Singapore Journal of Pharmaceutical Research
Singapore Journal of Pharmaceutical Research
Singapore Journal of Pharmaceutical Research
e - ISSN – XXXX-XXXX
Print ISSN - XXXX-XXXX
Singapore Journal of Pharmaceutical Research
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Brahmaiah Bonthagarala. et al. / Singapore Journal of Pharmaceutical Research. 2014;1(1):1-7.
There are number of techniques applied in the The powders were evaluated for angle of repose,
formulation and manufacturing of sustained release dosage loose bulk density, tapped bulk density, compressibility
form. However, matrix tablet prepared by direct index, total porosity etc.
compression method has attracted much attention due to its
technological simplicity in comparison with other Bulk density
controlled release systems. Direct compression method had LBD (Loose Bulk Density) and TBD (Tapped
been applied for preparation of matrix tablet that involved Bulk Density) were determined by 2g of powder from each
simple blending of all ingredients used in the formulations formula. The powder was previously lightly shaken to
and then underwent direct compression. It required fewer break any agglomerate formed and then it was placed into a
unit operations, reduced number of personnel and reduced 10 ml measuring cylinder. After the initial volume was
processing time, increased product stability and faster observed, the cylinder was allowed to tap under its own
production rate [6]. There are three primary mechanisms by weight onto a hard surface from the height of 2.5 cm at 2
which active agents can be released from a delivery system: second intervals. The reading of tapping was continued
diffusion, degradation, and swelling followed by diffusion. until no further change in volume was noted. Using the
The release of drug from the matrix tablet depends on the following equation LBD and TBD was calculated LBD =
nature of polymer. HPMC K4M, HPMC K15M CR and Weight of the powder / bulk volume of the packing. TBD =
HPMC K100LV CR are hydrophilic polymers that become Weight of the powder / Tapped volume of the packing. The
hydrated, swollen and facilitates to diffuse the drug [7]. The results were shown in Table 2.
effect of hydrophilic polymer PEG 6000 which act as a
channeling agent was evaluated on the matrix tablet with Compressibility index
combination of HPMC K4M. Here Ph independent swelling The compressibility index of the granules was
of Eudragit RSPO and Eudragit RLPO released the drug determined by Carr’s Compressibility index [8]. The results
from the matrix. In the present study an attempt had been were shown in Table 2.
made to formulate Ozcarbazepine as sustained release Carr’s index (%) = {(TBD – LBD) X 100}/TBD
matrix tablet with the addition of release retarding polymers
HPMC E 50 LV, Eudragit RSPO. Angle of repose
The angle of repose of granules was determined by
MATERIALS & METHODS the funnel method [9]. The results were shown in Table 2.
Ozcarbazepine, Eudragit RSPO, HPMC E 50LV,
Avicel and magnesium stearate, were obtained and used as Hausner’s Ratio
received. All other chemicals and solvents used were of It is the frictional resistance of the drug .The ideal
analytical grade. range should be 1.2-1.5. It is determined by the ratio of
tapped density and the bulk density [10]. The results were
Preparation of Matrix Tablets by Direct Compression shown in Table 2.
Method
Ozcarbazepine drug was used with various types Formula:
of polymers (HPMC, Eudragit RSPO) in varying ratios to Hausner’s ratio= Vi/Vt
formulate the sustained release matrix tablets. Avicel 102 Where, Vt is the tapped volume
was used as a diluent in the preparation of the tablets. Vi is the untapped volume
Magnesium stearate (1% w/w) was added in the
formulation as a lubricant. The tablet weight (404 mg) was EVALUATION OF TABLETS
adjusted so as to contain 200 mg of Candidate drug in each Weight Variation
tablet. The Ozcarbazepine sustained release matrix tablets Twenty tablets were randomly selected from each
were prepared by passing drug, Polymers, Avicel 102 batch and individually weighed. The average weight and
through a #30 mesh sieve. Finally adds a Magnesium standard deviation of 20 tablets was calculated. The batch
stearate by passing through the #60 mesh sieve. The blend passes the test for weight variation test if not more than two
was compressed in a Cadmach tablet compressing machine of the individual tablet weight deviates from the average
fitted with concave punches (14.5 mm × 4.5 mm).Finally weight by more than the percentage shown in Table 3 and
the tablet weight was adjusted to 400mg. none deviate by more than twice the percentage shown
[11].
Pre formulation studies
The parameters like identification of pure drug Thickness
Ozcarbazepine by IR spectra, drug excipients compatibility Three tablets were randomly selected from each
studies, angle of repose, bulk density, tapped density, batch and there thickness was measured by using vernier
Hausner‘s ratio, Carr’s index. calipers. Thickness of three tablets from each batch was
measured and mean was calculated. The results were shown
Physical evaluation of powders in Table 3.
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Brahmaiah Bonthagarala. et al. / Singapore Journal of Pharmaceutical Research. 2014;1(1):1-7.
