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Indo American Journal of Pharmaceutical Research, 2014

ISSN NO: 2231-6876

FORMULATION AND EVALUTION OF FLOATING DRUG DELIVERY SYSTEM OF


GUAIFENESIN TABLET
*

S.G.Waghmare1, Dr.D.M.Sakarkar2

Hi-Tech College of Pharmacy,Chandrapur.


Sudhakarrao Naik Institute of Pharmacy,Pusad.

ARTICLE INFO
Article history
Received 06/12/2014
Available online
19/12/2014

Keywords
Gastric Retention,
Floating Tablet,
Extended Release/
Sustained Release,
Guaifenesin.

ABSTRACT
Oral controlled release drug delivery have recently been of increasing interest in
pharmaceutical field to achieve improved therapeutic advantages, such as ease of dosing
administration, patient compliance and flexibility in formulation. Drugs that are easily
absorbed from gastrointestinal tract (GIT) and have short half-lives are eliminated quickly
from the systemic circulation. To avoid this limitation, the development of oral sustainedcontrolled release formulations is an attempt to release the drug slowly into the
gastrointestinal tract (GIT) and maintain an effective drug concentration in the systemic
circulation for a long time. The present study involves preparation of floating tablet of
Guaifenesin with HPMC K100 M and HPMC K15M floating tablet were designed to achieve
the extended release or retentions in GIT which may result enhance in absorption n leads to
increment in bioavaiblity. Enhanced floatability of tablet and its retentions period in GIT
directly enhanced bioavaiblity of drug and decreases the frequency of administration of drug.
Comparing the HPMC polymer grades K100 and K15 it concludes that the K100M shows
good result in a F4 batch.

Copy right 2014 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical
Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Please cite this article in press as Suchita Gulabrao Waghmare et al. Formulation and Evalution of Floating Drug Delivery
System of Guaifenesin Tablet. Indo American Journal of Pharm Research.2014:4(12).

5750

Corresponding author
Suchita Gulabrao Waghmare
Assistant Professor ,Hi-Tech College of Pharmacy,
Padoli phata,Nagpur-Chandrapur High-way,
At Morwa, Chandrapur.44.
Suchitawaghmare26@gmail.com

Vol 4, Issue 12, 2014.

Suchita Gulabrao Waghmare et al.

ISSN NO: 2231-6876

INTRODUCTION
One of the essential factors is the residence time of the drug at the absorption site. Over the last two decades,
numerous Gastroretensive dosage forms have been designed to prolong gastric residence time. They may be broadly classified
into: high-density (sinking) systems, low-density (floating) systems, expandable systems super porous hydrogel systems,
mucoadhesive systems and magnetic systems. They enable oral therapy by drugs with a narrow absorption window in the upper
part of the gastrointestinal tract or drugs with a poor stability in the colon. Furthermore, the drug can act locally within the
stomach and prolonged intimate contact with the absorbing membrane increases efficacy. [1]
One of the novel approaches in the area of oral sustained release drug delivery is gastro retentive drug delivery system
(GRDDS). Drugs those are having a narrow absorption window and having more solubility in gastric region are suitable candidates for
GRDDS[ 2].
Gastroretensive systems can remain in the gastric region for several hours and hence significantly prolong the gastric
residence time of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste and improves solubility for drugs
that are less soluble in a high pH environment. It has applications also for local drug delivery to the stomach and proximal small
intestines. Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial
benefits for patients [3]. This application is especially effective in delivery of sparingly soluble and insoluble drugs
Guaifenesin may be commonly used as an expectorant in both productive and non-productive coughs; it is especially useful
in the treatment of dry, Non-productive coughs which tend to injure the respiratory mucous membranes. Guaiphenesin helps loosen
phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus, drain bronchial tubes, and make
coughs more productive. Helps loosen phlegm and thin bronchial secretions in patients with stable chronic bronchitis. : Plasma half
life is approximately 1 hour. , makes it a useful candidate for controlled release dosage form and stability in the acidic environment is
useful for gastro-retentive drug delivery system.
The objective of this study include (1) developing floating drug delivery system containing drug and polymers (2) study on
the effect of polymers concentrations and processing parameter on floating and drug release behavior of the system and (3) selection
of the best formulation based on optimization techniques using evaluation parameters like floating lag time, total floating time and
release profile.
The objective of choosing the Guaifenesin was its short half life and to reduce dosing frequency in case cough.
MATERIAL AND METHOD
The following materials that were Pharma grade or the best possible Laboratory Reagent were used as supplied by the
manufacturer without further purification or investigation. Guaifenesin IP, HPMC K15M IP, HPMC K100M IP, Sodium Bicarbonate
LR, Citric Acid LR, Talc LR, Aerosil LR, Magnesium Stearate LR provided by blessing pharmaceutical India , Nagpur.
Preparation of Floating Tablets
Floating tablets of Guaifenesin were prepared by direct compression technique using different grades of polymer with varying
concentration. As shown in table. All the ingredients except magnesium Stearate were blended in mortor uniformly. After the
sufficient mixing of drug as well as other components, magnesium Stearate was added and again mixed for additional 2-3 min. The
well mixed mixture equivalents to 740 mg were compressed using 12mm flat faced punch on clit compression machine.
Table 1:The tablet formulation used in current studies shown in following.
Ingredients

