IAJPS 2015, Volume2 (5), 886-893

K. Ramesh Reddy et al

ISSN 2349-7750

ISSN 2349-7750
INDO AMERICAN JOURNAL OF

PHARMACEUTICAL SCIENCES

Available online at: http://www.iajps.com

Research Article

DESIGN, DEVELOPMENT AND IN-VITRO EVALUATION OF

METOPROLOL TARTRATE FAST DISSOLVING TABLETS
K. Ramesh Reddy*1, V. Jayasankar Reddy1 G. Saisri Harsha1, K. Anil2
1. Krishnateja Pharmacy College, Tirupati-517506, A.P,India
2. OTRI-JNTUA ,Anantapuram, A.P ,India
Abstract:
The main objective of the study is to formulate and evaluate oro-dispersible tablets of Metoprolol tartrate with
suitable superdisintegrantsMetoprolol Tartrate is effective -blocker used in the second line treatment for angina
and for myocardial infarction. Adult dose as conventional preparations is 25-100 mg daily in single or divided
doses, as extended release 100-200 mg once daily. The bioavailability of the drug when formulated as conventional
tablets is 40 % due to hepatic metabolism. The present investigation was undertaken with a view to develop a fast
dissolving tablet of Metoprolol tartrate which offers a new range of product having desired characteristics and
intended benefits prepared by direct compression method using different concentrations of superdisintegrant. Effect
of superdisintegrant on wetting time, drug content, in-vitro drug release, disintegration time has been studied.
Disintegration time increased with increase in the level of Croscarmellose while it decreased for Sodium starch
glycolate, the release was dependent on the aggregate size in the dissolution medium. It is concluded that
Metoprolol Tartrate fast dissolving tablets could be prepared using superdisintegrant with improved bioavailability
and rapid onset of action.
Keywords: Fast dissolving tablets, Metoprolol Tartrate, Croscarmellose sodium, Sodium starch glycolate,
disintegration time, in-vitro drug release.

Corresponding author:
K. Ramesh Reddy,

QR code

Krishnateja Pharmacy College,

Tirupati-517506, A.P,I ndia

Please cite this article in press as K. Ramesh Reddy et al, Design, Development and In-Vitro Evaluation of
Metoprolol Tartrate Fast Dissolving Tablets, Indo American J of Pharm Sci, 2015;2(5):886-893.

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IAJPS 2015, Volume2 (5), 886-893

INTRODUCTION:
A Solid dosage form containing medicinal
substances, which disintegrates rapidly usually within
a matter of seconds, when placed upon the tongue.
According to European pharmacopoeia, A tablet that
is to be placed in the mouth where it disperses rapidly
before swallowing [1].
Rapid Dissolving tablets are also known as Melt in
Mouth tablets Mouth dissolving tablets (MDT) Fast
disintegrating tablets (FDT) Orally disintegrating
tablets Rapid disintegrating tablets (RDT) Oro
dispersible tablets (ODT) Quick dissolving tablets.
Fast Dissolving Tablets (FDT) disintegrates and/or
dissolves rapidly in the mouth without the need for
water. Some tablets are designed to dissolve in saliva
remarkably fast within a few seconds. Others contain
agents to enhance the rate of tablet disintegration in
the oral cavity and are more appropriately termed
Fast Dissolving Tablets (FDT) as they may take up to
a minute to complete disintegration of these
formulations is convenience. A major claim of the
some Fast Dissolving Tablets (FDT) increased
bioavailability compared to traditional tablets.
Because of dispersion in saliva while still in the oral
cavity, there can be pre-gastric absorption from some
formulation in those cases where the drug dissolves
quickly. Buccal, pharyngeal and gastric regions are
all areas of absorption of the many formulations.
However, other formulations show nearly identical
plasma concentration profiles. Any pre-gastric
absorption avoids first pass metabolism and can be a
great advantage in drugs that undergo a great deal of
hepatic metabolism.
Criteria for Fast Dissolving Drug Delivery System
[16]:
The tablets should
Not require water to swallow, but it should dissolve
or disintegrate in the mouth in matter of seconds.
Be compatible with taste masking.
Be portable without fragility concern.
Have a pleasant mouth feel.
Leave minimum or no residue in the mouth after oral
administration.
Exhibit low sensitive to environmental condition as
temperature and humidity.
Allow the manufacture of the tablet using
conventional processing and packaging equipments at
low cost.
Salient Feature Of Fast Dissolving Drug Delivery
System [3,4]
Ease of Administration to the patient who cannot
swallow, such as the elderly, stroke victims,
bedridden patients, patient affected by renal failure
and patient who refuse to swallow such as pediatric,

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K. Ramesh Reddy et al

ISSN 2349-7750

geriatric & psychiatric patients.

