1122 International Journal of Pharmaceutical Sciences and Nanotechnology

Volume 3 Issue 3 October-December 2010

International Journal of Pharmaceutical Sciences and Nanotechnology

Volume 3 Issue 3 October - December 2010

Research Paper

Development and Evaluation of Guaifenesin Bilayer Tablet

B. Vijaya Kumar *, G. Prasad, B. Ganesh, C. Swathi, A. Rashmi, G. Amarender Reddy
Janagoan institute of pharmaceutical sciences, Jangoan, India

ABSTRACT:

The objective of the present research was to develop a Bilayer tablet of guaifenesin (GBT) using
superdisintegrant MCC and sodium starch glycolate for the fast release layer and metalose 90 SH and carbopol 934 for the
sustaining layer. The guaifenesin SR granules of different formulation were evaluated for bulk density, tapped density, angle
of repose, Carrs index and Hausners ratio and results were found to be 0.460 0.12 to 0.515 0.03 gm/cm3 , 0.550 0.03
to 0.590 0.04 gm/cm3 , 19 0.01 to 26 0.23, 13.72 0.03 to 19.56 0.04 & 1.137 to 1.196, respectively. The prepared
bilayer tablets were evaluated for weight variation, hardness, friability, drug content and in vitro drug release. In vitro
dissolution studies were carried out in a USP 24 apparatus I. The formulations gave an initial burst effect to provide the
loading dose of the drug followed by sustained release for 12 h from the sustaining layer of matrix embedded tablets. In
vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial
burst release. Stability studies conducted for optimized formulation did not show any change in physical appearance, drug
content, matrix integrity and in vitro drug release. The results of the present study clearly indicated that GBT was a stable
dosage form and a promising potential of the guaifenesin bilayer system as an alternative to the conventional dosage forms.

KEYWORDS: GBT, Guaifenesin, Bilayer, immediate release, control release

Introduction
In the last few years controlled release dosage forms have
made significant progress in terms of clinical efficacy and
patient compliance. The objective of designing a controlled
release system is to deliver drug at a rate necessary to
achieve and maintain a constant drug blood level (Makhija
et al., 2002; Acevez et al., 2000). The multilayered tablet
concept has been long utilized to develop sustained release
formulations. Such a tablet has a fast releasing layer and
may contain bi- or triple layers to sustain the drug release.
The pharmacokinetic advantage relies on the fact that drug
release from fast releasing granules leads to a sudden rise
in the blood concentration. However, the blood level is
maintained at steady state as the drug is released from the
sustaining granules (Abraham et al., 1997; Makhija et al.,
2002; Rahman et al., 2006; Uzdemir et al 2000).
Guaifenesin is an expectorant, a drug which increases
respiratory tract fluid secretions and helps to loosen
phlegm and bronchial secretions. Guaifenesin is readily
absorbed from the intestinal tract and is rapidly
metabolized and excreted in urine but has a short plasma
* For correspondence: B. Vijaya Kumar,
Tel: +91-9849084556, +91-9951098762
E-mail: vijaypharmacy2000@yahoo.com

1122

half-life of one hour. Because of the rapid metabolization

and excretion of guaifenesin, typical immediate release
dosage tablets of guaifenesin provide only short window of
therapeutic effectiveness for patients and require multiple
dosing for maintaining therapeutic effect throughout day;
hence there is a potential need for sustained dosage form.
In comparison with the single sustain layer tablet, a double
layer containing one immediate release compartment and
one sustain release layer offers advantages (Thummel et al
2006; Check et al 1982; Bennett et al 2004).
The objective of present study was to develop
guaifenesin Bilayer tablet by wet granulation technique
and also evaluated their precompression and post
compression properties

Materials and Methods

Materials
All the materials used were of pharmaceutical grade of
purity. Guaifenesin was obtained as a gift sample from
Ajantha Pharma. Ltd., Bombay. Microcrystalline cellulose
pH 102, Metalose 90 SH and Carbopol 934 was procured
as a gift sample from Dr. Reddys Laboratories,
Hyderabad, polyvinayl pyrrolidine K30 (PVP K30),
starch, sodium starch glycolate, magnesium stearate, talc,

B. Vijaya Kumar, et.al. : Development and Evaluation of Guaifenesin Bilayer Tablet

aerosol was purchased from M/s S.D. fine chemicals

Mumbai. All other solvents and reagents were of analytical
grade.

