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WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
Nandvishal et al. World Journal of Pharmacy and Pharmaceutical Sciences
Volume 1, Issue 3, 1004-1015. Research Article ISSN 2278 – 4357
FORMULATION AND EVALUATION OF TERBUTALINE SULPHATE
Article Received on
08 August 2012,
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PULSATILE DRUG DELIVERY SYSTEM
Nandvishal V. Deore*, Vinod M. Thakare, Bharat W. Tekade, Vijay R. Patil.
TVES’s H.L.M.C. College of Pharmacy, Faizpur- 425503, Tal. Yawal Dist. Jalgaon,
Revised on 29 August 2012,
Accepted on 17 September2012
*Correspondence for
Author:
* Nandvishal V. Deore
TVES’s H.L.M.C. College of
Pharmacy, Faizpur- 425503,
Tal. Yawal Dist. Jalgaon,
Maharashtra, India.
nandvishal.deore@gmail.com,
vmthakre@gmail.com,
INTRODUCTION
ABSTRACT
Maharashtra, India.
Present research work was planned to developed a novel dosage form
using a chronopharmaceutical approach. A pulsatile dosage form,
taken at bedtime with a programmed start of drug release can prevent
a sharp increase in the incidence of asthmatic attacks, during the early
morning hours. The powedr blend was evaluated for pre compression
parameters. The pulsatile formulation was prepared by direct
compression method by using different concentrations of guar gum.
After that ten batches are selected and coated with enteric coated
polymer shellac. Prepared tablets were evaluated for post compression
parameters. Tablets were subjected to in-vitro drug release study in
1.2 pH and 7.4 pH. The formulation F8 shows significant behaviour
pattern compared with other formulations.
Key words: Terbutaline sulphate; Colon Delivery System; shellac.
In recent years, a considerable research activity in the field of colonic drug delivery has
occurred. Several prolonged release dosage forms are under investigation for delivery of
drugs to colon e.g. treatment of ulcerative colitis, Crohn's disease, colon carcinomas, for
systemic absorption of protein and peptide drugs. It is due to less hostile environment with
lesser diversity and intensity of enzymatic activities of colon as compared to stomach and
small intestine. (1) The anti-asthmatics targeted to colon for the treatment of nocturnal asthma
are systemically absorbed. It is also useful for delivery of insulin susceptible for degradation
by enzymes in upper gastrointestinal tract (GIT). The enzymatic activities associated with
microflora of colon can be used as a tool for colon specific drug delivery. In addition, colon
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has a longer retention time and appears to be highly responsive to agents that enhance the
absorption of poorly absorbed drugs. A colonic delivery system could be of absolute value
where delay in systemic absorption is therapeutically desirable, especially in the case of
diseases, which are affected by circadian rhythms. (2) A colon specific drug delivery system is
required to protect the drug during its transit through the upper gastrointestinal tract and to
allow its release in the colon. It is advantageous if drug release from a formulation can begin
immediately after it enter the colon, even though drug release may subsequently be retarded.
Drug release from ideal formulation should begin in the ascending colon, or a specified leg
time, at predetermined rate. Delivery of drug to the colon has implications in a number of
therapeutic areas. It includes local treatment of colonic disease like ulcerative colitis, colon
cancer, and inflammatory bowel disease.
There are various methods or techniques through which colon drug targeting can be achieved,
for example, formation of prodrug, coating with pH sensitive polymers, coating with
biodegradable polymers, designing formulations using polysaccharides, timed released
systems, pressure-controlled drug delivery systems, osmotic pressure controlled systems. (3,4)
Coating of the drugs with pH-sensitive polymers provides simple approach for colon-specific
drug delivery. The rationale of this study was to formulate and evaluate an oral pulsatile drug
delivery system containing terbutaline Sulphate, which can release the drug in pulsatile or
time dependent manner, to modulate the drug level in synchrony with the circadian rhythm of
asthma.