No need of water to swallow the dosage form, which
is highly convenient feature for patients who are
traveling and do not have immediate access to water.
Rapid dissolution and absorption of the drug, which
will produce quick onset of action.
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
increased.
Pregastric absorption can result in improved
bioavailability and as a result of reduced dosage;
improve clinical performance through a reduction of
unwanted effects.
Good mouth feel property helps to change the
perception of medication as bitter pill particularly in
pediatric patient.
The risk of chocking or suffocation during oral
administration of conventional formulation due to
physical obstruction is avoided, thus providing
improved safety.
New
business
opportunity
like
product
differentiation, product promotion, patent extensions
and life cycle management.
Beneficial in cases such as motion sickness, sudden
episodes of allergic attack or coughing, where an
ultra rapid onset of action required.
An increased bioavailability, particularly in cases of
insoluble and hydrophobic drugs, due to rapid
disintegration and dissolution of these tablets.
Stability for longer duration of time, since the drug
remains in solid dosage form till it is consumed. So,
it combines advantage of solid dosage form in terms
of stability and liquid dosage form in terms of
bioavailability.
Techniques for Preparing Fast Dissolving Tablets:
[5]
Many techniques have been reported for the
formulation of Fast dissolving tablets or
Orodispersible tablets.
1. Freeze drying / lyophilization
2. Tablet Moulding
3. Spray drying
4. Sublimation
5. Direct compression
6. Mass extrusion

MATERIALS AND METHODS:

Table 1 shows the chemical/reagent and drugs and
their source. And table 2 shows the source of
instruments used for this study.

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K. Ramesh Reddy et al

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Table 1: Source of Chemicals and Ingredients

S. No.

Ingredients/chemicals/solvents

Manufacturer /supplier

Mannitol, Crosscarmellose

SD fine chemicals, Boisar

Sodium starch glycolate

SD fine chemicals, Boisar

Methanol

SD fine chemicals, Boisar

Lactose

. SD fine chemicals, Boisar

Magnesium stearate

SD fine chemicals, Boisar

Starch

SD fine chemicals, Boisar

Talc

SD fine chemicals, Boisar

All the chemical were of AR grade

Table 2: Manufacturers of Instruments/Apparatus

S. No.

Instrument/Apparatus

Manufacturer/ Supplier

Tablet Press (9 Station, Single Rotary)

ChamundaPharma, Ahmadabad.

Friabilator

Singhala Scientific, Ambala.

Dissolution Apparatus (USP Type II)

Electrolab, Mumbai.

Monsanto Hardness Tester

Singhala Scientific, Ambala.

U.V.Visible Spectrophotometer

Shimadju, Mumbai.

Digital VernierCaliperse

Digimate, Hyd.

pH meter

Systronic, Hyd.

Stability study chamber

Electrolab, Mumbai.

Formulation of Tablets:
Fast dissolving tablets of Metoprolol tartrate were
prepared by direct compression. The term direct
compression is defined as the process by which
tablets are compressed directly from powder mixture
of API with suitable excipients. No pretreatment of
the powder blend by wet or dry granulation
procedure is required it done by simple mixing of

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API with suitable additive and compress to tablets.

All the ingredients (except granular directly
compressible excipients) were passed through 60mesh separately. Then the ingredients were weighed
and mixed in geometrical order and compressed into
tablets of 450 mg using 9 mm round flat punches on
9 - station rotary tablet machine.

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IAJPS 2015, Volume2 (5), 886-893

K. Ramesh Reddy et al

ISSN 2349-7750

Table 3: Formulation of Fabricated Oro Disintegration Tablets

Ingredients(mg)
Drug
Mannitol
MCC
Crosscarmellose
Sodium
Sodium Starch
glycolate
Magnesium
Stearate
Flavouring ang
Sweeting agent

