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Int. J. Chem. Sci.: 9(2), 2011, 664-672
ISSN 0972-768X
www.sadgurupublications.com
FORMULATION AND EVALUATION OF CIPROFLOXACIN
DISPERSIBLE TABLETS USING PLANTAGO OVATA
MUCILAGE IN COMPARISON WITH OTHER
SUPERDISINTEGRANTS
P. ANUSHA, B. V. BASAVARAJ*, S. BHARATH, R. DEVESWARAN and
V. MADHAVAN
M. S. Ramaiah College of Pharmacy, M. S. R. Nagar, M. S. R. I. T. Post,
BANGALORE – 560 054 (K.S.) INDIA
ABSTRACT
In the present work, an attempt has been made to study the superdisintegrant property of isolated
mucilage powder of Plantago ovata by formulating the dispersible tablets of ciprofloxacin and comparing
its efficiency with other super disintegrants like microcrystalline cellulose, crosspovidone and sodium
starch glycollate. Drug compatibility with the mucilage was checked by FTIR studies and found to be
intact and stable. The values of pre-compression and post-compression parameters evaluated were within
the prescribed limits and showed good flow property. In all the formulations, friability was less than 1%,
indicating that tablets had a good mechanical resistance. Drug content and weight variation for all the
formulations were found to be within the acceptable limits. The formulations were also evaluated for
wetting time, hardness, thickness, disintegration time, uniformity of dispersion, water absorption ratio and
dissolution. The results of all the tests of the formulation prepared with Plantago ovata mucilage powder
are similar to that of those formulations prepared using other superdisintegrants and the disintegration time
was found to be 110 sec. The study also revealed that the isolated mucilage powder of Plantago ovata
showed a better drug release of 99% over the other superdisintegrants, sufficing its applications as a
superdisintegrant of natural origin.
Key words: Dispersible tablets, Plantago ovata mucilage, Synthetic super disintegrants.
INTRODUCTION
Tablet is the most popular dosage form among all existing today because of
convenience of self administration, compactness and easy manufacturing. Convenience of
Int. J. Chem. Sci.: 9(2), 2011 665
administration and patient compliance are gaining importance in design of various dosage
forms. This concept oriented research has resulted in bringing out many safer and newer
drug delivery systems1.
Dispersible tablets are intended to dissolve or disintegrate rapidly in the mouth for
which various disintegrants either natural or synthetic are included in the formulation2. They
are uncoated tablets that produce a uniform dispersion in water at room temperature without
stirring. They are easier to swallow than capsules for pediatric, dysphasic patients, mentally
ill, unco-operative and nauseated patients, those with conditions of motion sickness, sudden
episodes of allergic attacks or coughing3.
Mucilage is most commonly used as excipient in the manufacturing of various
pharmaceutical dosage forms. Mucilages of natural origin are preferred over semi-synthetic
and synthetic because of their non-toxic, low cost, free availability, emollient and non-
irritating nature4.
Mucilage of Plantago ovata seeds has various characteristics like binding,
disintegrating and sustaining properties5. This is also used as suspending and thickening
agent because of its high swelling factor and ability to form viscous solution6.
Ciprofloxacin is a synthetic quinolone derivative. It is widely prescribed because of
its safety, good tolerance and broad antibacterial spectrum7.
EXPERIMENTAL
Materials and method
Ciprofloxacin was procured from Yarrow Chem Products, Mumbai. Isapghula seeds
were purchased from local market. All others excipients used are of analytical grade.
Isolation of mucilage
The seeds were soaked in distilled water (20-30 times) for at least 48 hrs8. Then the
seeds boiled for few minutes for complete release of mucilage into water. The material was
filtered by squeezing in a muslin cloth to remove marc. Then equal volume of acetone was
added to filtrate to precipitate the mucilage. The mucilage was separated and dried in an
oven at a temperature less than 60ºC, powdered, sieved (# 80 mesh), weighed and stored in
desiccator until further use9.