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Brahmaiah Bonthagarala. et al. / Singapore Journal of Pharmaceutical Research. 2014;1(1):1-7.
showing only 38.9% of drug release in 24 hours with very plots were found to be 0.919, 0.891, 0.988, 0.965, and
slower release. In case of tablets of F4, containing drug and 0.919 respectively. The ‘n’ value for F8 was found to be
Eudragit RSPO, HPMC E50 LV in the ratio 1.25:1 the 0.735 which is indicates that the release approximates non-
release profile was showing only 52.64% of drug release in fickian diffusion mechanism. The regression coefficient of
24 hours with very slower release. In case of tablets F5, formulation F8 was found to be 0.919. These results
containing drug and Eudragit RSPO, HPMC E50 LV in the indicated that the release rate was limited by the drug
ratio 1:1.25 the release profile was showing only 79.38% of particles dissolution rate and erosion of the polymer matrix.
drug release in 24 hours with slower release. In case of The In-vitro drug release profile of tablet from each batch
tablets F6, containing drug and Eudragit RSPO, HPMC (F1 to F10) was carried out and results are shown in Table
E50LV in the ratio 1:2 the release profile was showing only No 5. Thus, it may be concluded that the drug release from
86.38% of drug release in 24hours with slower release. But sustained release matrix tablet of Ozcarbazepine is best
it was observed that release rate was increased when the explained by Higuchi Kinetic model. The values of slope
concentration of Eudragit RSPO polymer concentration was and intercept for Higuchi Kinetic model are 0.988 and
decreased. In case of tablets of F7, containing drug and 21.80 respectively
Eudragit RSPO & HPMC E50 LV in the ratio 1:3.5 the The optimized formulation of Sustained release
release profile was showing 100 % of drug release in 24 matrix tablets of Ozcarbazepine tablets were subjected to
hours. But it was observed that release rate was not accelerated stability studies. Stability studies of the
matched with the USP results. In case of tablets F9, optimized formulation were performed at ambient humidity
containing drug and Eudragit RSPO, HPMC E50 LV in the conditions, at room temperature, at 40 oc ± 2oC &75% RH
ratio 3.5:1 the release profile was showing only 37.22% and 2-8oc for a period up to 30 days. The samples were
drug release in 24 hours, The dissolution study was shown withdrawn after periods of 15 days, and 30 days and were
that Eudragit RSPO, HPMC E50 LV in 3.5:1 ratios more analyzed for its appearance, hardness, friability, drug
controlled the release of drug from formulation. In case of content and in vitro drug release. The results obtained were
tablets of F10, containing drug and Eudragit RSPO & shown in Table 6-8.The results revealed that no significant
HPMC E50 LV in the ratio 8:1 the release profile was changes in appearance, drug content, hardness, friability,
showing 35.94 % drug release in 24 hours. The dissolution and in vitro release for F8 formulation.
study was shown that Eudragit RSPO, HPMC E50 LV in Ozcarbazepine sustained release matrix tablets
8:1 ratios more controlled the release of drug from were prepared successfully using combination of HPMC E
formulation. In case of tablets of F8, containing drug, 50LV & EUDRAGIT RSPO polymers and achieve required
Eudragit RSPO & HPMC E50LV in the ratio 1:8 the dissolution profile. The release pattern of optimized
release profile was showing 100 % of drug release in 24 formulation F8 was achieved the optimum USP limit when
hours, and also observed that release rate was matched with compared to marketed formulation. Drug release kinetics of
the USP results. It concludes F8 has better controlled this formulation corresponds best to Higuchi, Peppas and
release than the other formulations. The regression Korsemeyer model. The optimized formulation is
coefficients values for formulation F8 of zero order and controlled by a complex mechanism of diffusion and extent
first order Higuchi matrix, Peppas and Hixson-Crowell by erosion.
Table 1. Formulation design
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Ozcarbazepine 200 200 200 200 200 200 200 200 200 200
Eudragit RSPO 176 0 180 98 78 58 38 18 138 158
HPMC E50LV 0 176 58 78 98 118 138 158 38 18
Avicel 102 20 20 20 20 20 20 20 20 20 20
Mg state 4 4 4 4 4 4 4 4 4 4
Total 400 400 400 400 400 400 400 400 400 400
Table 2. Characterization of Trial Blends of all formulations
Bulk Density Tapped Compressibilty Hausner’s Angle Of
Formulation
(g/ml) Density (g/ml) Index (%) ratio(HR) Repose(ɵ)
F1 0.560 0.608 8 1.08 33
F2 0.608 0.700 13 1.15 32
F3 0.630 0.700 9.09 1.10 29
F4 0.583 0.700 16.66 1.20 28
F5 0.625 0.681 8.33 1.09 27
F6 0.652 0.750 13.04 1.15 32
F7 0.638 0.714 10.63 1.11 25
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Brahmaiah Bonthagarala. et al. / Singapore Journal of Pharmaceutical Research. 2014;1(1):1-7.
Stability studies
Table 6. Formulation F8 Stored at room temperature (25°c ± 2°c & 60% RH)
Drug Content Cum% Drug
Formulation Tested after days Hardness Kp Friability (%)
(%) Released
F8 15 6.8 0.08 99.92 100.65
F8 30 6.8 0.06 99.22 99.84
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Brahmaiah Bonthagarala. et al. / Singapore Journal of Pharmaceutical Research. 2014;1(1):1-7.
CONCLUSION
Ozcarbazepine sustained release matrix tablets (for tablet weight approx. 404 mg). The average percentage
were successfully formulated by using HPMC E 50LV & (%) drug content was also found within the USP limit and
EUDRAGIT RSPO polymers U.V. Scanning of shows the effectiveness of the mixing procedure. From the
Ozcarbazepine was performed and the λmax at 285.4 was in vitro studies, it was observed that with increasing the
found to be the most appropriate for the determination of concentration of Eudragit RSPO, the rate and extent of drug
concentration of unknown samples. Standard curve of release from the tablet decreases. This was due to the fact
Ozcarbazepine was prepared at λmax 285.4 nm and the that Eudragit RSPO is an insoluble polymer and showed
regression value was found to be 0.999. The tablets of low permeability. From in vitro studies, it was also
various formulations of Ozcarbazepine were prepared and observed that with increasing the concentration of HPMC
the tablet hardness was found to be in range of 6.5 to7.3 E50LV the rate and extent of drug release form the tablets
Kp. The average weight of the prepared tablets of various not much more effect. This is because HPMC E50LV is a
formulations was found to be within the USP limit i.e. ± 5% low viscosity polymer.
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