FM-I
50
150
94
13

FM-II
50
150
92
14

FM-III
50
150
90
22

FM-IV
50
150
94
-

FM-V
50
150
92
-

FM-VI
50
150
90
-

13

14

22

12

10

12

10

31

32

33

31

32

33

Pre formulation studies

Bulk density:
Bulk Density is defined as weight per unit volume.
Bulk density (pb) is defined as the mass of the
powder divided by the bulk volume and is expressed
as gm/ cm3. A sample of about 50 cm3(blend) is
carefully introduced in a 100ml graduated cylinder.
The cylinder is dropped onto a hard wood surface
three times from a height of 1 inch at two second
interval. The bulk density is then obtained by
dividing the weight of sample in gm by final volume
in cm3.
Pb = M/ Vp
Pb = Bulk Density
M = Weight of sample in gm
Vp = Initial volume of blend in
cm3
Bulk density is very important in designing the size
of containers needed for handling, shipping, and
storage of raw material and blend.
Tapped density:
It is the ratio of total mass of the product to the
tapped volume of powder the volume was measured
by tapping the powder for fifty times.
Dt = M/Vt
Where, M is the mass of the powder
Vt is the tapped volume of the powder
Compressibility index:
Is an important measure that can be obtained from the
bulk and tapped densities.
CI = Tapped Density Bulk Density
/Tapped density*100
Angle of repose:
It is defined as the maximum angle possible between
the surface of a pile of powder and the horizontal
plane. Fix the funnel at a distance of 6cm and pass
the granules to fixed funnel and note down the height
and radius of the pile.
= tan-1 (h/r)

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Where, is the angle of repose

h is the height in cms and r is the radius in cms
Porosity:
The porosity of powder is defined as the ratio of
void volume to the bulk volume of the packaging.
The porosity of the powder is given = Vb - Vp/ Vp
= 1- Vp/Vb
Porosity is frequently expressed in percentage and is
given as
% = (1 - Vp/ Vb) X 100
The porosity of powder indicates the types of
packaging a powder undergoes when subject to
vibrations, when stored, or in tablet machine when
passed through hopper or feed frame.
Evaluation of Tablets
Hardness Test:
The crushing strength of the tablets was measured
using a Monsanto hardness tester. Three tablets from
each formulation batch were tested randomly and the
average reading noted.
Friability Test:
The friability test of a sample of 20 tablets was
measured using a Roche Friabilator. Twenty pre
weighed tablets were rotated at 25 rpm for 4 minutes.
The tablets were then reweighed after removal of
fines (using no. 60 mesh screen), and the percentage
of weight loss was calculated.
Weight Variation:
Randomly, twenty tablets were selected after
compression and the mean weight was determined.
None of the tablets deviated from the average weight
by more than 10% (USPXX).
Drug Content
Twenty tablets were weighed and powdered. An
amount of the powder equivalent to 100 mg of
Metoprolol tartrate was dissolved in 100 ml of pH
6.8phosphate buffer, filtered, diluted suitably and
analyzed for drug content at 243 nm using UV-

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K. Ramesh Reddy et al

Visible spectrophotometer.
Wetting Time:
A piece of tissue paper folded twice was placed in a
small petridish (ID=6.5 cm) containing 6 ml of
simulated saliva pH 6.8, a tablet was put on the
paper, and the time for complete wetting was
measured.
Thickness:
Ten tablets from each formulation were taken
randomly and their thickness was measured with a
micrometer screw gauge.
Disintegration Time:
Disintegration time for MDTs was determined using
USP disintegration apparatus with SSF (pH 6.2, 900

ISSN 2349-7750

ml at 37C) as the disintegrating medium. To comply

the test all tablets should disintegrate within 3
minutes.
In-vitro Drug Release Studies:
The in vitro dissolution study was carried out in USP
dissolution test apparatus Type 2 (Electro lab,India)
.The dissolution medium consisted of phosphate
buffer (pH 6.8). An amount of 900 ml of the
dissolution fluid was used at 370.50C with stirring
speed of 50 RPM Samples were withdrawn at 2, 4, 8,
10,and16 minutes time intervals by replacing with
same dissolution medium and samples were analyzed
by measuring the absorbance at 254 nm by UV
spectrophotometer.

RESULTS AND DISCUSSION:

Table: 4 Evaluation of granules:
Formulation Code

Bulk Density
gm/cm3

Tapped Density
gm/cm3

Compressibility Index (%)

Angle of Repose

F-I

0.45 0.04

0.57 0.01

10.00 0.04

32032 1.03

84.3 0.88

F-II

0.52 0.05

0.62 0.02

13.33 0.04

280 86 1.03

83.8 0.98

F-III

0.45 0.07

0.62 0.01

25.21 0.04

27042 1.25

92.6 0.68

F-IV

0.42 0.04

0.59 0.01

19.20 0.04

27034 1.15

91.3 0.76

F-V

0.39 0.03

0.45 0.03

13.30 0.04

29065 1.21

93.50 0.91

F-VI

0.47 0.04

0.61 0.04

21.66 0.04

28023 1.16

92.80 0.55

% porosity

Table: 5 Evaluations of Tablets

Formulation

Hardness
Kg/cm2

Friability
%SD

Weight
Variation
mgSD

Drug
Content
(%)

