of a drug, flavors, and lubricant then followed by compression
into tablets which then dissolve within 30-40 seconds. Tablets manufactured by this
methodology have sufficient strength can be packed in blister packs and bottles.

Frosta technology (Akina)

This technology is patented by Akina. Frosta technology utilizes the core concept of
formulating plastic granules and compressing at low pressure to produce strong tablets with
high porosity. The process involves mixing the porous plastic material with water penetration
enhancer and followed by granulating with a binder.[3]

1.4. DRUG PROFILE

Ibuprofen is a medication in the nonsteroidal anti-inflammatory drug (NSAID) class that is

used for treating pain, fever, and inflammation. This includes painful menstrual
periods, migraines, and rheumatoid arthritis. It comes under the propionic acid derivatives of
the non-selective COX inhibitor class of nonsteroidal anti-inflammatory drug (NSAID) class.

1.4.1DESCRIPTION:
22

About 60% of people improve with any given NSAID, and it is recommended that if one
does not work then another should be tried. It may also be used to close a patent ductus
arteriosus in a premature baby. It can be used by mouth or intravenously. It typically begins
working within an hour.

Common side effects include heartburn and a rash. Compared to other NSAIDs it may have
fewer side effects such as gastrointestinal bleeding. It increases the risk of heart
failure, kidney failure, and liver failure. At low doses, it does not appear to increase the risk
of myocardial infarction; however, at higher doses it may. Ibuprofen can also result in
worsened asthma. While it is unclear if it is safe in early pregnancy, it appears to be harmful
in later pregnancy and therefore is not recommended. Like other NSAIDs, it works by
inhibiting the production of prostaglandins by decreasing the activity of the
enzyme cyclooxygenase. Ibuprofen might be a weaker anti-inflammatory than other NSAIDs.

Ibuprofen was discovered in 1961 by Stewart Adams and marketed as Brufen. It is available
under a number of trade names, including Advil and Motrin. It was first marketed in 1969 in
the United Kingdom and in the United States in 1974. It is on the World Health Organization's
List of Essential Medicines, the most effective and safe medicines needed in a health system.
It is available as a generic medication. The wholesale cost in the developing world is between
0.01 and 0.04 USD per dose. In the United States it costs about 0.05 USD per dose.[4]

1.4.2 CHEMICAL NAME:

Iso butyl phenyl propionic acid

1.4.3 STRUCTURE:
23

HO

isobutylphenylpropionic acid

1.4.4 MOLECULAR FORMULA- C13H18O2

1.4.5 MOLECULAR WEIGHT- 206.2808

1.4.6 BOILING POINT- 668.35 [K]

1.4.7MELTING POINT- 392.79 [K]

1.4.8 BIO- AVAILABILITY:

87100% (oral), 87% (rectal)

1.4.9 VOLUME OF DISTRIBUTION:

Ibuprofen, like most drugs of its class, is highly protein bound (>99% bound at 20 g/mL).
Protein binding is saturable and at concentrations >20 g/mL binding is non-linear. Based on
24

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. The clinical significance of these findings
is unknown.

1.4.10 T-HALF LIFE (1/2):

1.3 to 3 hours.

DOSE:

Dose 200mg 10mg/kg in Febrile

(2.8mg/kg) in Children
Adults

1.4.11MECHANISM OF ACTION:

Ibuprofen is a non-selective inhibitor of an enzyme called cyclooxygenase (COX), which is

required for the synthesis of prostaglandins via the arachidonic acid pathway. COX is needed
to convert arachidonic acid to prostaglandin H2 (PGH2) in the body. This PGH2 is then
converted to prostaglandins. The inhibition of COX by ibuprofen therefore lowers the level of
prostaglandins made by the body.

The prostaglandins that are formed from PGH2 are important mediators of sensations such as
pain and processes such as fever and inflammation. The antipyretic effects may arise as a
result of action on the hypothalamus leading to vasodilation, an increased peripheral blood
flow and subsequent heat dissipation.