F1

F2

F3

F4

F5

F6

F7

F8

F9

Guaifenesin

300

300

300

300

300

300

300

300

300

HPMC K-100M

240

260

280

300

--

--

HPMC K-15M

--

--

--

--

240

260

280

300

150

Sodium Bicarbonate

70

80

90

90

70

80

90

90

90

Citric acid

10

10

10

10

10

10

10

10

Talc

10

10

10

10

10

10

10

10

10

Aerosil

20

20

20

20

20

20

20

20

20

Magnesium Stearate

90

60

30

10

90

60

30

10

10

Total Weight
in mg.

740

740

740

740

740

740

740

740

740

150

5751

--

Page

10

--

In vitro evaluations of floating tablet


Weight variation
Weight variation test was done according to USP.

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Vol 4, Issue 12, 2014.

Suchita Gulabrao Waghmare et al.

ISSN NO: 2231-6876

Tablet Hardness:
For each formulation, the hardness of 6 tablets was determined using the Monsanto hardness tester. (Cadmach).
Uniformity of Content:
Five tablets of each formulation were taken and amount of drug present in each tablet was determined. The individual
tablets were crushed and required amount of 0.1N Hydrochloric acid was added to extract the drug and volume was made up to 100
ml with 0.1N hydrochloric acid pH 1.2, filtered through whatman filter paper, 1 ml of filtrate were diluted to 10 ml with 0.1N
hydrochloric acid. The samples were analyzed in spectrophotometer at 276 nm.
Polymer Swelling or Water Uptake Studies:
The rate of test medium uptake by the polymer was determined by equilibrium weight gain method. The study was carried out
in the USP/NF dissolution apparatus I. The polymer matrices were accurately weighed placed in dissolution baskets, immersed in 0.1N
hydrochloric acid pH 1.2 and maintained at 370.5 0C in the dissolution vessels. At regular intervals, the pre weighed basket-matrix
system was withdrawn from the dissolution vessel, lightly blotted with a tissue paper to remove excess test liquid and re-weighed.
The percent water uptake, i.e. degree of swelling due to absorbed test liquid, was estimated at each time point using the
following equation:
Wt. of Swollen Tablet Initial Wt. of the Tablet
S.I. % = ----------------------------------------------------------------------------- 100
Initial wt. of the tablet
Floating Behavior
Floating Behavior studies were carried in a USP Dissolution Testing Apparatus II (paddle type) at paddle speed 50 rpm in
900 ml 0.1 N HCl at 370C for 12 h to mimic in vivo condition. The time interval between the introduction of the tablet into the
dissolution medium and its buoyancy to the top of dissolution medium was taken as buoyancy lag time the duration of system
floatation and also the relative matrix integrity was observed visually .
Floating lag time
This test was performed in beaker containing 200 ml 0.1 N HCl as a testing medium maintained at 370C. The time required
for the tablet to rise to the surface and float was determined as floating lag time .
Dissolution Studies
The release rate of Guaifenesin floating tablets was determined using USP Dissolution Testing Apparatus II (Paddle type).
The dissolution test was performed using 900 ml of 0.1N HCl, at 37 0.5C with 50 rpm. Aliquot (5 ml) of the solution was collected
from the dissolution apparatus hourly for 12 hours and were replaced with fresh dissolution medium. The aliquots were filtered
through Whatmann filter paper no. 41. Absorbance of these solutions was measured at 276nm. Aliquots were withdrawn at one hour
interval from a zone midway between the surface of dissolution medium and the top of rotating paddle not less than 1 cm apart from
the vessel wall. Cumulative percentage drug release was calculated using an equation obtained from a standard curve. Release studies
were performed in triplicate. Analysis of data was done by using PCP Disso V-3 software, India.
Drug release models
Drug release mechanisms and kinetics are the two important characteristics of a drug delivery system in describing drug
dissolution profile. To describe the kinetics of the drug release from tablet, mathematical models such as zero-order, first order,
Higuchi, Hixson-Crowell and Korsmeyer-Peppas models were used.
RESULT AND DISCUSSION
The tablet were prepared by direct compression method following extensive preformulation studies to select the appropriate
formulation components(mainly polymer) the two grades of HPMC(K100M and K15M) to provide sufficient swelling as well as drug
release retardation and sodium bicarbonate was selected as the suitable gas generating agent to reduce floating lag time to provide
sufficient buoyancy to the tablets.

