IJRPC 2011, 1(3) Borgaonkar et al.

ISSN: 22312781

INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY

Available online at [Link] Research Article

FORMULATION AND IN VITRO EVALUATION OF BUCCAL TABLETS OF

LORATADINE FOR EFFECTIVE TREATMENT OF ALLERGY
Borgaonkar PA*, Virsen TG, Hariprasanna RC and Najmuddin M
Department of Pharmaceutics, RMES’S College of Pharmacy, Gulbarga, Karnataka, India.

*Corresponding Author: prashant7522@[Link]

ABSTRACT
Mucoadhesive buccal tablets of Loratadine were prepared with an objective of enhancing
the bioavailability by minimizing first pass metabolism. The buccal tablet were prepared
by using HPMC K4M as primary polymer alone and in combination with secondary
polymers like Chitosan, Sodium alginate in varying concentration by direct compression
method. Estimation of Loratadine was carried out spectrophotometrically at 248 nm. The
tablets were evaluated for hardness, thickness, weight variation, friability, drug content,
surface pH, swelling index, in vitro drug release, mucoadhesive strength and also the effect
of secondary polymer concentration on these parameters was studied. Short-term stability
studies (40±2o C/75±5% RH for 3 months) indicated that the buccal tablets are stable with
respect to drug content and dissolution. FTIR spectroscopic studies indicated that there are
no drug-excipient interactions. All the tablets showed good mucoadhesive strength of 4.00
to 7.00 gm and force of adhesion increased with increase in polymer concentration and
drug release reduced consequently. The surface pH of the tablet was in the range of 6.7 to
6.9 which does not irritate mucosa. The formulations HP1 (containing 30% HPMC K4M)
was found to be promising, which showed t50%, t70% and t90% values of 3.20 h, 5.48h, 7.16 h
and drug released 99.00% within 8 h respectively. These formulations have displayed good
bioadhesion strength (4.0 gm).

Keywords: Loratadine, HPMC K4M, Sodium alginate, Chitosan.

INTRODUCTION
The interest in novel routes of drug in cases of toxicity by removing the dosage
administration is to increase the therapeutic form from the buccal cavity. It is an alternative
efficacy of the drug. Drug delivery via the route to administer drugs to patients who are
buccal route using bioadhesive dosage forms unable to be dosed orally. Therefore, adhesive
offers such a novel route of drug mucosal dosage forms are suggested for
administration. This route has been used buccal delivery, including adhesive tablets,
successfully for the systemic delivery of adhesive gels, and adhesive patches 1.
number of drug candidates. Problems such as Transmucosal routes of drug delivery (i.e., the
high first-pass metabolism and drug mucosal linings of the nasal, rectal, vaginal,
degradation in the harsh gastrointestinal ocular, and oral cavity) offer distinct
environment can be circumvented by advantages over peroral administration for
administering the drug via the buccal route. systemic drug delivery. These advantages
Moreover, buccal drug delivery offers a safe include possible bypass of first pass effect,
and easy method of drug utilization, because avoidance of presystemic elimination within
drug absorption can be promptly terminated the GI tract and depending on the particular

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drug, a better enzymatic flora for drug 2) Thickness 5, 7