Anticoagulant effects are also mediated through inhibition of COX, which converts
arachidonic acid into thromboxane A2, a vital component in platelet aggregation that leads to
the formation of blood clots.

There are two forms of COX in the body - COX-1 and COX-2. The pain and inflammation
reducing effects of NSAIDs are mediated through the inhibition of COX-2, while COX-1
25

inhibition blocks the formation of thromboxane. The long-term blockage of COX-1 with
chronic use of NSAID, however, may cause gastric toxicity, as COX-1 usually maintains the
gastric mucosa.

CHAPTER-2

2.1. LITERATURE REVIEW

1. Mishra .K.S et al (2013) formulated and evaluated rapidly disintegrated tablet of

ibuprofen.[6]

2. Chandrika .M.B et al (2016) formulated and evaluated rapidly disintegrated tablet of

ibuprofen tablets by using different super disintegrating agents.[7]

3. Mali P.A et al (2012) formulated and evaluated fast dissolving tablet carbamazepine.[8]

4. Newa Madhuri et al (2008) prepared and evaluated fast dissolving Ibuprofen-

polyethylene glycol 6000 solid dispersion.[8]

5. Vaishali .Y. Londhe et al (2012) formulated and evaluated fast dissolving film of
Telmisartan.[9]

6. Basu Biswajit et al (2011) formulated and evaluated fast dissolving tablet of Cinnarizine
using super disintegrant blends and subliming material.[10]

7. Sharma Deepak et al (2015) formulated and evaluated fast disintegrating tablet

Salbutamol sulphate, Cetrizine hydrochloride in combined pharmaceutical doses form: A new
era in novel drug delivery for Pediatrics and Geriatrics.[11]

8. Gupta Sparsh et al (2015) Novel study in fast dissolving drug delivery system : A review.
[12]

9. Turnen Elina et al (2014) cyclodextrin in fast dissolving drug formulation for intraoral
administration.[13]
26

10. Parmar Dipika et al (2012) reported as Orally fast dissolving films as dominant dosage
form for quick release.[14]

3. PREFORMULATION:

Preformulation testing is the first step in the rational development of dosage forms. It can
be defined as an investigation of physical and chemical property of a drug substance alone
and when combined with excipients.

It can be defined as th e studies and investigation of physical and chemical properties of the
drug substance alone and when combined with exeipients.

utilizes biopharmaceutical principles in the determination of physicochemical

properties of the drug substance.

Prior to the development of any dosage form new drug , Preformulation is branch of
Pharmaceutical science that it is essential that certain fundamental physical &
chemical properties of drug powder are determined .

This information may dictate many of subsequent event & approaches in formulation
development.

This first learning phase is called as preformulation.

3.1 UV SPECTROSCOPY:

In the UV study, the spectra of pure drug and the dispersed drug are scanned.
27

e.g. The spectrum of the dispersed beta carotene resembles that betacarotene is
dissolved in organic solvents but do not indicate the molecular dispersion of drug in
polymer.

It is the branch of science that deals with the study of interaction of matter with light.

OR

It is the branch of science that deals with the study of interaction of electromagnetic
radiation with matter.

Principles of Spectroscopy:

1. Absorption Spectroscopy:

An analytical technique which concerns with the measurement of absorption of

electromagnetic radiation.

e.g. UV (200 - 400 nm) / Visible (400 - 800 nm) Spectroscopy

2. Emission Spectroscopy:

An analytical technique in which emission (of a particle or radiation) is dispersed

according to some property of the emission & the amount of dispersion is measured.