P. Anusha et al.: Formulation and Evaluation of….
666
Formulation of dispersible tablets
The dispersible tablets of ciprofloxacin were prepared by non-aqueous wet
granulation method using absolute alcohol as the solvent. Plantago ovata mucilage powder,
microcrystalline cellulose, sodium starch glycollate, crosspovidone were used as
disintegrants, dicalcium phosphate as a diluent, PVP as a binder, aspartame as sweetener,
purified talc as lubricant and aerosil as glidant (Table 1). The drug and other ingredients
with half the quantity of disintegrant (intragranular disintegrant) were mixed together,
sufficient quantity of alcohol was added and mixed to form a coherent mass. The wet mass
was granulated using sieve No. 12 and the coarse granules formed were dried in a tray dryer
(Tempo instruments and equipments, Mumbai) at 40oC for 20 minutes and regranulated
through sieve No. 18. The granules were further blended with the remaining quantity of the
disintegrant (extragranular disintegrant), purified talc, aerosil and compressed into tablets
using a 8 mm round concave punches in a rotary tablet machine 5 (Rimek, RSB-4 mini press
Cadmach, Ahmedabad, India).
Table 1: Composition of different batches of ciprofloxacin tablets
Ingredients F1 (mg) F2 (mg) F3 (mg) F4 (mg)
Ciprofloxacin 100 100 100 100
Dicalcium phosphate 100 100 100 100
Isapghula mucilage powder 25 - - -
Microcrystalline cellulose - 25 - -
Crosspovidone - - 25 -
Sodium starch glycollate - - - 25
Poly vinyl pyrrolidone 15 15 15 15
Purified talc 3 3 3 3
Aspartame 5 5 5 5
Aerosil 2 2 2 2
Drug-mucilage interaction studies
The physical mixture of pure drug sample and isolated mucilage powder in the ratio
Int. J. Chem. Sci.: 9(2), 2011 667
1 : 1 were subjected to IR spectral studies using FTIR spectrophotometer (FTIR 8400 S,
Shimadzu, Japan).
Evaluation of the tablets
Pre-compression parameters
The granules were studied for various micromeritic properties such as angle of
repose, bulk density, tapped density, Carr’s index and Hausner’s ratio.
Post-compression parameters
Weight variation
Randomly twenty tablets were selected after compression and the mean weight was
determined. The sample tablets were weighed individually and the deviation from the mean
weight was calculated (USP XXVII).
Thickness variation
Ten tablets from each formulation were taken randomly and their thickness was
measured with a micrometer screw gauge.
Hardness
The crushing strength of the tablets was measured using a Monsanto hardness tester.
Six tablets from each formulation batch were tested randomly and the average reading
noted.
Friability
Twenty tablets were weighed and placed in a Roche friabilator and rotated at 25 rpm
for 4 min. The tablets were taken out, dusted and reweighed. The percentage friability of the
tablets was calculated by the formula,
Percentage friability =
Initial weight - Final weight
Initial weight
× 100
Drug content
Twenty tablets were weighed and powdered. An amount of the powder equivalent to
100 mg of ciprofloxacin was dissolved in 100 mL of 0.1 N HCl filtered, diluted suitably and
estimated for the drug content at 277.5 nm using UV-Visible spectrophotometer (UV 160-
Shimadzu, Japan).
P. Anusha et al.: Formulation and Evaluation of….
668
Wetting time and water absorption ratio (R)10
Twice folded tissue paper was placed in a Petri dish having an internal diameter of
5 cm containing 6 mL of water. A tablet was carefully placed on the surface of the tissue
paper in the Petri dish. The time required for water to reach the upper surface of the tablet
and to completely wet it was noted as the wetting time.
Water absorption ratio (R) was then determined according to the following equation:
R = 100 × (wa – wb)/wb
Where wb and wa were tablet weights before and after water absorption,
respectively.
In-vitro disintegration time
In vitro disintegration time was measured by placing a tablet in 100 mL water
maintained at 25oC. The time taken for the tablet to disintegrate completely was noted.
Uniformity of dispersion
Two tablets were placed in 100 mL of water and stirred gently until completely
dispersed. A smooth dispersion was obtained which passed through a sieve screen with a
nominal mesh aperture of 710 mm (sieve number 22).