Wetting
time

Disintegration
time
(Sec SD)

Thickness
(mm SD)

(sec SD
FM I

3.5 0.02

0.66 0.16

449 0.41

98.51

21 0.22

68 0.12

4.19 0.01

FM II

3.5 0.09

0.54 0.16

451 0.25

98.78

19 0.12

72 0.09

4.55 0.01

FM III

2.7 0.10

0.56 0.16

450 0.39

99.81

38 0.14

69 0.11

4.65 0.01

FM IV

2.5 0.05

0.52 0.16

448 0.35

99.21

56 0.18

92 0.12

4.32 0.02

FM V

3.0 0.07

0.68 0.16

450 0.21

99.54

48 0.18

83 0.17

4.21 0.01

FM VI

3.7 0.03

0.51 0.16

451 0.22

98.99

69 0.19

91 0.21

4.69 0.02

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IAJPS 2015, Volume2 (5), 886-893

The present investigation was undertaken to

formulate and evaluate fast dissolving tablets of
Metoprolol tartarate by direct compression method
using Croscarmellose sodium and Sodium Starch
Glycolate as a superdisintegrants. Superdisintegrant
are generally used by formulation scientists for
developing FDTs or for improvement of solubility for
drugs. The primary requirement for both dosage
forms is quicker disintegration. The amount of Super
disintegrants was optimized in the formulation of
FDTs. The total 6 formulation (FM-IFM-VI) were
prepared
using
different
concentration
of
Croscarmellose sodium and Sodium Starch Glycolate
to study its effect on disintegration time.
Mannitol because of its negative heat of solution
gives cooling sensation and mask after bitter taste of
aspartame. Microcrystalline cellulose has also been
used as a diluent which helps in enhancing the
disintegration of the tablet. Magnesium stearate is
used as lubricant. The sweetener combination
aspartame and mannitol gives long lasting sweet taste
to the formulation. Vanillin acts as a flavouring
agent.
The present investigation was planned to formulate
and evaluate Metoprolol tartrate fast dissolving
tablets (FDT), using different excipients and super
disintegrates in various proportions prepared by
direct compression technique. The preparation
process in direct compression tablets includes cogrinding of all the excipients before compression
resulting, the increase in the solubility due to the
reduction in the effective particle size of the drug
following increase in the wetting of drug particle by
the excipients and improved dissolution of drugs. The
precompression and postcompression evaluations
were taken over for the prepared granules and tablets
respectively. The in-vitro drug release studies have
been carried out pH 6.8. The values of precompression parameters evaluated were within
prescribed limits and indicated good free flowing
property is given in Table 5.
Bulk density was found to be between 0.39 0.03
and 0.52 0.05 and tapped density between 0.45
0.03 and 0.62 0.02 for all the formulations. The
percentage compressibility was calculated and was

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K. Ramesh Reddy et al

ISSN 2349-7750

found to be in the range of 10.00 0.04 and 25.21

0.04 which indicates a fairly good flowbility of the
powder blend. The good flowability of the powder
blend was also evidenced with angle of repose (range
of 270 34 1.15 to 320 32 1.03) which is below
40o indicating good flowability. The percentage
porosity was found to be in the range of 83.8 0.98
to 93.50 0.91. All the formulation shows the good
blend properties for direct compression and hence
tablets were prepared by direct compression
technology.
The values of post compression parameters evaluated
were given in Table 6&7. Percent weight variation
was observed between 448 0.35 and 451 0.25
which were well within the acceptable limit for
uncoated tablets as per United States Pharmacopoeia.
It is well known to formulation scientists that the
tablets with more hardness show longer
disintegration time. Since mechanical integrity is of
paramount importance in successful formulation of
FDTs, hence the hardness of tablets was determined
and was found to be in the range of 2.5 0.05 to 3.7
0.03Kg/cm2. Friability was observed between 0.51
0.16 and 0.68 0.16, which were below 1%
indicating sufficient mechanical integrity and
strength of prepared tablets. The disintegration time
for all formulations was found to be 68 0.12 92
0.12 seconds and wetting time was 19 0.12 to 69
0.19 seconds. The thickness of the tablet ranges from
4.19 0.01 to 4.69 0.02.
The drug release studies were performed on the
prepared formulations (FM I-FM VI) using
phosphate buffer pH 6.8 for 20min. Table No. 6
enlists the comparatives In vitro drug release data for
formulations FM I to FM VI. The percentage
release of Metaprolol tartarate at 20 min for
formulations FM- I to FM- VI showing 79.03%,
83.06%, 93.06%, 78.89%, 81.15%, and 83.44%
respectively. From the above results, the formulation
FM - III showed faster and maximum drug release
than the other formulations.