e.g. Mass Spectroscopy

28

f(x) = 12
R = 0

10

absorbanceT 6

0
0 2 4 6 8 10 12

concentration

Fig UV Curve

3.2 MELTING POINT:

The melting point (or, rarely, liquefaction point) of a solid is the temperature at which it
changes state from solid to liquid at atmospheric pressure. At the melting point the solid and
liquid phase exist in equilibrium. The melting point of a substance depends on pressure and is
usually specified at standard pressure. When considered as the temperature of the reverse
change from liquid to solid, it is referred to as the freezing point or crystallization point.
Because of the ability of some substances to supercool, the freezing point is not considered as
a characteristic property of a substance. When the "characteristic freezing point" of a
substance is determined, in fact the actual methodology is almost always "the principle of
observing the disappearance rather than the formation of ice", that is, the melting point.
29

3.3 Loss on Drying (LOD)

Loss on drying is a widely used test method to determine the moisture content of a sample,
although occasionally it may refer to the loss of any volatile matter from the sample. Loss in
drying does not usually refer to molecularly bound water or water of crystallisation.

3.4 Solubility studies of water and buffers

Solubility is a chemical property referring to the ability for a given substance, the solute, to
dissolve in a solvent.

It is measured in terms of the maximum amount of solute dissolved in a solvent at

equilibrium.

The resulting solution is called a saturated solution.

Certain substances are soluble in all proportions with a given solvent, such as ethanol in
water.

This property is known as miscibility.

Under various conditions, the equilibrium solubility can be exceeded to give a so-called
supersaturated solution, which is metastable.

The solvent is often a solid, which can be a pure substance or a mixture.

The species that dissolves, the solute, can be a gas, another liquid, or a solid.

Solubilities range widely, from infinitely soluble such as ethanol in water, to poorly soluble,
such as silver chloride in water.

The term insoluble is often applied to poorly soluble compounds, though strictly speaking
there are very few cases where there is absolutely no material dissolved.
30

The process of dissolving, called dissolution, is relatively straightforward for covalent

substances such as ethanol.

When ethanol dissolves in water, the ethanol molecules remain intact but form new hydrogen
bonds with the water.

When, however, an ionic compound such as sodium chloride (NaCl) dissolves in water, the
sodium chloride lattice dissociates into separate ions which are solvated (wrapped) with a
coating of water molecules.

Nonetheless, NaCl is said to dissolve in water, because evaporation of the solvent returns
crystalline NaCl.

3.5 BULK DENSITY:

The bulk density of a powder is the ratio of the mass of an untapped powder sample and its
volume including the contribution of the interparticulate void volume. Hence, the bulk
density depends on both the density of powder particles and the spatial arrangement of
particles in the powder bed. The bulk density is expressed in grams per millilitre (g/ml)
although the international unit is kilogram per cubic metre (1 g/ml = 1000 kg/m3 ) because
the measurements are made using cylinders. It may also be expressed in grams per cubic
centimetre (g/cm3 ).

3.6 TRUE DENSITY:

The particle density or true density of a particulate solid or powder, is the density of the
particles that make up the powder, in contrast to the bulk density, which measures the average
density of a large volume of the powder in a specific medium (usually air).

The particle density is a relatively well-defined quantity, as it is not dependent on the degree
of compaction of the solid, whereas the bulk density has different values depending on
31

whether it is measured in the freely settled or compacted state (tap density). However, a
variety of definitions of particle density are available, which differ in terms of whether pores
are included in the particle volume, and whether voids are included.

3.7 ANGLE OF REPOSE:

The angle of repose, or critical angle of repose of a granular material is the steepest angle of
descent or dip relative to the horizontal plane to which a material can be piled without
slumping. At this angle, the material on the slope face is on the verge of sliding. The angle of
repose can range from 0 to 90. The morphology of the material affects the angle of repose;
smooth, rounded sand grains cannot be piled as steeply as can rough, interlocking sands. The
angle of repose can also be affected by additions of solvents; if a small amount of water is
able to bridge the gaps between particles, electrostatic attraction of the water to mineral
surfaces will increase the angle of repose, and related quantities such as the soil strength.