Methods
Preparation Bilayer tablets
The Bilayer tablets of guaifenesin were prepared by wet
granulation technique composition of each table is shown
in Table 1, it consists of three step process.
Step 1 formulation of immediate release granules:
Guaifenesin was passed through # 40 and all the other
components (as per the formulae given in table 1) were
passed through no. 60 sieve, then thoroughly mix and then
granulated with 10% w/w starch paste. The wet mass was
passed through #10 and the granules were dried at 45oC for
a period of 2 hr in hot air oven. The dried granules were
passed through # 20 and lubricated with magnesium
stearate by further blending for 3mins and finally talc was
added to the blend.
Table 1 Formulae of Guaifenesin immediate release
layer.
Composition

granules were passed through # 20 and lubricated with

magnesium stearate by further blending for 3 mins and
finally talc was added to the blend.
Step 3 compression of Bilayer tablet: Accurately
weighted quantity of immediately release and sustain
release granules were compressed on 10 station Rimek
tablet compression machine (M/s Karnawati Engg. Ltd.
Ahemadabad) using 12 mm punches (Abraham et al.,
1997; Makhija et al., 2002).
Evaluation of SR granules
Prior to the compression into tablets SR granules were
evaluated for properties like Bulk density, tapped density,
powder flow properties i.e., angle of repose, carrs index
and hausner ratio. Bulk density and tapped density were
measured by using bulk density apparatus.
Flow properties of powders was measured by (Staniforth J
2002; Rawlins EA 1996; Martin et al 2002; Ansel et al
2002; Guyot et al 1998)
(i) Angle of repose: It was measured by using funnel
method and calculated by using formula
= tan-1 (h/r)

Weight Per Tablet (mg)

Guaifenesin
MCC pH 102

= angle of repose
h = height in cm of pile
r = radius

Where

100
60

Sodium starch
glycolate
Starch
Purified water

10

(ii) Carrs index was calculated by using formulae

5
QS

D t Db
100
Dt

I=

* Magnesium stearate, Talc and Aerosil were used as

glidents and lubricants at 1%

Dt = Tapped density

Where

Step 2 formulation of sustain release granules:

Guaifenesin was passed through # 40 and all the other
components (as per the formulae given in table 2) were
passed through no. 60 sieve, then thoroughly mix and then
granulated with 20% w/w PVP K 30 paste. The wet mass
was passed through #10 and the granules were dried at
45oC for a period of 1 hr in hot air oven. The dried

Db = Bulk density
(iii) Hausner ratio was calculated by
H=

Dt
Db

Table 2 Formulae of Guaifenesin sustain release layer.

Ingredients (mg/tablet)

Formulations
F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

500

500

500

500

500

500

500

500

500

500

Metalose 90SH

10

10

12

14

16

18

20

Carbopol 934

10

10

10

10

10

10

10

Guaifenesin

MCC pH 102

PVP K 30

20

20

20

20

20

20

20

20

20

20

Magnesium stearate

Talc
Purified water

1123

QS

QS

QS

QS

QS

QS

QS

QS

QS

QS

1124 International Journal of Pharmaceutical Sciences and Nanotechnology

Evaluation of Bilayer Tablets

Post compression parameters

Volume 3 Issue 3 October-December 2010

describe the drug release behavior from polymeric systems

(Korsmeyer et al 1983; Peppas NA 1985; Harland et al
1988)

The prepared tablets were evaluated for weight variation,

hardness, thickness, friability and drug content uniformity
In weight variation, 20 tablets were randomly selected
from each batch and weighed individually; thereafter
average weight and standard deviation of 20 tablets were
calculated. Hardness was measured by using Pfizer
hardness tester. Thickness of tablets was measured by
using digital vernier caliper. Friability was measured by
taking randomly 20 tablets which was weighed and placed
in the friabilator and rotated at 25 rpm for a period of 4
min. After revolution the tablets were dusted and weighed.
Finally drug content uniformity was calculated.
Guaifenesin Absorbency was measured at 256nm, using
double beam UV visible spectrophotometer (elico) (Ansel
et al 2002; Merchant et al 2006; Bourne DW 2002).
In vitro Drug Releases Studies
In vitro dissolution studies were performed by using USP
XXIV dissolution apparatus type II at 100 rpm. Dissolution
test was carried out using 900ml of 0.1N HCl, at 37
0.5oC. A 5ml sample of solution was withdrawn from the
dissolution apparatus hourly and the samples were replaced
by fresh dissolution medium then the samples were filtered
and absorbancy were measured at 274nm using UV/Visible
spectrophotometer (Costa et al 2001; Wagner 1969; Cobby
et al 1974; Pather et al 1998; Merchant et al 2006; Guyot et
al 1998).
Kinetic analysis of dissolution data
The rate and mechanism of release of guaifenesin from the
prepared bilayer tablets were analyzed by fitting the
dissolution data into the zero-order equation
Q = k0t
Where Q is the amount of drug released at time t, and
k0 is the release rate constant, fitted to the first order
equation
ln (100 Q) = ln 100 k1t
Where k1 is the release rate constant. The dissolution
data was fitted to the Higuchis equation (Higuchi et al
1988; Higuchi T 1963, Higuchi T 1961)
Q = k2 t1/2
Where k2 is the diffusion rate constant.
The dissolution data was also fitted to the well known
equation (Korsmeyer equation), which is often used to