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Drug polymer interaction studies by FTIR


Result shows that there was no incompatibility seen in between drug Guaifenesin and polymer (i.e. HPMC K100M) used, as
there was no significant change in the pattern of peaks of optimized batch with pure drug.

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Suchita Gulabrao Waghmare et al.

ISSN NO: 2231-6876

120

%T

105

90

75

60

45

30

15

4500
pure drug 2

4000

3500

3000

2500

2000

1750

1500

1250

1000

750

500
1/cm

Graph 1: FTIR spectra of pure drug.

25
0%
T
22
5
20
0
17
5
15
0
12
5
10
0
7
5
5
0
2
5
0
450
400
Drug + hpmc k
0
0
100 M

350
0

300
0

250
0

200
0

175
0

150
0

125
0

100
0

75
0

50
1/c
0
m

Graph 2: FTIR spectra of mixture of drug and hpmc K100M.


Evaluation of Floating tablet of Guaifenesin.

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Weight Variation
741.411.12
739.960.54
740.010.75
741.500.01
739.562.55
741.891.42
741.920.27
740.811.52
739.421.07

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Formulation Thickness Hardness Friability


F1
6.30.04
6.00.06 0.4440.08
F2
6.50.06
6.40.05 0.4530.10
F3
6.50.08
6.50.02 0.4320.14
F4
6.50.08
6.00.02 0.4280.04
F5
6.30.06
6.00.05 0.4310.11
F6
6.50.04
6.00.05 0.4260.11
F7
6.50.02
6.30.02 0.4280.09
F8
6.40.09
5.80.06 0.4520.12
F9
6.30.06
6.00.04 0.4420.08
*All the values are represents as Mean S. D. (standard deviation) (n=3)

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Table no.2

Vol 4, Issue 12, 2014.

Suchita Gulabrao Waghmare et al.

ISSN NO: 2231-6876

Table no.2 Swelling Index study.


Time (hrs)
Batch 3
6
9
F1
0.57 0.85 0.77
F2
0.59 0.86 0.78
F3
0.60 0.90 0.81
F4
0.61 0.92 0.82
F5
0.53 0.79 0.74
F6
0.56 0.83 0.76
F7
0.59 0.89 0.80
F8
0.60 0.91 0.80
F9
0.61 0.93 0.82
*All the values are represents as Mean S. D. (standard deviation) (n=3)

12
0.69
0.70
0.72
0.74
0.65
0.66
0.72
0.74
0.75

Graph no 3: swelling index of floating tablets.


The hydration ability of the polymer is important because it influences: (i) tablet buoyancy, (ii) adhesion ability of swellable
polymers as HPMC K15M, HPMC K100M in contact with the test fluid and (iii) drug release kinetics.Among all the batches the
greater swelling index i.e.0.93% was observed in F9 batch.
Table No. 3 Floating lag time and Buoyancy duration.
Buoyancy duration (hrs)
>10
>11
>11
>12
>9
>10
>10
>12
>12

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Floating lag time (sec)


210.14
220.02
180.04
160.02
250.09
210.06
200.02
160.04
180.06

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Formulation
F1
F2
F3
F4
F5
F6
F7
F8
F9

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Suchita Gulabrao Waghmare et al.

ISSN NO: 2231-6876

Table No. 4 In-vitro drug release study.