When bulk granular materials are poured onto a horizontal surface, a conical pile will form.
The internal angle between the surface of the pile and the horizontal surface is known as the
angle of repose and is related to the density, surface area and shapes of the particles, and
the coefficient of friction of the material. Material with a low angle of repose forms flatter
piles than material with a high angle of repose.

The term has a related usage in mechanics, where it refers to the maximum angle at which an
object can rest on an inclined plane without sliding down. This angle is equal to
the arctangent of the coefficient of static friction s between the surfaces.
32

4. FORMULATION:

Materials and Methods

Ibuprofen was obtained from Natco Pharma ,Hyderabad, India. Sodium starch glycolate,
crosspovidone, Croscarmellose sodium, Mannitol, Micro crystalline cellulose, talc and
magnesium stearate were purchased . All other materials used were of analytical grade.

Preparation of fast dissolving tablets

The compositions of the tablets are given in Table 1. All the ingredients as shown in Table
1 were passed through mess80, co-ground in a motor and pestle. Then talc and magnesium
stearate were added and mixed for 10 minutes. To study the influence of concentration of the
sodium starch glycolate on the performance of Ibuprofen, a set of four formulations (F 1, F2,
F3, F4) were prepared using four different concentrations of sodium starch glycolate viz, 2%,
3%, 4% & 5%w/w respectively. To study the influence of various superdisintegrants on the
performance of Ibuprofen, a set of three formulations (F 4, F5 and F6) were prepared using
three different superdisintegrants viz, Sodium starch glycolate(5%), Croscarmellose
sodium(5%), Crospovidone (5%) respectively. The powder blend was compressed into tablets
on a rotary multi-station tabletting machine (Cadmach Machinery Co. Pvt. Ltd., Mumbai)
using 7 mm round and flat punches. Tablets were stored in airtight container and used for
further study.

Evaluation of formulated tablets

The prepared tablets were evaluated for the following parameters.

Hardness test [8]

The compression force required to break the tablet in to two halves was measured by using
Monsanto hardness tester.
33

Weight variation [9]

Weight variation test is done with 20 tablets. It is the individual variation of tablet weight
from the average weight of 20 tablets.

Friability [10]

Roche friabilator was used to determine the friability. Pre weighed tablets were placed in
friabilator and rotated at a speed of 25 rpm for 4 minutes or up to 100 revolutions. The tablets
are dropped from a distance of 6 inches in each revolution. The tablets were then reweighed
after removal of fines and the percentage of weight loss was calculated.

Content uniformity [11]

Twenty tablets were powdered, and powder equivalent to 100 mg of Ibuprofen was accurately
weighed and transferred into a 100 ml volumetric flask. Initially, 5 ml methanol was added
and shaken for 10 min. Then, the volume was made up to 100 ml with 6.8 phosphate buffer.
The solution was filtered, diluted suitably and analyzed spectrophotometrically at 221 nm.

Wetting time and water absorption ratio [12,13]

A piece of paper folded twice was kept in a Petri dish containing 6 ml of purified water
containing amaranth dye. A tablet was placed on the tissue paper. The time required to
develop a colour on the upper surface of the tablet was recorded as the wetting time. The
same procedure was followed for determining the water absorption ratio(R) and was
determined according to the following equation.

R = [(Wa Wb)/Wb ] 100

Where, Wb and Wa were the weights of the tablet before and after water absorption.

In vitro dispersion time [14]

Tablet was added to 10 ml of phosphate buffer solution pH 6.8 (pH of saliva) at 37+ 0.5C.
Time required for complete dispersion of tablet was measured.
34

Disintegration test [15]

The disintegration time for all formulations was carried out using tablet disintegration test
apparatus. Six tablets were placed individually in each tube of disintegration test apparatus.
The water was maintained at a temperature of 372C and time taken for the entire tablet to
disintegrate completely was noted.

