International Journal of Pharmaceutical Sciences

INT.J.PH.SCI.,MAY-AUG, 2010;2(2):488-495
ISSN 0975-4725
www.ijps.info

Original Research Manuscript

FORMULATION AND EVALUATION OF ORAL DISINTEGRATING TABLETS OF

LABETOLOL HYDROCHLORIDE

J.Ramesh*, Dr.V.Prabhakar Reddy, Dr.G.chandrasekhar Rao.

St.peter’s Institute of Pharmaceutical Sciences, Naimnagar, Hanamakonda-506001, Andrapradesh, India.
*Corresponding author E-mail address: ramesh_jadhav73@yahoo.com

ABSTRACT
Purpose of this research work was to mask the bitter taste of Labetolol HCL and to prepare oral disintegrating tablets. Taste is
masked by complexing the Labetolol HCL with amino alkyl methacrylate copolymer (Eudragit EPO) by solvent evaporation method.
Different ratio of drug complex was prepared. Then these drug complexes were evaluated for assay, dissolution study in simulated saliva
fluid. The complex which is prepared by using 1:4 ratios did not release drug in saliva so it is selected. The tablets were prepared by direct
compression method and different ratios of various super disintegrants were incorporated. Then these tablets were evaluated for hardness,
friability, weight variation, water absorption ratio, disintegrating time, dissolution. Taste evaluation was done by spectrophotometric
method and by panel testing. F8 batch shows good disintegration time (60 sec) than the other batches. In simulated saliva fluid (pH 6.8)
only less amount of drug is released from the tablets by it confirmed that complexation achieved and successfully taste is masked.
KEYWORDS Rapid disintegrating tablets, Eudragit EPO, Labetolol hydrochloride, Super disintegrants.

INTRODUCTION rapidly disintegrate in mouth with little amount of water or even

Oral disintegration tablets are the novel technology for
administration of the drug through the oral route. Many
pharmaceutical dosage forms are administered in the form of
pills, granules, powders and liquid, which results in high
1
incidence of non-compliance and ineffective therapy . Many
patients find it difficult to swallow like paediatric and geriatric2, 3
4-6
and those people who are travelling or little access to water and
some patients who are mentally ill like schizophrenia they are
also did not take medicine, oral disintegrating tablets solve these
problems. An Oral disintegration tablets is an solid dosage form
that disintegrates and dissolves in the mouth without water
7,
within 60 seconds or less .Rapid disintegrating tablet that is
with saliva8 drug dissolution and bioavailability significantly
increases than the conventional dosage form9-10. Oral
disintegrating tablets also applicable when local action is need in
the mouth such as local anesthetic for toothaches, oral ulcers,
cold sores or teething11 and also these oral disintegrating tablets
applicable to deliver sustained release multi particulate system to
those who have difficulty in swallowing tablets/capsules.
Labetolol hydrochloride is an anti hypertensive drug. Labetolol
hydrochloride when take by oral route it 90-100% of the drug
absorbed through GI tract, but the drug under goes first pass
metabolism in liver/GI mucosa. Oral disintegrating tablet avoid
first pass effect and increase its bioavailability. Labetolol

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J.Ramesh et al: FORMULATION AND EVALUATION OF ORAL DISINTEGRATING TABLETS OF LABETOLOL
HYDROCHLORIDE

hydrochloride very bitter in taste if it is incorporated directly in ñ b = bulk density