absorption 2.
The thickness of three randomly selected
The strategy for designing buccoadhesives is
tablets from each formulation was determined
based principally on the utilization of
in mm using a Screw gauge.
polymers with suitable physicochemical
properties, such as polyacrylic acid (carbomer 3) Friability test 5, 8
[CB]) and cellulose derivatives
(hydroxypropylmethylcellulose [HPMC]) 3. The friability of tablet was determined by
Loratadine is tri-cyclic antihistamine, which using Roche Friabilator. It is expressed in
selectively antagonizes peripheral histamine percentage (%). Twenty tablets were initially
H1 receptor. Loratadine undergoes extensive weighed (Winitial) and transferred into
first-pass hepatic metabolism and has 40% friabilator. The friabilator was operated at 25
bioavailability, its half life is 8 hours 4. rpm for 4 minutes or run up to 100 revolutions
Therefore, a buccal tablet of Loratadine will be in which tablet droped from 6 inch distance.
formulated to prevent first-pass metabolism The tablets were dusted weighed again
and to improve therapeutic efficacy. (Wfinal). The percentage friability was then
calculated by,
MATERIALS AND METHODS
W initial – W final
Loratadine was gift sample from Cadila Pvt.
F= × 100
Ltd. Ahemadabad. All other reagents and
W
chemicals used were of analytical grade.
% Friability of tablets less than 1% is
considered acceptable.
Preparation of buccal tablets of Loratadine
by direct compression method 4) Uniformity of weight 5, 8
Direct compression method was employed to The weight variation test was performed as
prepare buccal tablets of Loratadine using per procedure of IP. The weight (mg) of each
HPMC K4M, Chitosan, Sodium alginate as of 20 individual tablets, selected randomly
polymers. All the ingredients including drug, from each formulation was determined by
polymer and excipients were weighed dusting each tablet off and placing it in an
accurately according to the batch formula and electronic balance. The individual weight was
were passed through #40 to get uniform compared with average weight for
particle size. The drug and all the ingredients determination of percent deviation.
except lubricants were taken on a butter paper
with the help of a stainless steel spatula and 5) Uniformity of drug content 9
the ingredients were mixed in the order of Five tablets were powdered in a glass mortar
ascending weights and blended for 10 min in and the powder equivalent to 10 mg of drug
an inflated polyethylene pouch. After uniform was placed in a stoppered 10 ml conical flask.
mixing of ingredients, lubricant was added The drug was extracted with 60% methanol
and again mixed for 2 min. The prepared with vigorous shaking and filtered into 10 ml
blend of each formulation was compressed by volumetric flask. Further appropriate dilution
using 7mm punch on a single stroke tablet were made by using phosphate buffer pH 6.8
punching machine (Rimek, minipress rotary to make 10 mcg/ml concentration and
machine, Karnavathi engineering ltd, Gujarat.) absorbance was measured at 248 nm against
blank (phosphate buffer pH 6.8).
Evaluation of mucoadhesive buccal tablets of
6) Surface pH study 10
Loratadine
A combined glass electrode is used for this
1) Hardness test 5, 6
purpose. The tablet is allowed to swell by
The hardness of the tablets was determined
keeping it in contact with 1 ml of phosphate
using Monsanto Hardness tester. It is
buffer pH 6.8 for 2 h at room temperature.
expressed in Kg/cm2. Three tablets were
The pH is identified by bringing the electrode
randomly picked from each formulation and
into contact with the tablet surface and
the mean and standard deviation values were
allowing to equilibrate for 1 min.
calculated.

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7) Swelling Index 10 mean value of three trials was taken for each
The swelling index of the buccal tablet was set of formulations. After each measurement,
evaluated in phosphate buffer pH 6.8 The the tissue was gently and thoroughly washed
initial weight of the tablet was determined and with phosphate buffer and left for 5 minutes
then tablet was placed in 15 ml phosphate before placing a new tablet to get appropriate
buffer pH 6.8 in a petridish and then was results for the formulation.
incubated at 37  1o C. The tablet was removed
at different time intervals (0.5, 1.0, 2.0, 3.0, 4.0,
5.0, 6.0, 7.0 and 8.0 h) blotted with filter paper
and reweighed (W2). The swelling index is
calculated by the formula:

Swelling index = 100 (W2-W1) / W1.

Where, W1 = Initial weight of the tablet.

W2 = Final weight of tablet.