F1
0
21.26
37.10
55.66
64.03
73.07
84.40
90.54
99.56

F2
0
20.39
34.60
53.69
61.03
69.83
71.56
78.33
83.88
91.44
98.29

F3
0
22.12
28.00
34.08
39.69
46.34
52.66
59.16
64.94
71.22
77.49
82.74
87.05

F4
0
23.58
29.85
36.37
43.34
49.07
54.66
60.89
67.87
74.58
80.07
86.43
92.34

F5
0
21.59
36.38
54.81
63.31
73.91
84.98
92.32
99.63

F6
0
20.00
34.33
53.10
60.50
69.37
70.98
77.50
83.50
91.38
98.79

F7
0
18.60
25.29
30.73
36.17
42.13
47.69
52.81
88.63
65.07
70.43
74.34
78.39

F8
0
21.79
27.14
33.42
38.84
46.21
52.01
58.90
64.17
70.71
77.05
82.11
86.05

F9
0
21.26
26.02
31.45
36.69
41.61
46.85
52.42
56.97
62.22
67.28
73.90
79.01

Graph 5: Percent cumulative release of F5,F6,F7,F8,F9.

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Graph 4 :Percent cumulative release of F1,F2,F3,F4.

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Time(hrs)
0
1
2
3
4
5
6
7
8
9
10
11
12

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Suchita Gulabrao Waghmare et al.

ISSN NO: 2231-6876

Optimization of formulation
Analysis of the results obtained from formulation f4 concluded that the formulation containing HPMC K100M 300mg was
devised as optimized formula. Formulation F4 shows the satisfactory results in terms of flow property, friability, hardness, Floating
lag time, swelling index, Percent drug released. So formulation F4 is an optimized batch and chooses for further stability study. The
results of the various tests performed on this batch were as given in below
Table 5: Optimization parameters.
Sr. No.
1.
2.
3.
4.
5.
6.
7.
8.

Parameters
Appearance
Dimensions
Hardness
Weight variation
Ex- vivo Floating time
Ex-vivo Floating lag time
Surface pH
In-vitro drug release

Results
Good
Diameter:10.09 mm 0.1 mm
Thickness- 6.50.08
6.00.02 kg/cm2
Passes
More than 12 hrs.
160.02
57
92.34% in 12 hrs

Table 6: Kinetic model fitting of release data.


R2 values
Batch No.
F1
F2
F3
F4
F5
F6
F7
F8
F9

Zero order
0.996
0.994
0.954
0.908
0.995
0.973
0.925
0.913
0.888

First order
0.972
0.971
0.908
0.958
0.978
0.995
0.962
0.956
0.934

Higuchi
Model
0.967
0.964
0.995
0.996
0.966
0.964
0.997
0.993
0.994

Hixson-Crowell
0.995
0.992
0.941
0.944
0.997
0.993
0.952
0.944
0.92

Korsmeyar-Peppas
0.9911
0.9713
0.9760
0.982
0.9939
0.9712
0.89
0.9727
0.975

n value(release exponent(n)
0.784
0.786
0.453
0.457
0.778
0.793
0.5
0.458
0.417

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FUTURE SCOPE
Using the above formulation the drugs can be targeted to the specific region of body (stomach) in vicinity of absorption site.
All over the present investigation may put forth new areas for research and development and new formulation techniques to deal
with certain diseases in which drug residence time and bioavailability may be a problem of great concern.
To study in-vivo gastro retentive gamma-Scintigraphic.
To study in-vivo - in-vitro correlation (IVIVC).
To study the floating tablets prepared with different polymers and gas generating agents with different polymer combinations and
concentrations.
To study of floating concept and release of the drug at the stomach pH
To develop more cost affecting formation of Guaifenesin by using polymers. Which are cheap, easily available.
To carry out In-vivo study of optimized formulation and to determine various important pharmacokinetic such as T max , C max, AUC
To evaluate the floating performance of various polymers alone and in combination.
The floating concept can also be utilized in the development of various anti-reflux formulations.

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CONCLUSION
The present work showed that promising controlled-release floating matrix tablets of Guaiphenesin were successfully
formulated by effervescent technique.
Tablets containing HPMC K100M, NaHCO3 (formula F4) showed satisfactory results with respect to floating lag time, total
floating duration, swelling ability, and controlled drug release rates. Concentration and viscosity of polymer showed directly
proportional relationship with swelling characteristics of tablet. As viscosity and concentration of polymers increased, release rate of
drug was retarded. As the concentration of HPMC increases, percent drug release rate and floating lag time decreases. So it is
concluded that HPMC can act as floating enhancer. Drug release profiles on model fitting of optimized formulation F4 follows matrix
as best fit model which indicate that drug release is controlled by diffusion of drug through the pores.
Finally it was concluded that, the formulating stomach specific floating tablet of Guaifenesin by using direct compression
technique has been prepared successfully.

Vol 4, Issue 12, 2014.

Suchita Gulabrao Waghmare et al.

ISSN NO: 2231-6876

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