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ABSTRACT
The present work was aimed at formulation development, evaluation and comparative study of the effects of
superdisintegrants in Cefixime 50 mg oral disintegrating tablets. The superdisintegrants used for the present study
were sodium starch glycolate and crosscarmellose sodium. The formulated tablets were evaluated for various
tableting properties, like hardness, thickness, friability, weight variation, disintegration time and dissolution rate.
Comparative evaluation of the above-mentioned parameters established the superiority of the tablets formulated
with crosscarmellose sodium to those formulated with sodium starch glycolate.
DOI: 10.4103/0975-1483.66794
Cefixime trihydrate was procured from Aurobindo Pharma Accurately weighed quantity of powder is introduced
Ltd . Sodium starch glycolate and croscarmellose sodium into a measuring cylinder. Mechanically tap the cylinder
were procured from DK Enterprises, while magnesium containing the sample by raising the cylinder and allowing
stearate and talc was from Nice Chemicals . it to drop under its own weight using a suitable mechanical
tapped density tester at a nominal rate of 300 drops/min.
Methodology Tap the cylinder 500 times and measure the tapped volume
(Va). Repeat the operation for an additional 750 tappings
Preformulation studies[5-7] and again measure the tapped volume as (Vb).
Preformulation study is defined as an investigation of
the physical and chemical properties of drug substance If the difference between Va and Vb is <2%, Vb is the final
alone and when combined with the excipients. The tapped volume (Vf). If the difference is higher, repeat the
overall objective of preformulation testing is to generate tapings for an additional 1,250 times, and then the tapped
information useful to the formulator in developing a stable density can be calculated using the following formula
and bioavailable dosage form that can be mass produced. (United States pharmacopoeia, 2004)
The commonly investigated preformulation parameters
include angle of repose, bulk density/tapped density, pour Tapped density = M/Vf
density, Carr’s compressibility index and Hausner ratio.
Where, M = weight of the sample taken; Vf = final tapped
Angle of repose volume
It is determined by allowing a powder to flow through
a funnel and fall freely on to a surface. Further addition Carr’s index
of powder is stopped as soon as the pile touches the tip
of the funnel. A circle is drawn around the pile without The compressibility index of granules can be determined
disturbing it. The height and diameter of the resulting cone using Carr’s compressibility index, and can be determined
are measured. The same procedure is repeated three times by the following formula:
and the average value is taken. Angle of repose is calculated
by using the following equation: (Tapped density –
Pour density)
Tan θ = h/r Carr’s index (%) = X 100
Tapped density
Where, h = height of the powder cone; r = radius of the
powder Hausner ratio
Bulk density The Hausner ratio can be determined using the following
formula:
Unless otherwise specified, pass a quantity of material
sufficient to complete the test through a 1.00-mm (no. 18) Tapped density
screen to break up agglomerates that may have formed Hausner ratio (%) = X 100
during storage. Into a dry 250-ml cylinder introduce, without Pour density
compacting, approximately 100 g of the test sample (M)
Compatibility studies
weighed with 0.1% accuracy. If it is not possible to use
100 g, the amount of the test sample and the volume of IR studies of drug and drug with superdisintegrants were
the cylinder may be modified. Select a sample mass having carried out in order to check the compatibility between the
an untapped apparent volume of 150–250 ml. A 100-ml drug and the excipients.
cylinder is used for apparent volumes between 50 and 100
ml. Fill the cylinder carefully. Carefully level the powder Formulation development
without compacting, if necessary, and read the unsettled
apparent volume (Vo). Calculate the bulk density, in g/ml, The methodology selected for the preparation of cefixime
using the formula, oral disintegrating tablets is direct compression. About 10
J Young Pharm Vol 2 / No 3 235
Remya, et al. J Young Pharm. 2010;2(3): 234-239
formulations were prepared, of which five formulations Six tablets were evaluated to determine the average
included varying concentrations of the superdisintegrant thickness.
sodium starch glycolate and five of crosscarmellose
sodium. The list of ingredients is given in Tables 1 and 2. Disintegration test
Tablet evaluation[8-10] Introduce one tablet into each tube and add a disc to each
tube. Suspend the assembly in the beaker containing the
The selected batches made in bulk were subjected to specified liquid and operate the apparatus for a specified
evaluations as per Indian pharmacopoeia. period of time. The tablet passes the test if all tablets have
disintegrated. If one or two tablets fail to disintegrate,
Weight variation repeat the test on 12 additional tablets, such that not <16
of the total of 18 tablets tested disintegrate. If the tablets
Twenty tablets were selected at random, weighed and the
adhere to the disc, repeat the test by omitting the disc. The
average weight was calculate. Not more than two of the
preparation complies with the test if all the tablets in the
individual weights should deviate from the average weight
repeat test disintegrate.
by more than 5%.
Dissolution studies/in vitro release studies
Friability
Table 3: Physicochemical evaluation of the known concentration of USP cefixime reference standard
formulations (RS) in the same medium.