oral disintegrating tablets they are not accepted by patient due to If the hausner ratio is less than 1.25 indicates better flow
bitter taste. So in the present study drug taste is masking then property.
preparing oral disintegrating tablets with good mouth feel,
patient friendly dosage form. EVALUATION OF TABLETS
Weight variation 14
MATERIALS AND METHODS Twenty tables were selected randomly. Weigh individually to
Labetolol hydrochloride (Ref No: 978/31/SPIPS/Wgl/2007) was check for weight variation.
a gifted from Neuland laboratories limited (Hyderabad, India) Friability
Amino alkyl methacrylate co polymer (Eudragit EPO) was gifted It is determined by using roche friabalator. This device subjects
from orchid pharmaceuticals (Chennai, India). The the tablets to the abression and shock in a plastic chamber
superdisintegrants were cross povidone (Danmed pharma pvt revolving at 25 rpm and dropping the tablet at height of 6 inches
Ltd, Hyderabad), cross carmellose sodium (Amish Drugs & in each revolution. The tablets were pre weighed and place them
chemicals, Ahmadabad), and sodium starch glycolate (Amish in to the friabalator and subjected to 100 revoluation. After 100
Drugs & chemicals, Ahmadabad) revolutions the tablets were reweighed. Then calculate friability
by the given equation.
EVALUATION OF BLENDS F= (1-Wo/W) 100
12
Bulk density Wo = weight of the tablet before the test
It is measured by the pouring the powder in to a measuring W = weight of the tablet after the test
cylinder. Then initial volume was noted. This is called as bulk Hardness
volume (Vo). From this bulk density is calculated by the Hardness was measured by using Monsanto hardness tester.
following formulae. Thickness
ñ b = M/ V p Thickness of the tablets was measured by using digital varnier
Where ñ b = Bulk Density calipers.
M = Weight of sample in gm Disintegration time
3
V o = volume of blend in cm The in-vitro disintegration time was determined by using
Tapped density disintegrating apparatus. A tablet was placed in to each of the six
The measuring cylinder containing a known mass of blend was tubes of the apparatus and one disk was added to each tube. The
tapped for a fixed time. The volume was measured (Vt). The time was recorded after completion of the disintegration of the
tapped density was calculated by the following formulae. tablets.
ñ t = M/ V t Water absorption ratio15
Compressibility index A small culture Petri dish can be taken containing 6ml of water
It is calculated by the following formulae and a piece of tissue paper folded twice was placed. A tablet was
I = vo – v t / vo X 100 placed gently on it and the time for complete wetting was
Hauser ratio13 measured. The wetted tablet was reweighed.
It is used for flow property of the blend. It is calculated by the Water absorption ratio R was determined according the following
following formulae. equation:
H= ñ t / ñ b R = (Wa-Wb) / Wb * 100
ñ t = tapped density

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J.Ramesh et al: FORMULATION AND EVALUATION OF ORAL DISINTEGRATING TABLETS OF LABETOLOL
HYDROCHLORIDE
Where Wa is the weight of tablet after water absorption & Wb is
the weight of tablet before absorption.
Dissolution
The in-vitro dissolution study was carried out in USP dissolution
test apparatus Type 2(paddle) with a dissolution medium of 500
0
ml of 0.1N HCL at 50 rpm (37±0.5 C). 10 ml sample was
withdrawn at the 5 min time intervals and same amount of fresh
dissolution medium is replaced in dissolution apparatus after
withdrawn. The samples were analyzed by UV visible double
beam spectrophotometer. The dissolution of the drug was
expressed as percentage drug dissolved at the end of 5min
PREPARATION OF DRUG POLYMER COMPLEX
Labetolol Hcl and Eudragit EPO complex were prepared by
using the solvent evaporation method in various ratios 1:1, 1:2,
1:3, 1:4, 1:5. In this 1:4 ratio shows better masking property than
other. So 1:4 ratio of drug polymer complex is selected for tablet
preparation. Labetolol Hcl and Eudragit EPO were dissolved in
absolute ethanol. Then this mixture was maintained at 350c for 2
hrs on magnetic stirrer. The co-precipitated mixture was then
0
evaporated on a water bath at 45 c for 8h, and further dried under
vaccum at 450c for 24 hrs. Collect the dried complex and
pulverized stored in a tight closed container for further studies.
FORMULATION OF ORAL DISINTEGRATING
TABLETS
Tablets were prepared by direct compression method. Accurately
weighed amount of 500 mg of DPC was taken and add the other
ingredient as per table1. All the ingredients were passed through
the sieve no.60.Tablets were punched by using 12/32 flat
punches on sixteen-station rotary tablet compression machine.
RESULT AND DISCUSSION
Characterization of DPC
Taste evaluation was done by taste panel method by using 6
healthy male human volunteers (Table 4), and
spectrophotometer method. The tablet conducted for dissolution
H
using P 6.2 buffer. Only 2mg of the drug released after 5 min
(figure 3).
490
FTIR was conducted for DPC for complexation. As shown in the
in figure 4, a broad band of bonded –OH of Labetolol Hcl was
observed from 3354.81 to 3188.73 cm-1. DPC showed shifting of
this peak from 3400 to 3189.86 cm-1. Shifting of DPC peaks
indicates the formation of new N-H stretching, which was
previously absent in the drug.
Physical Properties of the Tablet Blend
The blend of all the batches showed good flow property (angle of
repose < 300). Hausner ratio is an indirect index of ease of
powder flow (Table 2). All the formulations show less than 0.88
indicates that better flow property (Acceptable range is less than
1.25)
Evaluation of Tablets
Hardness of all formulations was measured in Kg/cm2 using
Monsanto tester (table 3). Hardness of the all formulation was
between 3-4 Kg/cm2 during compression. The friability of all
formulations has below the 0.84%, indicating that the tablets
were mechanically stable and could handle the rigors of
transportation and handling. Weight variation test was
performed. The weights of all tablets were found between 599-
603 mg. as the weight of tablets was 600mg, the acceptable
weight range is  10%. Hence all tablets passed the weight
variation test. Percentage drug content of all formulations was
found to be between 95% - 102%, which was within the
acceptable limits. From the results of dissolution of all
formulations (figure 1), tablets F8 batch show complete drug
release With in 10 min. and show disintegration time less when
compared with other formulations.
CONCLUSION
Drug Eudragit complex is prepared by solvent evaporation
method. Eudragit satisfactorily mask the bitter taste of Labetolol.
The dissolution experiment showed that the less amount of drug
is released in pH 6.8 media, therefore the drug is not expected to
release in saliva after oral administration. The good
by disintegrating property is depending on the water absorption ratio
of the excipient. From the study it is concluded that cross
povidone shows good disintegrating property than cross
carmellose, sodium starch glycolate.
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HYDROCHLORIDE
Table 1: General Composition of all Formulations