8) Mucoadhesion strength 11
Prior to the study approval was obtained from
Institutional Animal Ethics Committee (Reg.
No.-341/CPCSEA). Mucoadhesion strength of
the tablet was measured on a modified
Figure 1: Bioadhesion testing apparatus
physical balance (Figure 1.) employing the
method as described by Gupta et al using
sheep buccal mucosa as model mucosal 9) In vitro drug release study 8
membrane. Fresh sheep buccal mucosa was The study was carried out in USP XXIII tablet
obtained from a local slaughter house and was dissolution test apparatus-II (Campbell
used within 2 h of slaughtering. The mucosal electronics, DR-6 Dissolution Appratus),
membrane was washed with distilled water employing paddle stirrer at 50 rpm and 900 ml
and then with phosphate buffer pH 6.8. A of phosphate buffer pH 6.8 with 0.5% Tween
double beam physical balance was taken and 80 as dissolution medium maintained at
to the left arm of balance a thick thread of 370.5 0C. At different time interval 5 ml of
suitable length was hanged and to the bottom sample was withdrawn and replaced with
side of thread a glass stopper with uniform fresh medium. The samples were filtered
surface was tied. The buccal mucosa was tied through 0.25 μm membrane filter paper and
tightly with mucosal side upward using analyzed for Loratadine after appropriate
thread over the base of inverted 50 ml glass dilution at 248 nm using PG instrument T80
beaker which was placed in a 500 ml beaker model UV-Visible spectrophotometer.
filled with phosphate buffer pH 6.8 kept at 37o The results of in vitro release profiles obtained
C such that the buffer reaches the surface of for the formulations were fitted into four
mucosal membrane and keeps it moist. The models of data treatment as follows :
buccal tablet was then stuck to glass stopper 1. Cumulative percent drug released
from one side membrane using an adhesive versus time (zero order kinetic model).
(Feviquick). 2. Log cumulative percent drug
The two sides of the balance were made equal remaining versus time (first- order
before the study, by keeping a weight on the kinetic model).
right hand pan. A weight of 5 g was removed 3. Cumulative percent drug released
from the right hand pan, which lowered the versus square root of time ( higuchi’s
glass stopper along with the tablet over the model).
mucosal membrane with a weight of 5 g. The 4. Log cumulative percent drug released
balance was kept in this position for 3 min. versus log time (korsmeyer - Peppas
Then, the weights were increased on the right equation).
pan until tablet just separated from mucosal
membrane. The excess weight on the right pan 10) Short Term Stability studies 12
i.e. total weight minus 5 g was taken as a Short- term stability study was performed at a
measure of the mucoadhesive strength. The temperature of 40 ±2o C over a period of three

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months (90 days) on the promising buccal month interval for evaluation of drug content
tablets of Loratadine. Sufficient numbers of and in vitro drug release study.
tablets (10) were individually wrapped using
aluminium foil and packed in amber colour 11) Polymer drug interaction study 12
screw cap bottle and kept in stability chamber The drug-polymer and polymer-polymer
for 3 months. Samples were taken at each interaction was studied by FTIR spectrometer
using Shimadzu 8400-S, Japan.

RESULT
Table 1: Composition of Buccal Tablet of Loratadine.
Ingredients Formulation code
mg/tablet HP1 HP2 HP3 HC1 HC2 HC3 HS1 HS2 HS3
Loratadine 10 10 10 10 10 10 10 10 10
HPMC K4M 30 40 50 50 50 50 50 50 50
Chitosan -- -- -- 5 10 15 -- -- --
Sodium
-- -- -- -- -- -- 5 10 15
Alginate
Mannitol 38.8 28.8 18.8 13.8 8.8 3.8 13.8 8.8 3.8
MCC 20 20 20 20 20 20 20 20 20
Mg. Stearate 1 1 1 1 1 1 1 1 1
Sodium
0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
saccharine
Total 100 100 100 100 100 100 100 100 100

Table 2: Physicochemical Properties of Buccal Tablets

Weight
Formulation Hardness Thickness Friability Variation Drug
code Kg/cm 2 * (mm)* (%)* of Tablet Content (%)*
(mg) *
HP1 5.4±0.06 3.20±0.06 0.55±0.00 98±0.99 97.41±0.34
HP2 5.5±0.03 3.25±0.06 0.51±0.01 100±0.38 98.23±0.38
HP3 5.6±0.02 3.29±0.00 0.87±0.03 101±0.99 100±0.88
HC1 5±0.05 3.23±0.06 0.50±0.00 98±0.99 100±0.56
HC2 4.5±0.02 3.26±0.06 0.32±0.02 98±0.38 98.70±0.33
HC3 4±0.07 3.33±0.00 0.75±0.01 99±0.99 96.98±0.84
HS1 6±0.04 3.21±0.06 0.20±0.02 101±0.17 97.84±0.41
HS2 5±0.08 3.25±0.01 0.66±0.01 99±0.40 97.41±0.54
HS3 4.5±0.03 3.31±0.00 0.41±0.01 99±0.20 98.70±0.58
*Average of three determinations.