Parameters Formulation with Formulation with
cross carmellose sodium starch
mean value of glycollate RESULTS AND DISCUSSION
(C1 – C5) (S1 – S5)
Angle of repose 24 ° 37’ 2.1’’ 27° 25’ 13.02’’
Preformulation studies
Bulk density / tapped 0.6517 0.7117
density
Pour density 0.5140 0.5761 Values of the preformulation studies are given in Table 3,
Carr’s compressibility index 21.12 19.05 from which it is evident that all the parameters analyzed
Hausner ratio 1.26 1.23 showed satisfactory flow properties and compression
characteristics.
Table 4: Tablet ingredients for scale up batch Compatibility studies
Ingredients Quantity/ Quantity Quantity
tablet (mg) for 50 for 50
tablets (g) tablets (g) IR spectra of cefixime, sodium starch glycolate,
(S3) (C 1) crosscarmellose sodium and combinations are given in
Cefixime trihydrate 55.90 2.795 2.795 Figures 1–5. The results of the FTIR spectral analysis
Microcrystalline 214.30 10.715 10.715
cellulose
showed that the peaks and the pattern of the spectra
Sodium starch glycolate 5.60 0.280 ---- were similar in all cases, which indicated that there was no
Cross carmellose sodium 5.60 ---- 0.280 chemical interaction or decomposition of cefixime during
Magnesium stearate 1.40 0.070 0.070 the preparation of the tablets.
Talc 2.80 0.140 0.140
Pineapple flavor q.s q.s q.s Formulation
Tarazarine lake q.s q.s q.s
Average weight (mg) 280.00 ---- ---- Because the aim of the project was to formulate cefixime
50 mg DT tablet, which disintegrated within 1 min, priority
Table 5: Evaluation parameters of the best was given so as to get good results with cost-effectiveness
formulations of the product.
Tablet evaluation Formula S3 Formula C1
parameters
From the tables and histograms, it was evident that the
Diameter 0.96 0.95
Thickness 0.36 0.38
formulations C1 and S3 stood ahead in all the tableting
Hardness 3.0 3.5 properties and in disintegration performance. Both the
Friability 0.751 0.725 batches were prepared in bulk [Table 4] and confirmatory
Weight variation pass pass evaluation tests were carried out.
Disintegration time (sec) 42 32
Dissolution rate (%) 94.56 96.37 DT stands satisfactory with the time limit of <1 min for all
100
%T
100
95 %T
95
2401.21
90
90
2491.86
2696.30
2758.02
709.76
2613.37
85
85
1263.29
2854.45
1224.71
80 80
3544.92
2850.59
2929.67
2947.03
1325.01
3082.04
3137.97
75
1421.44
75
3124.47
1382.87
2918.10
3186.18
3153.40
1535.23
3190.04
1546.80
1157.21
3298.05
70
70
1751.24
1598.88
1587.31
1112.85
3494.77
3461.99
3382.91
1020.27
65
1060.78
1664.45
65
60
60
1764.75 4000 3750 3500 3250 3000 2750 2500 2250 2000 1750 1500 1250 1000 750 500
Cross carmilos Na 1/cm
55
4000 3750 3500 3250 3000 2750 2500 2250 2000 1750 1500 1250 1000 750 500
Cefixime 1/cm
100
100 %T
97.5
%T
95 95
92.5
2931.60
90
707.83
90
2916.17
576.68
1766.67
85 87.5
1664.45
1427.23
1598.88
85
3407.98
80
3255.62
1103.21
82.5
1164.92
1155.28
3394.48
1080.06
1114.78
75 80
997.13
1060.78
77.5
70
1026.06
1016.42
75
65
4000 3750 3500 3250 3000 2750 2500 2250 2000 1750 1500 1250 1000 750 500 4000 3750 3500 3250 3000 2750 2500 2250 2000 1750 1500 1250 1000 750 500
NaStarch Glycolate 1/cm formula 1 1/cm
Figure 3: IR spectrum of sodium starch glycollate Figure 4: IR spectrum of cefixime tablet blend with crosscarmellose
sodium
100
%T
Time in seconds
90
80
80
60
40
70
2902.67
3139.90
1427.23
60
20
1321.15
0
3201.61
50
1163.00
S1 S2 S3 S4 S5
3274.90
40
1112.85
3384.84
Formulations
1058.85
30
1020.27
20
4000 3750 3500 3250 3000 2750 2500 2250 2000 1750 1500 1250 1000 750 500
formula 2 1/cm
Figure 5: IR spectrum of cefixime tablet blend with sodium starch Figure 6: Disintegration profile of the selected batch
glycolate
the batches, as shown in Figures 6 and 7. Now, the question Evaluation of tableting properties of the selected batches
exists for fixing the best batch among the rest. Hence, for confirm the standards prescribed in Indian pharmacopoeia.
the comparative study, one with the same percentage was The results are given in Tables 6 and 7.
selected (2%). The batches S3 and C1 were selected to carry
out further evaluation [Table 5]. Disintegration time was found to be within 1 min and