MATERIALS AND METHODS
Materials
Terbutaline sulphate was received as a gift sample from Shimoga Chemicals Pvt. India. Guar
Gum and shellac were gifted by Pure Chem Lab, Mumbai. Micro Crystalline Cellulose,
Dibutyl Phthalate and Sodium Starch Glycolate were received as gift samples from Loba
Chemicals Ltd, Mumbai and Signet Chemicals Ltd, Mumbai resp. All other ingredients were
laboratory grade.
Methods
Preparation of Colon specific pulsatile Tablet of Terbutaline Sulphate
Preparation of Core Tablet
The core tablets were prepared with selected excipients by direct compression on eight
station tablet compression machine. Accurately weighed quantities of drug and other
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Nandvishal et al. World Journal of Pharmacy and Pharmaceutical Sciences
excipients like sodium starch glycolate, guar gum, lactose, and magnesium stearate were
mixed by triturating in glass mortal and pestle. The blend was directly compressed by using
7 mm diameter punch. The compositions of the formulation batches containing different
ratios of polymers chosen on trial and error basis. (5) The Table No. 1 showed the ingredients
of core tablet.
Table 1: Formulation of Core Tablet
Formulation
Code
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Ingredient in %
TBS MCC SSG Guar gum Lactose Mg Stearate Talc
F1 8 60 2 15 54 4 2
F2 8 60 4 15 52 4 2
F3 8 60 6 15 50 4 2
F4 8 60 8 15 48 4 2
F5 8 60 2 20 47 4 2
F6 8 60 4 20 45 4 2
F7 8 60 6 20 43 4 2
F8 8 60 8 20 41 4 2
F9 8 60 2 25 44 4 2
F10 8 60 4 25 42 4 2
(Total weight of tablet was 145mg in each formulation from F1-F10)
Drug-polymer compatibility study
Drug polymer compatibility study was carried with FT-IR. The dry sample dug and polymer
was mixed by triturating with dry potassium bromide (A.R. Grade) and placed in sample cell.
The IR spectrum of the drug sample was recorded and the spectral analysis was done. (6)
Evaluation of Powder Mixture
Physical mixtures of different formulations were evaluated for angle of repose, bulk density,
tapped density, compressibility index and Hausner ratio. The angle of repose of was
determined by fixed funnel method. For determination of angle of repose (θ) the powder
mixture were poured through the walls of a funnel, which was set at a place such that its
lower tip was at a height of closely 2.0 cm above from ground surface. The powder mixture
were poured up to the time when upper tip of the pile surface touched the lower tip of the
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funnel. The tan¯ 1 of (height of the pile / radius of its base) give the angle of repose. Powder
mixtures were poured gently through a glass funnel into a graduated cylinder cut exactly to
10 ml mark. Excess powder mixture were removed using a spatula and the weight of the
cylinder with pellets required for filling the cylinder volume was calculated. The cylinder was
then tapped from a height of 2.0cm until the time when there was no more decrease in the
volume. Bulk density (ρb) and tapped density (ρt) were calculated. (7,8) Carr index (CI) were
calculated according to the equation which are follows:- CI= ρt- ρb/ ρt
Formulation of Coating Solution
Different coating formulations were prepared with various proportion of shellac, propylene
glycol, dibutyl phthalate and isopropyl alcohol was showed in Table No. 2.
Table 2: Formulation of Coating Solution
Coating of Tablets
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Coating Material CT 1 CT 2 CT 3 CT 4 CT 5 CT6
Shellac 4 6 8 4 6 8
% Wt Gain 1 2 3 4 5 6
Propylene Glycol 1 2 3 1 2 3
Dibutyl Phthalate 0.1 0.15 0.2 0.1 0.15 0.20
Isopropyl Alcohol 100 100 100 100 100 100
Different coating compositions were evaluated for Pulsatile drug delivery system of
Terbutaline sulphate. Tablets were coated with shellac polymer Coating solution in order to
retard the drug release from the compressed tablets in upper alimentary cannel. (9)
EVALUATION OF COATED TABLET
Thickness and Diameter of Tablets
Thickness permits accurate measurements and provide information on the variation between
tablets. Twenty tablets were taken for thickness measurment using a vernier-caliper. The
tablet thickness should be recline within a ±5% variation of a standard value. (10)
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Content of Uniformity
The TBS core tablets were tested for their drug content uniformity. At random 20 tablets
were weighed and powdered. The powder equivalent to 250 mg was weighed accurately and
mixed in volumetric flask containing phosphate buffer pH 7.4. Pass the solution through
Whatman filter paper No.41 for filtration. Then the serial dilution was carried out. The
absorbance of the solution was measured at 276 nm. The concentration of the drug was
computed from the standard curve of the Terbutaline sulphate in phosphate buffer pH 7.4. (11)
Disintegration Test
Disintegration test was carried out as described under procedure for uncoated tablets in USP.