In-vitro dissolution study
In-vitro drug release studies of all the formulations were carried out using multi
basket tablet dissolution test apparatus (USP TDT 06 PL, Electrolab, Mumbai) at 50 rpm.
0.1 N HCl was used as the dissolution media with temperature maintained at 37 ± 1oC.
Samples were withdrawn at different time intervals, diluted suitably and analyzed at 277.5
nm using Shimadzu UV-Visible spectrophotometer7.
RESULTS AND DISCUSSION
The reported isolation method yielded 30% of mucilage powder from the seeds of
Plantago ovata. Dispersible tablets each containing 100 mg of ciprofloxacin were prepared
employing mucilage powder of Plantago ovata, microcrystalline cellulose, crosspovidone
and sodium starch glycollate using non-aqueous wet granulation method (Table 1). The drug
excipient interaction was studied by FTIR spectroscopy revealed that the drug was stable
and intact in the mixture without any change in the principle peaks of the drug (Fig. 1).
Int. J. Chem. Sci.: 9(2), 2011 669
40
60
80
100
%T
3946.09
37 76 .36
3726.22
369 5.3 6
3004.89
2947.03
2896.88
2345.28
2318 .28
2237.27
2052.12
1994.2 6
1893.97
1851.54
182 4. 53
1708.81
1485.09
1454.23
13 80. 94
1342.36
1315.36
126 9.0 7
1 230 .50
1184.21
1037.63
98 3. 63
948.91
840 .91
821.62
470.60
70
80
90
100
%T
3938 .37
3791.79
3726.22
3664.50
2974.03
2947.03
2877.60
2711.73
2615.29
2503.43
2468.7 1
241 8.5 7
2399.28
2329.85 2260.42
2144.70
2094.55
2032 .83
1982 .69
1913.25
176 6. 67
1353.94
130 7.6 5
1269.07
1253.64
1222.79
1172.64
1041.4 9
979.77
952 .77
898 .77
802.33
40060080010001200140016001800200024002800320036004000
1/cm
25
50
75
100
%T
30 70. 4 6
3008.75
2974.03
290 0.7 4
2839.02
2761.87
2707 .87
26 19. 15
2499.57
2464.86
2329.85
2133.12
20 67 .55
1623 .95
1 550 .6 6
1384.79
1342.36
1311.50
1168 .78
1149 .50
983.63
95 6.63
89 4.91
852.48
806.19
779.19
671.18
64 8.04
559.32
447.45
408.8 8
Fig. 1: FTIR spectra of drug, mucilage and the physical mixture
P. Anusha et al.: Formulation and Evaluation of….
670
The values of pre-compression parameters evaluated were within prescribed limits
and indicated good free flowing property as given in (Table 2).
Table 2: Pre-compression parameters of powder blend
The data obtained from post-compression parameters in all the formulations,
friability was less than 1%, indicated that tablets had a good mechanical resistance. Drug
content was found to be in the range of 97.88 to 100.2%, which is within acceptable limits.
Hardness and thickness of the tablets were found to be in the range of 2.50-3.50 kg/cm2 and
3.5-3.75 mm respectively. Water absorption ratio and wetting time of F1 was found to be
32% and 60 sec and for other formulations were found to be in the range of 26-52% and 59-
87 sec respectively. The disintegration time for F1 was found to be 110 sec and for other
formulations it is in the range of 49-290 sec (Table 3).