log (Mt/M) = log k + n log t

Where Mt is the amount of drug released at time t, M
is the amount of drug release after infinite time, k is a
release rate constant incorporating structural and geometric
characteristics of the tablet and n is the diffusional
exponent indicative of the mechanism of drug release
(Thummel et al 2006; Merchant et al 2006; Bourne DW
2002; Guyot et al 1998; Brabander et al 2002).
Stability studies
Stability studies were performed according to ICH and
WHO guidelines. Optimized GBT formulations were strip
packed in laboratory in aluminum foil with polyethylene
lamination and various replicates were kept in the humidity
chamber maintained at 45oC and 75% RH and 37oC for 3
months. At the end of studies, samples were analyzed for
the drug content, in vitro dissolution, floating behavior and
dimensional stability (Mathews BR 1999; Sharma et al
2005; Brabander et al 2002).

Results and Discussions

The guaifenesin SR granules of different formulation from
F 1 to F 10 were evaluavted for bulk density, tapped
density, angle of repose, carrs index and hausners ratio
(as shown in Table 3). The results of bulk density and
tapped density ranges from 0.460 0.12 to 0.515 0.03
gm/cm3 & 0.550 0.03 to 0.590 0.04 gm/cm3 and angle of
repose, carrs index and hausners ratio were found to be 19
0.01 to 26 0.23, 13.72 0.03 to 19.56 0.04 & 1.137 to
1.196 respectively.
The prepared bilayer tablets were evaluated for various
physical properties. All the batches were produced under
similar conditions to avoid processing variables. These
were evaluated for physical parameters such as weight
variation, hardness, friability and drug content as shown in
Table 4. Hardness of tablets were ranged from 6.5 0.50
to 8.0 0.5 kg/cm2, thickness of the tablets ranged from
5.8 0.21mm to 6.2 0.65mm. The percentage friability
of all formulation was between 0.132 0.02 to 0.672
0.04%. The drug content uniformity was within the range
from 95.4 0.12% to 99.4 0.67%. All the different
formulations of prepared tablets of good quality with
regard to hardness, thickness, friability and drug content.
All the tablets complied with pharmacopeial specification
for weight variation and friability.

B. Vijaya Kumar, et.al. : Development and Evaluation of Guaifenesin Bilayer Tablet

1125

Table 3 Precompression properties of guaifenesin SR granules.

Formulation
Code

Bulk density
(gm/cm3)

Tapped density
(gm/cm3)

F1

0.460 0.12

0.550 0.03

22 0.02

19.56 0.04

1.196

F2

0.505 0.05

0.575 0.02

19 0.01

13.86 0.08

1.139

F3

0.480 0.15

0.560 0.12

22 0.03

16.66 0.10

1.167

F4

0.490 0.04

0.565 0.06

23 0.02

15.30 0.02

1.153

F5

0.500 0.07

0.570 0.07

21 0.09

14.00 0.05

1.140

F6

0.515 0.03

0.590 0.04

20 0.08

14.56 0.12

1.146

F7

0.495 0.11

0.572 0.10

23 1.11

15.55 0.07

1.156

F8

0.510 0.01

0.580 0.02

21 0.09

13.72 0.03

1.137

Angle of repose
()

Carrs index
(%)

Hausner ratio
(%)

F9

0.480 0.09

0.560 0.14

23 1.15

16.66 0.05

1.167

F 10

0.460 0.12

0.544 0.05

26 0.23

18.26 0.02

1.183

Mean SD n=6

Table 4 Post compression properties of GBT.

Formulation

Weight variation

Hardness

Thickness

Friability

Drug content

Code

(mg)

(kg/cm )

(mm)

(%)

(%)