Fineness of dispersion [16]

This test is performed by placing two tablets in 100 ml of water and stirring it gently, till the
tablets get completely disintegrated. The formulation is considered to form a smooth
dispersion if the complete dispersion passes through a sieve screen with a nominal mesh
aperture of 710 m without leaving a residue on the mesh.

In vitro dissolution studies [17]

In vitro dissolution studies are performed by using USP dissolution test apparatus using 6.8
phosphate buffer as dissolution medium. The paddles are allowed to rotate at speed of 100
rpm. The dissolution medium was maintained at a temperature of 37+0.5 C and samples are
withdrawn at an interval of every 5 min. The volume of the withdrawn samples is replaced by
fresh dissolution medium in order to keep the volume of the dissolution medium as constant.
The withdrawn samples were filtered and absorbance was measured at absorption maxima of
221nm using UV-visible spectrophotometer.

Table.Dissolution

S No Time minutes % Amount release Cumulative % Amount Release

1 5 0 1
2 10 5 4
3 20 9 6
4 30 10 9
5
35

DISSOLUTION
120

100

80

cumulative% DRUG RELEASE 60

40

20

0
0 1 2 3 4 5 6 7

TIME ( IN MIN)

METHODS:

Tablet: Manufacturing methods/Direct compression

36

Introduction
In early days, most of the tablets require granulation of the powdered Active Pharmaceutical
Ingredient (API) and Excipients. At the availability of new excipients or modified form of old
excipients and the invention of new tablet machinery or modification of old tablet machinery
provides an ease in manufacturing of tablets by simple procedure of direct compression.
Amongst the techniques used to prepare tablets, direct compression is the most advanced
technology. It involves only blending and compression. Thus offering advantage particularly
in terms of speedy production. Because it requires fewer unit operations, less machinery,
reduced number of personnel and considerably less processing time along with increased
product stability.

Definition:

The term direct compression is defined as the process by which tablets are compressed
directly from powder mixture of API and suitable excipients. No pre-treatment of the powder
blend by wet or dry granulation procedure is required.

The events that motivates the industry people to use direct compression technique
I. Commercial availability of the directly compressible excipients possessing both
good compressibility and good flow ability.
For example, Spray dried lactose, Anhydrous lactose, Starch-1500,
microcrystalline cellulose, Di-Pac , Sorbitol
II. Major advances in tablet compression machinery,
i) Improved positive die feeding
ii) Pre compression of powder blend

Merits

i)Direct compression is more efficient and economical process as compared to other

processes, because it involves only dry blending and compaction of API and necessary
excipients.
ii)The most important advantage of direct compression is economical process.Reduced
processing time, reduced labor costs, fewer manufacturing steps, and less number of
equipments are required, less process validation, reduced consumption of power.
iii)Elimination of heat and moisture, thus increasing not only the stability but also the
suitability of the process for thermolabile and moisture sensitive APIs.
iv)Particle size uniformity.
v)Prime particle dissolution.
37

In case of directly compressed tablets after disintegration, each primary drug particle is
liberated. While in the case of tablets prepared by compression of granules, small drug
particles with a larger surface area adhere together into larger agglomerates; thus decreasing
the surface area available for dissolution.
vi)The chances of batch-to-batch variation are negligible, because the unit operations
required for manufacturing processes is fewer.
vii)Chemical stability problems for API and excipient would be avoided.
viii)Provides stability against the effect of aging which affects the dissolution rates.

Merits over wet granulation process

The variables faced in the processing of the granules can lead to significant tableting
problems. Properties of granules formed can be affected by viscosity of granulating solution,
the rate of addition of granulating solution, type of mixer used and duration of mixing,
method and rate of dry and wet blending. The above variables can change the density and the
particle size of the resulting granules and may have a major influence on fill weight and
compaction qualities. Drying can lead to unblending as soluble API migrates to the surface of
the drying granules.