Ingredient (mg) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12

DPC 500 500 500 500 500 500 500 500 500 500 500 500
CP - - - - 15 30 45 60 - - - -
SSG 15 30 45 60 - - - - - - - -
CCS - - - - - - - - 15 30 45 60
SS 14 14 14 14 14 14 14 14 14 14 14 14
Talc 06 06 06 06 06 06 06 06 06 06 06 06
MS 06 06 06 06 06 06 06 06 06 06 06 06
Mannitol 59 44 29 14 59 44 29 14 59 44 29 14

DPC-Drug polymer complex, CP- Cross povidone, SSG- Sodium Starch Glycolate, SS-Sodium Saccharin, MS- Magnesium Stearate

Table 2: Evaluation of Mixed blend of Drug and excipients

Angle of repose Bulk density Tapped density Compressibility index

Formulation Hausner ratio
() (gm/ml) (gm/ml) (%)
F1 26.5 2.4 2 16.6 0.66
F2 16.6 2.4 2.1 12.5 0.87
F3 24.2 2.5 2.15 14 0.86
F4 23.71 2.6 2.3 11.5 0.88
F5 30.5 2.4 1.8 25 0.75
F6 29.68 2.5 2.1 16 0.84
F7 28.81 2.4 1.9 20.83 0.79
F8 27.02 2.5 2 20 0.8
F9 26.5 2.5 2 20 0.8
F10 27.47 2.4 2 16.66 0.83
F11 27.02 2.6 2.1 19.23 0.80
F12 25.17 2.5 1.9 24 0.76

Table 3: Evaluation of taste by human volunteers

V1 V2 V3 V4 V5 V6
High bitter taste --- --- --- --- --- ---

Less bitter taste --- --- --- ---

Acceptable --- ---

sweet --- --- --- --- --- ---

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HYDROCHLORIDE

Table 4: Evaluation of tablets

Formulation Assay
Weight variation Hardness Friability In-vitro dis integration time Thickness
Water absorption ratio (%)
(mg) (% w/w) (sec) (mm)
F1 601.4±1.67 3-4 0.5 100 5.90 66 102.12
F2 602±1 3-4 0.52 110 6 62 98.21
F3 601.4±1.67 3-4 0.46 115 6.02 60 105.14
F4 602±0.7 3-4 0.50 120 6.01 58 101.01
F5 601.2±0.83 3-4 0.65 80 5.95 80 99.21
F6 601.8±0.86 3-4 0.75 74 5.98 86 101.21
F7 603±1.58 3-4 0.45 70 6.00 88 101.23
F8 599.8±0.83 3-4 0.65 60 6.02 90 102.21
F9 600±2.34 3-4 0.24 84 5.98 78 101.32
F10 601.2±2.38 3-4 0.48 80 6.00 80 99.25
F11 599.6±1.51 3-4 0.84 78 6.02 82 101.32
F12 600.4±1.67 3-4 0.76 76 5.98 84 101.21

Figure 1: Drug Release profile of all Formulations

Figure 2: Water absorption ratio

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J.Ramesh et al: FORMULATION AND EVALUATION OF ORAL DISINTEGRATING TABLETS OF LABETOLOL
HYDROCHLORIDE
Figure 3: Release profile of Batch 8 in PH 1.2 and in PH 6.2 Buffer

Figure 4: Water absorption ratio

Before Wetting After Wetting-F1 After Wetting-F2

After Wetting-F3 After Wetting-F4 After Wetting-F5

After Wetting-F6 After Wetting-F7 After Wetting-F8

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HYDROCHLORIDE

After Wetting-F9 After Wetting-F10 After Wetting-F11

After Wetting-F12

Figure 5: FTIR Spectras of Labetolol, Eudragit EPO and Labetolol Eudragit EPO complex

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