International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 1, Issue 1, July-Sep.

2009
Research article

FORMULATION AND EVALUATION OF BUCCOADHESIVE BI-LAYER

TABLET OF PROPRANOLOL HYDROCHLORIDE
DEELIP DERLE*, OMKAR JOSHI, ASHISH PAWAR, JATIN PATEL, AMOL JAGADALE
*E-mail: dvderle@yahoo.com
Department of Pharmaceutics, N.D.M.V.P. Samajs, College of Pharmacy, Gangapur Road, Nashik-422002, Maharashtra, India.
Received- 29 March 09, Revised and Accepted- 13 April 09

ABSTRACT
The purpose of the study was to formulate and evaluate mucoadhesive bi-layer buccal
tablets of propranolol hydrochloride tablets using the bioadhesive polymers such as
sodium alginate and carbopol 971 P along with ethyl cellulose as an impermeable
backing layer. The tablets were evaluated for weight variation, thickness, hardness,
friability, surface pH, mucoadhesive strength, swelling index, in vitro drug release.
Tablets containing sodium alginate and carbopol 971 P in the ratio of 5:1 showed the
maximum percentage of in vitro drug release without disintegration in 12 hours. The
swelling index was proportional to sodium alginate content and inversely proportional to
carbopol 971 P content. The surface pH of all tablets was found to be satisfactory, close
to neutral pH; hence, no irritation would observe with these tablets. The mechanism of
drug release was found to be zero-order kinetics.
Keywords : Mucoadhesion bi-layer tablet, Buccal drug delivery, Propranolol hydrochloride.
required2.

INTRODUCTION

terminate

Buccal delivery of drug provides an

Attempts have been made to formulate

alternative to the oral route of drug

various buccal mucoadhesive dosage

administration. In recent years, delivery

forms,

of therapeutic agents through various

patches5, disks6 and gels7. A suitable

trans-mucosal routes gained significant

buccal drug delivery system should

attention owing to their pre-systemic

possess good bioadhesive properties, so

metabolism or instability in the acidic

that it can be retained in the oral cavity

environment

oral

for the desired duration and should

administration . Buccal delivery provides

release the drug in a unidirectional way

direct entry of drug into the systemic

toward the mucosa, in a controlled and

circulation, thus avoiding the hepatic

predictable manner, to elicit the required

first-pass

of

therapeutic response. This unidirectional

administration, and making it possible to

drug release can be achieved using bi-

associated

with

effect,

ensuring

ease

delivery

including

when

tablets3,

films4,

206

layer tablet dosage form6,8. Propranolol

mannitol) were purchased from local

hydrochloride,

vendor. All other reagents and chemicals

nonselective

beta-

adrenergic blocking agent, has been

used were of analytical grade.

widely

EXPERIMENTAL

used

in

the

treatment

of

hypertension, angina pectoris, and many

Preparation of buccal tablets

other

disorders.

Bi-layer buccal tablets were prepared by

Propranolol hydrochloride is subjected

a direct compression method using two

to an extensive and highly variable

steps. Various batches were prepared by

hepatic first pass metabolism following

varying the ratio of CP and Na-alginate

oral administration, with a reported

to

systemic bioavailability of between 15%

formulation. The mucoadhesive drug/

cardiovascular

9,

and 23%.

10

identify

the

most

effective

. The physicochemical

polymer mixture was prepared by

properties of propranolol hydrochloride,

homogeneously mixing the drug with

its half-life of 3 to 5 hours, and its low

CP, Na-alginate, PVP, Perlitol, and PEG

molecular weight of 295.81 make it a

6000 in a polybag for 15 minutes as

suitable candidate for administration by

shown in Table 1. The mixture 100 mg

11

the buccal route .

was then compressed using a 12 mm

MATERIALS AND METHODS

diameter

Propranolol hydrochloride, carbopol 971

multistation

P (CP), and ethyl cellulose (EC) were

Minipress I, Ahmedabad, India). The

obtained

from

upper punch was raised and the backing

Glenmark pharmaceuticals Ltd, Nashik,

layer of EC was placed on the above

Sodium-alginate (300-400 cps) (Na-

compact; the two layers were then

Alginate), polyethylene glycol 6000

compressed into a mucoadhesive bi-

(PEG 6000), polyvinyl pyrrolidone K-30

layer tablet. Each tablet weighed 150 mg

(PVP),

with a thickness of 1.5 to 1.6 mm.

as

and

gift

Perlitol

samples

(Spray

dried

die

in

tablet

single

machine

stroke
(Rimek

Table 1 : Formulation of buccoadhesive tablets.