Excipient Related
i)Problems in the uniform distribution of low dose drugs.
ii)High dose drugs having high bulk volume, poor compressibility and poor flowability are
not suitable for direct compression. For example, Aluminium Hydroxide, Magnesium
Hydroxide
iii)The choice of excipients for direct compression is extremely critical. Direct compression
diluents and binders must possess both good compressibility and good flowability.
iv)Many active ingredients are not compressible either in crystalline or amorphous forms.
v)Direct compression blends may lead to unblending because of difference in particle size or
density of drug and excipients. Similarly the lack of moisture may give rise to static charges,
which may lead to unblending.
vi)Non-uniform distribution of colour, especially in tablets of deep colours.

Process Related
i)Capping, lamination, splitting, or layering of tablets is sometimes related to air entrapment
during direct compression. When air is trapped, the resulting tablets expand when the
pressure of tablet is released, resulting in splits or layers in the tablet.
ii)In some cases require greater sophistication in blending and compression equipments.
iii)Direct compression equipments are expensive.

Manufacturing steps for direct compression

38

Direct compression involves comparatively few steps:

i)Milling of drug and excipients.
ii)Mixing of drug and excipients.
iii)Tablet compression.

Direct compression Excipients

Direct compression excipients mainly include diluents, binders and disintegrants. Generally
these are common materials that have been modified during the chemical manufacturing
process, in such a way to improve compressibility and flowability of the material. The
physicochemical properties of the ingredients such as particle size, flowability and moisture
are critical in direct compression tableting. The success of direct compression formulation is
highly dependent on functional behavior of excipients.

An ideal direct compression excipient should possess the following

attributes

i) It should have good compressibility.

ii) It should possess good hardness after compression, that is material should not possess any
deformational properties; otherwise this may lead to capping and lamination of tablets.
iii) It should have good flowability.
iv) It should be physiologically inert.
v) It should be compatible with wide range of API.
vi) It should be stable to various environmental conditions (air, moisture, heat, etc.).
vii) It should not show any physical or chemical change in its properties on aging.
viii) It should have high dilution potential. i.e. Able to incorporate high amount of API.
ix) It should be colourless, odorless and tasteless.
x) It should accept colourants uniformity.
xi) It should possess suitable organoleptic properties according to formulation type, that is in
case of chewable tablet diluent should have suitable taste and flavor. For example mannitol
produces cooling sensation in mouth and also sweet test.
xii) It should not interfere with bioavailability and biological activity of active ingredients.
xiii) It should be easily available and economical in cost.

Major excipients required in direct compression

I.Diluents
II.Binders
III.Disintegrants
39

Diluents
Selection of direct compression diluent is extremely critical, because the success or failure of
direct compression formulation completely depends on characteristics of diluents. There are
number of factors playing key role in selection of optimum diluent. Factors like- Primary
properties of API (particle size and shape, bulk density, solubility), the characteristics needed
for processing (flowability, compressibity), and factors affecting stability (moisture, light, and
other environmental factors), economical approach and availability of material. After all, one
can say that raw material specifications should be framed in such a way that they provide an
ease in manufacturing procedures and reduce chances of batch to batch variation. This
becomes possible only when the raw material specifications reflect most of properties of
diluents as mentioned in section 1.5.

Binders

Binders are the agents used to impart cohesive qualities to the powdered material. The quality
of binder used has considerable influence on the characteristic of the direct compression
tablets. The direct compression method for preparing tablets requires materials which are not
only free flowing but also sufficiently cohesive to act as binder.

5. EVALUATION:

5.1 HARDNESS:

Tablet hardness testing, is a laboratory technique used by the pharmaceutical industry

to test the breaking point and structural integrity of a tablet"under conditions of storage,
transportation, and handling before usage" The breaking point of a tabletis based on its
shape.