One tablet each was placed in each of six tubes of the basket of the assembly. Apparatus was
operated using water, maintained at 37 ± 2 0 C as the immersion fluid. The time required for
complete disintegration was noted for each tablet. (12)
The In-Vitro Dissolution Study:
The In-Vitro dissolution studies of the pulsatile tablet formulation of Terbutaline sulphate
were carried out using dissolution test apparatus USP-II paddle type. The dissolution medium
consist of 900 mL of standard buffer of pH 1.2 for the first 2 hours, followed by pH 7.4 for
the remaining time period up to 8 to 10 hours. The temperature of the medium was
maintained at 37±0.5 0 C. The speed of rotation of the basket was kept at 75 rpm. Aliquots of 1
mL were withdrawn. These samples were diluted to make up the volume of 10ml with pH 1.2
buffer for first 2 hours and then by pH 7.4 buffer. The samples so withdrawn were replaced
with the fresh dissolution medium equilibrated at the same temperature. The drug released at
the different time intervals from the dosage form was measured by U.V. visible
spectrophotometer, by measuring the absorbance for the samples solutions at 272 nm (for pH
1.2) for Terbutaline Sulphate. (13)
RESULTS AND DISCUSSION
Preliminary Study
Drug-polymer Compatibility Study
The FT-IR spectra of pure drug was Scanning Range: 4000 – 400 cm –1 .
The same peaks may be shifted or merged but there were no such significant changes in the
IR peaks so we concluded that there was no such interpretation in between the drug and
polymers.
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Nandvishal et al. World Journal of Pharmacy and Pharmaceutical Sciences
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Figure 1: FT-IR Spectrum of Terbutaline Sulphate
Figure 2: FT-IR Spectrum of Optimized Coated Tablet
Physical Evaluation of Powder Blend used for Preparation for Core Tablet:
The powder blend was evaluated and the data was interpreted in Table No. 3
Table 3: Physical Evaluation of Powder Blend used for Preparation of Core Tablet
Formulation
Angle of
Repose
Bulk
Density
Tapped
Density
(Ѳ) (g/cm 2 ) (g/cm 2 ) Index
F1 28.670.12 0.3840.16 0.4340.14 11.520.22
%
Compressibility
F2 27.020.23 0.3770.12 0.4480.19 15.090.34
F3 27.780.33 0.3920.11 0.4460.14 13.650.17
F4 28.290.14 0.3770.16 0.4250.23 11.290.21
F5 30.710.48 0.3840.12 0.4250.24 9.640.16
F6 29.230.24 0.3770.18 0.4160.26 11.290.19
F7 28.930.23 0.3940.12 0.4440.21 11.710.23
F8 28.770.32 0.3630.15 0.4160.26 12.740.17
F9 28.320.24 0.3940.12 0.4340.15 9.210.15
F10 26.020.34 0.3920.14 0.4240.18 7.540.23
n= 3
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EVALUATION OF CORE TABLETS
Hardness and Friability
The tablets showed hardness values ranging from 3 to 4 kg/cm 2 . Another measure of a
tablet’s strength is friability. Conventional compressed tablets that lose less than 1% of their
weight are generally considered acceptable. In present study, the friability values for all the
tablet formulations were found to be

Nandvishal et al. World Journal of Pharmacy and Pharmaceutical Sciences
Table 4: Evaluation of Core Tablets
Form n
Code
Hardness
(kg/cm 2 )
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Weight
Uniformity
Friability
(%)
Thickness Uniformity
of Content
F1 3.6 142±0.158 0.552 1.51±0.15 99.77±0.73 655
F2 3.8 146±0.63 0.645 1.49±0.13 98.11±0.76 566
F3 3.9 144±0.65 0.549 1.38±0.13 99.10±0.89 405
F4 4.0 143±0.74 0.711 1.40±0.14 100.1±0.85 368
F5 4.1 147±0.59 0.398 1.55±0.15 98.77±0.81 298
F6 3.9 145±0.83 0.551 1.39±0.13 100.1±0.78 197
F7 4.0 144±0.67 0.701 1.45±0.13 101.0±0.72 227
F8 3.9 141±0.69 0.394 1.41±0.13 99.40±0.70 150
F9 3.8 148±0.76 0.575 1.26±0.14 100.1±0.74 174
F10 3.9 146±0.79 0.651 1.38±0.15 99.77±0.83 78
n=3
Dissolution Study
Table 5: In- Vitro Release Study of Coated Tablet Formulation F1 To F5
Time in
Min
% Cumulative Release/ hrs.