Table 3: Post-compression parameters of dispersible tablets of ciprofloxacin
Parameter F1 F2 F3 F4
Weight variation (mg) 0.25 ± 0.01 0.257 ± 0.01 0.257 ± 0.01 0.25 ± 0.01
Thickness (mm) 3.75 3.70 3.64 3.56
Hardness (Kg/cm2) 3.0 3.5 2.5 2.5
Friability (%) 0.49 0.4 0.38 0.77
Drug content (%) 97.88 99.9 100.2 99
In vitro disintegration time (sec) 110 290 49 180
Wetting time (sec) 60 87 59 67
Water absorption ratio (%) 32 52 36 26.9
Uniformity of dispersion Passes Passes Passes Passes
Formulation
code Angle of
repose (o) Bulk density
(gm/cc) Tapped density
(gm/cc) Carr’s
index (%) Hausner’s
ratio
F1 26.74 0.57 0.65 12.30 1.14
F2 25.96 0.575 0.65 12.30 1.130
F3 28.73 0.45 0.52 13.4 1.15
F4 27.29 0.535 0.605 11.5 1.130
Int. J. Chem. Sci.: 9(2), 2011 671
The drug release for F1 was found to be 99.8 % within 15 min and for other
formulations it was released in 20 min except for F2 with 95 % drug release at 45 min
(Table 4). It was very much clear that F1 exhibited better disintegration and dissolution
behaviour suited for a dispersible tablet compared to other super disintegrants.
Table 4: In vitro release studies of different formulations
Formulation
code D5
(%) D10
(%) D15
(%) D20
(%) D25
(%) D30
(%) D35
(%)
D40
(%) D45
(%)
F1 55.49 83.60 99.8 - - - - - -
F2 13.51 29.08 44.09 56.98 72.51 81.31 86.63 92.75 95.75
F3 71.99 89.86 93.29 97.84 - - - - -
F4 57.65 84.70 94.77 97.62 - - - - -
Where Dx (%) = % of drug released in respective min.
F1
F2
F4
F3
Time (min)
% Drug release
100
80
60
40
20
00 10 20 30 40 50
Fig. 2: Dissolution profile of all formulations
CONCLUSION
The isolated mucilage of Plantago ovata proved to be better super disintegrant for
dispersible tablets in comparison with synthetic superdisintegrants. The mucilage evaluated
for various physico-chemical parameters, showed the same characteristic similarities with
the other established superdisintegrants. Hence Plantago ovata mucilage of natural origin
could be successfully employed as superdisintegrant in the formulation of dispersible tablets.
P. Anusha et al.: Formulation and Evaluation of….
672
REFERENCES
1. A. Prameela Rani, N. Archana, P. Siva Teja, P. Mohan Vikas, M. Sudheer Kumar and
C. Bala Sekaran, Int. J. Appl. Pharma., 2(3), 15 (2010).
2. R. Deveswaran, Sharon Furtado, S. Bharath, Sindhu Abraham, B. V. Basavaraj and V.
Madhavan, Arch. Pharm. Sci. Res., 2(1), 230 (2010).
3. B. S. Kuchekar, S. R. Pattan, R. K. Godge, R. B. Laware, S. A. Nirmal, S. K. Parjane
and A. N. Merekar, J. Chem. Pharm. Res., 1(1), 336 (2009).
4. S. B. Shirsand, Sarasija Suresh, M. S. Para, M. S. Swamy and D. Nagendra Kumar,
Indian J. Pharm. Sci., 71(1), 41 (2009).
5. N. G. Raghavendra Rao, Upendra Kulkarni, K. Durga Rao and D. K. Suresh, Int. J.
Pharmacy Pharm. Sci., 2, 70 (2010).
6. S. Shanmugam, R. Manavalan, D. Venkappayya, K. Sundaramoorthy, V. M.
Mounnissamy, S. Hemalatha and T. Ayyappan, Nat. Pro. Rad., 4(6), 478 (2005).
7. J. Mu’az, L. K. Gazali, G. U. Sadiq and G. M. Tom, Nig. Jour. Pharm. Sci., 8(2), 102
(2009).
8. M. A. Tahir, K. Awadhesh, S. Swati, S. Sant, M. A. Sajid, G. D. Pattnaik and Farheen,
Int. J. Ph. Sci., 2(2), 496 (2010).
9. N. G. Raghavendra Rao, Thube Ketan and Sumanji Bala, Int. J. Pharm. Cli. Res., 2(1),
40 (2010).
10. Nikku D. Yadav, Prashant L. Pingale and Sagar R. Tatane, J. Pharm. Res., 3(7), 1594
(2010).
Accepted : 21.02.2011