Sr. no.
1
2
3
4
5
6
7

Ingredients (mg/tab)

F1

Adhesive layer
Propranolol hydrochloride
20
Sodium alginate
34.3
Carbopol 971P
5.7
PVP K30
30
Perlitol
8
PEG 6000
2
Backing layer
Ethyl cellulose
50
Total
150

F2

F3

F4

F5

20
33.4
6.6
30
8
2

20
32
8
30
8
2

20
30
10
30
8
2

20
26.7
13.3
30
8
2

50
150

50
150

50
150

50
150

207

Content uniformity

method USP type VI apparatus (Disso

Drug content uniformity was determined

Lab India, India) at 37 0.50 C at 100

by dissolving the tablets in ethyl alcohol

rpm using phosphate buffer pH 6.8.6, 12.

and filtering with whattman filter paper

The goat buccal mucosa was adhered to

(0.45 m). The filtrate was evaporated

the cylinder by using cynoacrylate glue.

and the drug residue dissolved in 100 ml

The disk was pressed on the mucosa

phosphate buffer pH 6.8. The 5 ml

gently with the finger for 1 minute. The

solution was then diluted with phosphate

time of disk adhered to mucosa was

buffer pH 6.8 up to 20 ml, filtered

measured and results are given in Table 2.

through whattman filter paper, and

Table 2: Ex-vivo mucoadhesion time

analyzed at 290 nm using a UV Double

of formulation

beam

spectrophotometer

(Shimadzu

Formulation

Adhesion time
Hours SD

F1

7 0..98

average values reported.

F2

9 0.76

In-vitro mucoadhesion time

F3

11 1.34

Adhesion time of formulations were

F4

10 1.98

determined by using rotating cylinder

F5

8 0.98

11

2501 PC, Japan.) . The experiments

were

performed

in

triplicate,

and

Table 3 : Evaluation of tablet parameter

Formulation

% weight
variation

F1

Thickness Hardness
(mm)

(kg/cm )

%
Friability

0.820.15

1.60.98

4.320.16

0.650.05

100.60.3

F2

0.720.21

1.50.34

4.230.34

0.650.09

98.450.5

F3

0.860.17

1.60.75

4.000.35

0.740.03

99.40.4

F4

0.630.12

1.70.56

4.230.46

0.750.06

97.560.5

F5

0.840.12

1.50.86

3.980.32

0.760.04

100.50.8

Swelling study

%Drug
content

from the petri dish and excess surface

weighed

water was removed carefully using filter

individually (W1) and placed separately

paper. The swollen tablet was then reweighed

in 2% agar gel plates with the core

(W2), and the swelling index (SI) or

facing the gel surface and incubated at

percent hydration was calculated using the

37 0.10 C. The tablet was removed

following formula6 and given in Fig. 2

Buccal

tablets

were

% of hydration = (W2-W1) X 100 / W2

208

Where,

speed of 50 rpm. The backing layer of

W1- initial weight of tablet

the buccal tablet was attached to the

W2- weight of disks at time t

glass slide with cyanoacrylate adhesive.

Surface pH study

The disk was placed at the bottom of the

The surface pH of the buccal tablets was

dissolution vessel. 5 ml samples were

determined.

withdrawn

In-vitro drug release

intervals

USP type II rotating paddle method was

medium. The samples were filtered

used to study the drug release from the

through 0.2- m Whatman filter paper

bi-layer tablet. The dissolution medium

and analyzed after appropriate dilution

consisted of 600 ml of phosphate buffer

by UV Double beam spectrophotometer

pH

at 290 nm11. The results are shown in Fig. 1.

6.8.

The

release

study

was

at
and

predetermined
replaced

with

time
fresh

Cumulative percent drugrelease

performed at 37 0.50 C, with a rotation

100

F1
F2
F3
F4
F5

80
60
40
20
0

10

12

Time in Hours

Fig. 1 : In-vitro drug release study

Swelling Index

60

F1
F2
F3
F4
F5

40

20

10

15

Time in Hours

Fig. 2: Swelling index study

209

RESULT AND DISCUSSION

property of Na-alginate compared with

CP and Na-alginate were selected as the

CP. The maximum swelling index was

bioadhesive polymers because of their

found in batch F1 (481.23), containing

6,16-18

a higher proportion of Na-alginate, and

EC has recently been reported to be an

the lowest in F5 (220.23). Tablets did

excellent backing material, given its low

not show any appreciable change in their

water permeability, hydrophobicity, and

shape and form during the 8 hours they

moderate flexibility19, so it was chosen

were kept on the 2% agar gel plate. This

as

backing layer.

finding is owing to the hydrophilic

Perlitol and PVP-K30 were used to

nature of Na-alginate; it is hydrated

improve the release of drug from

easily with less contact time and forms a

polymer matrices, and the concentration

strong gel that entangles tightly with the

was optimized during the preliminary

mucin molecules. Tablets containing

trial to find the best formulation of bi-

Na-alginate and CP in the ratio of 5:1

layer buccal tablets as shown in Table 1.

(F2) had the maximum percentage of in

Tablets were found to be satisfactory

vitro drug release without disintegration

when evaluated for weight variation

in 12 hours.

(0.78 0.15%), thickness (1.5 0.18 mm)

CONCLUSION

excellent bioadhesive properties.

an

impermeable

kg/cm2),

The mucoadhesive buccal tablets of

friability (0.72 0.04%),and drug

propranolol hydrochloride can help to

content (99.79 0.62%). The surface pH

bypass

of all the tablets was within a range of 5-

metabolism

6 as shown in the Table 3, close to

bioavailability.

neutral

tablets showed a mucoadhesion time of

hardness

(4.005

pH.

0.41

Appropriate

swelling

extensive
and
The

hepatic

first-pass

hence

improve

buccal

bi-layer

behavior of a buccal adhesive system is

more than 12 hours.

essential for uniform and prolonged

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