F1 F2 F3 F4 F5
0 0 0 0 0 0
30 0 0 0 0 0
60 0 0 0 0 0
90 0 0 0 0 0
120 0 0 0 0 0
150 14±1.31 1 0 0 0
180 94±1.61 20±1.58 0 0 0
210 96±1.28 90±1.86 12±1.91 0 0
240 - 95±1.01 85±1.47 18±2.13 0
270 - - 92±0.89 91±2.11 0
Disintegration
Time (Sec.)
300 - - - 96±1.61 17±1.88
330 - - - - 85±1.44
360 - - - - 94±1.13
390 - - - - -
n=3
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Table 6: In-Vitro Release Study of Coated Tablet Formulation F6 to F10
Time in
Min.
% Cumulative Release
120
100
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80
60
40
20
0
% Cumulative Release/ hrs.
F1-F5
0 100 200 300 400
Time in min
F6 F7 F8 F9 F10
0 0 0 0 0 0
30 0 0 0 0 0
60 0 0 0 0 0
90 0 0 0 0 0
120 0 0 0 0 0
150 0 0 0 0 0
180 0 0 0 0 0
210 0 0 0 0 0
240 0 0 0 0 0
270 0 0 0 0 0
300 0 0 0 0 0
330 78±2.14 4±3.11 0 0 0
360 93±1.79 90±1.52 0 0 0
390 96±1.67 93±1.25 9±2.35 9±2.25 9±2.15
420 - 95±1.13 93±2.22 92±2.12 91±2.32
450 - - 96±1.23 94±1.33 93±1.13
480 - - 98±1.23 - -
n=3
F1
F2
F3
F4
F5
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% Cumulative Release
120
100
80
60
40
20
0
The release profiles of Terbutaline Sulphate from the different formulation are shown in Fig.
No.5, 6 and Table No 5, 6. The data clearly indicate the drug release can effectively be
controlled by varying the concentration of polymer and Sodium Starch Glycolate.
Formulation F1 to F10 which contained Guar gum. This was due to increase concentration of
Sodium Starch Glycolate and decrease in concentration of Guar gum to give good drug
release. When a more concentrated polymer in the formulation resulted in slow release rate.
Formulations F1 to F10 release the total drug in up to 180-480min. Formulation F8 releases
the drug in 480 min with good drug release. The formulation F8 shows significant behavior
pattern compared with other formulations.
Scanning Electron Microscopy (SEM) Study
Coating layer of formulation of core tablet were examined for their surface morphology &
coating uniformity by using SEM (JEOL JSM-6300,JAPAN).
Figure 4: SEM Study of Coated Tablet F6
The coating of optimized batch were examined by scanning electron microscopy as shown in
figures 19, a illustrating the microphotographs of formulation F6 at higher magnification
(200X). The coated surface was spherical with no visible major surface irregularity.
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0 200 400 600
Time in min
F6-F10
F6
F7
F8
F9
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ACKNOWLEDGMENT
The authors are grateful to Shimoga Chemicals Pvt. India and Pure Chem Lab, Mumbai,
India for providing gift samples. The authors are thankful to TVES’S college of Pharmacy,
Faizpur for providing necessary facility to carry out this research.
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