5.2 WEIGHT VARATION:

Uniformity of Content is a pharmaceutical analysis parameter for the quality control

of capsules or tablets. Multiple capsules or tablets are selected at random and a suitable
analytical method is applied to assay the individual content of the active ingredient in each
capsule or tablet.

The preparation complies if not more than one (all within limits) individual content is outside
the limits of 85 to 115% of the average content and none is outside the limits of 75 to 125%
40

of the average content. The preparation fails to comply with the test if more than 3 individual
contents are outside the limits of 85 to 115% of the average content or if one or more
individual contents are outside the limits of 75% to 125% of the average content

5.3 FRABILITY:

Roche friabilator was used to determine the friability. Pre weighed tablets were placed in
friabilator and rotated at a speed of 25 rpm for 4 minutes or up to 100 revolutions. The tablets
are dropped from a distance of 6 inches in each revolution. The tablets were then reweighed
after removal of fines and the percentage of weight loss was calculated.

The friability of the tablets was measured in a Roche friabilator (Camp-bell Electronics,
Mumbai). Tablets of a known weight (W0) or sample 10 tablets are dedusted in a drum for a
fixed time (100 revolutions) and weighed (W) again. Percentage friability was calculated
from the loss in weight as given in the equation as below. The weight loss should not be more
than 1%

Percentagefriability=Initialweight(W0)Finalweight(W)/Initialweight(W0)100.
41

5.4 Disintegration test

The disintegration time for all formulations was carried out using tablet disintegration test
apparatus. Six tablets were placed individually in each tube of disintegration test apparatus.
The water was maintained at a temperature of 372C and time taken for the entire tablet to
disintegrate completely was noted.

5.5 DRUG CONTENT:

Twenty tablets were powdered and powder equivalent tp 100 mg of Ibuprofen was accurately
weighed and transferred into 100 mg volumetric flask. Initially, 5 ml methanol was added and
shaken for 10 min. Then, the volume was made up to 100 ml with 6.8 phosphate buffer. The
solution in the volumetric flask was filtered, diluted suitably and analyzed
spectrophotometrically at 221 nm.

5.6 WETTING TIME:

The wetting time of the tablets can be measured using a simple procedure. Five circular tissue
papers of 10 cm diameter are placed in a petridish with a 10 cm diameter. 10 ml of water
containing amaranth a water soluble dye is added to petridish. A table is carefully placed on
the surface of the tissue paper. The time required for required for water to reach upper surface
of the tablet is noted as a wetting time.

INVITRO DISPERSION TIME:

Tablets was added to 10 ml of phosphate buffer solution pH 6.8 (pH of saliva) at 370.5C.
Time required for complete dispersion of tablet was measured.

5.7 In Vitro Dissolution Study

In vitro dissolution studies for all the fabricated tablets were carried out using USP eight-
stage dissolution testing apparatus-2 (paddle method) (Lab, India), at 50rpm in 500mL of
phosphate buffer solution, pH 6.8 at 37 0.5C. 5mL of aliquot was withdrawn at the
specified time intervals, filtered through Whatman filter paper and assayed
spectrophotometrically at 276nm and 230nm. An equal volume of fresh medium was
replaced into the dissolution medium after each sampling, to maintain the constant volume
throughout the test. Dissolution studies were performed in triplicate. Absorbance of these
solutions was measured at their respective max using a Double Beam UV Spectrophotometer.
42

6. RESULT AND DISCUSSIONS:

1. Observation Table:

S.no. + F1 F2 F3 F4 F5 F6 F7 F8 F9 F10

1 Average 2 248 248 250 249 250 248 248 249 2500.
weight(m 4 0.1 0.2 0.2 0.2 0.1 0.2 0.1 0.1 1
g) 8

0.
2

2 Drug 9 99.5 97.8 99.5 99.4 100. 98.2 99.5 98.3 98.2
content( 8. 6 3 1
%) 2

3 Disintegr 4 27 18 21 15 13 16 17 20 13
ation 9
time(sec)

4 Friability 0 0.51 0.43 0 0.41 0 0.43 0.51 0.42 0.45

(%)