F1

710 0.16

6.5 0.50

6.2 0.31

0.236 0.02

96.4 0.32

F2

720 0.75

7.5 0.23

5.8 0.21

0.436 0.03

95.4 0.12

F3

725 1.02

7.0 0.76

6.2 0.01

0.376 0.05

96.3 0.08

F4

725 0.98

7.5 0.56

6.0 0.43

0.672 0.04

98.4 0.23

F5

730 0.78

7.5 0.43

5.9 0.34

0.132 0.02

99.4 0.32

F6

730 0.58

6.5 0.67

6.2 0.23

0.543 0.03

98.6 0.45

F7

732 0.73

6.0 0.5

5.9 0.16

0.265 0.02

96.4 0.65

F8

735 0.25

8.0 0.5

6.0 0.20

0.191 0.01

99.4 0.67

F9

738 0.43

7.5 0.54

6.1 0.18

0.334 0.04

99.4 0.45

F 10

740 0.62

8.0 0.19

6.2 0.65

0.543 0.02

98.4 0.25

Mean SD n=6

Dissolution studies
In vitro dissolution studies are valuable tools to judge
stability and quality of sustain release dosage forms and
often used to predict the in vivo performance.
The release of guaifenesin from prepared formulations
was analyzed by plotting the cumulative percent drug
release vs. time as shown in fig. 1. From the graph its
shows an initial burst release i.e., over 20% of guaifenesin
was released within first half an hour of dissolution study.
This initial high amount of guaifenesin release can be
attributed to release of drug from the immediate release
layer of the formulation. The initial release of guaifenesin
was due to MCC and SSG. The initial release of GBT with
low concentration of metalose 90SH in F 1 to F 3 was very
high compared to other formulation. This high percent
release can be ascribed to release of drug from the

immediate release layer and also release of drug from the

surface of sustained release layer of the tablet.
The release rate was found to be decreasing as the
concentration of metalose 90SH increase in F 4 to F 8.
This is due to swelling is less because of higher
concentrations of polymer. In F 8 cumulative percent drug
release was about 99% in 12hr; further release rate was
found to be very less as increase in the concentration of
metalose 90SH from F 9 to F10. Drug release kinetic from
the F 8 exhibit best correlation by Higuchi equation
proving that the release is by diffusion mechanism as
shown in Table 5, Koresmeyer and Peppas equation
revealed that F 8 formulation have n value 0.493 indicates
that they follow Non-fickian diffusion.
Stability studies were carried out at 45 C and 75% RH
for three months (climatic zone IV condition for
accelerated testing) to assess their long-term (2 years)

1126 International Journal of Pharmaceutical Sciences and Nanotechnology

stability of CBT formulation. The protocols of stability

studies were in compliance with the guidelines in the
WHO document for stability testing of products intended
for the global market. After storage, the formulation was
subjected to a drug assay, floating behavior and in vitro

Volume 3 Issue 3 October-December 2010

dissolution studies. The statistical analysis of the parameter

of dissolution data (F 2 = 80.23), floating behavior and
drug content after storage at 45 C and 75% RH for three
months in the Table 6 showed no significant change.

110
100
90

cu m u lative % D ru g release

80
70
60
50
40
30
20
10
0
0

10

11

12

Time in hours
F1

F2

F3

F4

F5

F6

F7

F8

F9

F 10

Fig. 1 Dissolution profile of different formulations of GBT.

Table 5 Diffusion Kinetics and Model Fitting Data of GBT.
Drug rlease kinetics, correlation coefficient r
Formulation

Release exponentional in
Korsmeyer & Peppas (n)

Zero order

First order

Higuchi

F1
F2

0.8318
0.8289

0.9474
0.9560

0.9276
0.9362

Korsmeyer
and peppas
0.8283
0.8326

F3

0.8448

0.9676

0.9431

0.8456

0.723

F4
F5
F6
F7

0.7871
0.8873
0.8337
0.8366

0.9149
0.9431
0.8706
0.8211

0.9317
0.9862
0.9785
0.9782

0.8214
0.9519
0.9655
0.9721

0.546
0.554
0.488
0.496

F8

0.8662

0.9285

0.9893

0.9899

0.498

F9
F 10

0.8717
8276

0.7903
0.8052

0.9888
0.9736

0.9721
0.9732

0.486
0.474

0.718
0.699

B. Vijaya Kumar, et.al. : Development and Evaluation of Guaifenesin Bilayer Tablet

1127

Table 6 Comparison characteristics of GBT before and after storage.

Before storage a,b

After storage a,b

99.4 0.67

98.28 2.36

Hardness ( kg/cm )

8.0 0.523

8.0 0.527

Matrix integrity

Very good

Very good

Parameters
Drug content (%)
2

Similarity factor(F 2)

80.23

Storage at 45C/75% RH for three months.

Mean SD, n = 6

Conclusion
In this study the GBT was prepared by using fast releasing
components for immediate release, Metalose 90SH and
Carbopol polymers were used for sustain release. GBT
showed biphasic release in the first phase, the first fraction
of the dose (immediate dose) was released as a burst effect
in less than 60 minutes, because of fast releasing
components of loading layer then second phase was
released from matrix layer as a controlled non fickian
diffusion release fashion. Thus, results of the current study
clearly indicate, GBT was a stable dosage form and a
promising potential of the bilayer system as an alternative
to the conventional dosage form. However, further clinical
studies are needed to assess the utility of GBT.

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