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Fig 1: Comparison of In vitro Drug Release of Formulation-1,2 and 3

Fig 2: Comparison of In Vitro Drug Release of Formulation-4, 5 and 6

CONCLUSION:
Fast oro-dispersible tablet is a promising approach
with a view of obtaining faster action of the drug and
would be advantageous in comparison to currently
available conventional forms. Fast dissolving tablets
of Metoprolol tartrate were prepared by direct
compression method using Croscarmellose sodium
and Sodium Starch Glycolate as a superdisintegrant.
The dosage form had a good balance over
disintegration time and mechanical strength.
In vitro drug release from the tablets shows
significantly improved drug dissolution. It
was concluded that in direct compression method,

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Crosscarmellose sodium (5 %w/w) act as a best and

suitable superdisintegrant. Fast dissolving tablets of
Metaprolol tartarate is successfully prepared by using
direct compression method, will surely enhance the
patient compliance, low dosing, rapid onset of action,
increased bioavailability, low side effect, good
stability and its popularity in the near future. Further
investigations are needed to confirm the in vivo
efficiency.

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REFERENCES:
1. Mahesh P. Ratnaparkhi, Mohanta G.P,
Lokesh Upadhyay. Review On: Fast
Dissolving Tablet. Journal of Pharmacy
Research. 2009; 2(1):5 12.
2. Kaushik D, Dureja H, Saini T. R. Mouth
Dissolving Tablets: A review. Indian Drugs.
2004, 41(4):187-193.
3. Debjit
Bhowmik,
Chiranjib.B,
Krishnakanth, Pankaj, R.Margret Chandira.
Fast Dissolving Tablet: An Overview.
Journal of Chemical and Pharmaceutical
Research. 2009; 1(1):163-177.
4. Biradar S. S, Bhagavati S. T, Kuppasad I. J.
Fast Dissolving Drug Delivery Systems: A
Brief Overview. Internet J. Pharmacology.
2006; 4(2):52-56.
5. Reddy Bijay Ghosh L.H, Rajneesh. Oral
disintegrating tablets of carvedilol. Indian
Journal
of
Pharmaceutical
Science.
2002:331-336.
6. Chang R.K, Guo X, Burnside B.A, Couch
R.A. Fast dissolving tablets. Pharm Tech,
2000; 24:52-58.
7. Reddy LH, Ghosh BR. Fast dissolving drug
delivery systems: A review of the literature.
Ind J Pharm Sci. 2002; 64(4):331-336.
8. Aurora J, Pathak V. Oral disintegrating
technologies: Oral disintegrating dosage
forms: An overview. Drug Deliv Technol.
2005; 5(3):50-54.

www.iajps.com

K. Ramesh Reddy et al
9.

10.

11.

12.

13.

14.

15.

16.

ISSN 2349-7750

Hamilton EL, Luts EM. Advanced Orally

disintegrating tablets bring significant
benefits to patients and product life cycle.
Drug Deliv Technol. 2005; 5(1): 34-37.
Habib W, Khankari R, Honts J. Fast
dissolving drug delivery systems. Crt Rev
Ther Drug Carrier Syst. 2000; 17(1): 61-72.
Lies M.C, Atherton A.D, Copping N.M.
Freeze-dried dosage forms and methods for
preparing same. 1993; US Patent 5:188,825.
Seager H. Drug-deliver products and the
zydis fast-dissolving dosage form. J. Pharm.
Pharmacol. 1998; 50:375-382.
Cirri M, Valleri M, Mura P, Maestrelli F,
Ballerini R. Development of fast- dissolving
tablets of flurbiprofen - cyclodextrin
complexes, Drug Dev. Ind. Pharm. 2005;
31(7):697-707.
Corveleyn S, Remon J. P. Formulation and
Production of rapidly disintegrating tablets
by Lyophilization Technique. Int. J. Pharm.
1997; 152:215 225.
Furtado S, Deveswaran R, Bharath S,
Basavaraj BV, Abraham S, Madhavan V.
Development and characterization of
orodispersible tablets of Famotidine
containing a subliming agent. Tropical
Journal of Pharmaceutical Research. 2008;7
(4):1185-1189.
Makino T, Yamada M, Kikuta J. Fast
dissolving tablet and its production,1993,
European Patent, 0553777 A2.

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