5 Hardness 3 3 4.5 4 3.5 4 3.6 4 3.8 3.2

(kg/sqcm)

6 Wetting 3 32 12 27 27 10 13 17 27 27
time(sec) 6

7 Water 5 65 70 88 96 99 86 92 77 99
absorptio 2
n ratio
 43

vi. MICROMETRIC PROPERTIES FOR FORMULATION

Formulation Bulk Tapped Angle of repose()

density(gm/cm3) density(gm/cm3)

F1 0.428 0.501 29.88

F2 0.44 0.517 26.1
F3 0.46 0.54 27.54
F4 0.47 0.55 28.29
F5 0.458 0.524 26.34
F6 0.469 0.55 25.97
F7 0.43 0.57 23.21
F8 0.48 0.565 23.98
F9 0.427 0.598 27.87
F10 0.439 0.517 26.54

7. CONCLUSION:

Nature and concentration of the superdisintegrants showed influence on the rate of dissolution. The
rate of the drug release was found to be increased by increasing the concentration of the
superdiintegrants and found to be highest for tablets formulated with10 mg of superdisintegrants.

All the blend exbhited good flow properties and suited for direct compression. The compatibility
studies were conducted by FTIR. The results show the compatible nature between the drugs and
excipients. F6 offered relatively rapid release of Ibuprofen when compared with other formulations
increase in the concentrations of superdisintegrants may lead to increase in the drug release.
 44

REFERENCES

1. Int j curr pharm res, vol 9, issue 2, 8-18review article fast dissolving tablets: a review, ashish
masih, amar kumar, shivam singh*, ajay kumar tiwari School of Pharmaceutical
Science, Jaipur National University, Received: 25 Nov 2016, Revised and
Accepted: 23 Jan 2017

2. Prathiva T.K et al (2013) reported as A review of FDDS:A pioneer drug delivery system

3. Deepak Sharma et al (2014) reported as Formulation Development and Evaluation of Fast

Disintegrating Tablets of Salbutamol Sulphate, Cetirizine Hydrochloride in Combined
Pharmaceutical Dosage Form: A New Era in Novel Drug Delivery for Pediatrics and Geriatrics

4. Robertson sally et al (2014) reported as ibuprofen mechanism in news medical life science.

5. Pahwa R., Piplani M., Sharma P. C., Kaushik D., Nanda S. Orally disintegrating tabletsfriendly
to pediatrics and geriatrics. Archives of Applied Science Research. 2010;2(2):3548.

6. Divate S., Kavitha K., Sockan G. N. Fast disintegrating tabletsan emerging trend. International
Journal of Pharmaceutical Sciences Review and Research. 2011;6(2):1822.

7. Panigrahi R., Behera S. A. Review on fast dissolving tablets. Webmed Central Quality and
Patient. 2010;1(9):117.
 45

8. Newa Madhuri (2008) prepared and evaluated of fast dissolving Ibuprofen- polyethylene glycol
6000 solid dispersion.

9. Vaishali .Y. Londhe (2012) formulated and evaluated of fast dissolving film of Telmisartan.

10. Basu Biswajit (2011) formulated and evaluated of fast dissolving tablet of Cinnarizine using
super disintegrant blends and subliming material.

11. Sharma Deepak (2015) formulated and evaluated of fast disintegrating tablet of Salbutamol
sulphate, Cetrizine hydrochloride in combined pharmaceutical doses form: A new era in novel drug
delivery for Pediatrics and Geriatrics.

12. Gupta Sparsh (2015) Novel study in fast dissolving drug delivery system : A review.

13. Turnen Elina (2014) cyclodextrin in fast dissolving drug formulation for intraoral
administration.

14. Parmar Dipika (2012) reported as Orally fast dissolving films as dominant dosage form for
quick release.
46