Table 3: Result of Surface pH, Swelling Index

and Mucoadhesive Strength of all Formulations
Swelling
Formulation Mucoadhesive
Surface pH* Index
code Strength
After 8 hr
HP1 6.9±0.17 22.06 4.000
HP2 6.8±0.12 27.73 4.900
HP3 6.7±0.11 31.80 6.350
HC1 6.9±0.17 16.01 6.500
HC2 6.9±0.23 20.86 6.550
HC3 6.8±0.32 25.61 6.700
HS1 6.8±0.07 18.21 6.400
HS2 6.7±0.02 21.76 6.900
HS3 6.6±0.06 27.20 7.000
*Average of three determinations,

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Table 4: In Vitro Drug Release Parameters

Cumulative %
Formulation t70% t90%
t50% (h) drug release
code (h) (h)
in 8 hrs
HP1 3.20 5.48 7.16 99.00
HP2 4.18 6.03 7.53 91.23
HP3 5.00 6.26 >8.00 85.45
HC1 4.13 6.05 >8.00 83.80
HC2 5.00 6.24 >8.00 82.15
HC3 5.30 7.05 >8.00 77.61
HS1 4.46 6.26 >8.00 82.56
HS2 5.33 7.18 >8.00 75.96
HS3 5.54 7.58 >8.00 70.18

Table 5: Kinetic Data of Formulations of Mucoadhesive Tablets

Formulation Zero Higuchi Peppas
r First Order
Code Order equation equation
HP1 r 0.9876 -0.1945 0.9707 0.7556
HP2 r 0.9896 -0.1628 0.9652 0.7609
HP3 r 0.9919 -0.0736 0.9645 0.7781
HC1 r 0.9955 -0.1236 0.9635 0.8570
HC2 r 0.9963 -0.0721 0.8991 0.8662
HC3 r 0.9954 0.0183 0.9497 0.8858
HS1 r 0.9983 -0.0676 0.9625 0.8758
HS2 r 0.9951 0.0294 0.9433 0.8802
HS3 r 0.9932 0.0645 0.9360 0.9111

14
12
10
Time (hrs)

8
6 T50 %
4 t70%
2
0 t90%
HP1
HP2
HP3
HC1
HC2
HC3
HS1
HS2
HS3

Formulation

Figure 2: Comparison of dissolution parameters

( t50%, t70% and t90%) of buccal tablets of Loratadine.

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120

Cumulative percent drug release

100 HP1
HP2
80
HP3
60 HC1

40 HC2
HC3
20
HS1
0 HS2
0 5 10 HS3
Time (hrs)

Figure 3:Cumulative percent drug release vs time

2.5
HP1
Log cumulative percent drug

2 HP2
HP3
remaining

1.5
HC1
1 HC2
HC3
0.5
HS1
0 HS2
0 2 4 6 8 10HS3
Time (hrs)

Figure 4.: Log cumulative percent drug

remaining vs time plots (first order)

120
Cumulative percent drug release

HP1
100
HP2
80
HP3
60 HC1
40 HC2
20 HC3
0 HS1

-20 0 1 2 3 HS2
Square root of time HS3

Figure 5: Cumulative percent drug released vs square

root of time plots (Higuchi plots)

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2.5
HP1

LOg cumulative percent drug

2 HP2
1.5 HP3

release
1 HC1
0.5 HC2
0 HC3
0 0.5 1 HS1
Log time (hrs) HS2

Figure 6: Log cumulative percent drug released vs log

Time plots (Peppas plots)

130

100
%T

50

0
-10
4000 3000 2000 1000 400
Wavenumber[cm-1]
Figure 7: IR spectrum of Loratadine

110
100

80
%T

60

40

20
10
4000 3000 2000 1000 400
Wavenumber[cm-1]
Figure 8: IR spectrum of HP1

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DISCUSSION CONCLUSION
It could be observed that all the prepared It can be concluded that the buccal tablets of
tablets fulfil the the requirements of buccal Loratadine can be prepared by using natural
tablets. The hardness of prepared buccal polymers to control the drug release and also
tablets was found to be in the range of 4.00 to to avoid the first pass metabolism. The
6.00 kg/cm2 and shown in Table-2. The formulations HP1 was found to be promising,
thickness and weight variation were found to which shows an in vitro drug release of 99% in
be uniform as indicated by the low values of 8 h along with satisfactory mucoadhesion
standard deviation. The thickness and weight strength i.e 4.00 gm and t50%, t70%, and t90% was
of the prepared buccal tablet were found to be 3.20, 5.48, 7.16 respectively.
in the range of 3.20 to 3.33 mm and 98 to 101
mg respectively. Friability values of all tablets
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