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Effect of Tablet Processing and Formulation Factors on Disintegration and

Dissolution of Aceclofenac Tablets

Article · February 2011

DOI: 10.37285/ijpsn.2010.3.4.9

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1240 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011
International Journal of Pharmaceutical Sciences and Nanotechnology

Volume 3 • Issue 4 • January – March 2011

Research Paper
Effect of Tablet Processing and Formulation Factors on Disintegration and
Dissolution of Aceclofenac Tablets

C Mallikarjuna Setty1, Muthadi Radhika1, V.R.M Gupta1, M.V.R. Reddy2, A.V. Jithan3
1
N.E.T. Pharmacy College, Raichur, India
2
St. Peters Institute of Pharmaceutical Sciences, Warangal, India
3
Mother Teresa College of Pharmacy, Hyderabad, India

ABSTRACT: Aceclofenac, a non-steroidal anti-inflammatory drug, is used for posttraumatic pain and rheumatoid
arthritis. The tablets were produced by simple wet granulation method. The post compressional parameters, hardness,
friability, drug content of all the formulations were within the official limits. The disintegration time did not change with the
type of diluents (mannitol, microcrystalline cellulose and dicalcium phosphate). However, it varied with the concentration of
polyvinylpyrrolidone and microcrystalline cellulose. As the concentration of acacia was decreased, disintegration time
decreased and hence, dissolution increased. Incorporation of superdisintegrants improved the disintegration time as well
as dissolution of the drug. As the granules size increased disintegration time decreased and increase in dissolution was
noticed. It can be concluded that the selection of combination of variables and levels were important in the optimization of
aceclofenac tablet formulation.

KEYWORDS: Aceclofenac; wet granulation; binders; diluents; superdisintegrants; dissolution; disintegration

Introduction various physiological functions associated with aging

including difficulty in swallowing, administration of intact
Aceclofenac, (2-[2-[2-(2,6-dichlorophenyl) aminophenyl]
tablet may lead to poor patient compliance and ineffective
acetyl]oxyacetic acid), a nonsteroidal antiinflammatory
therapy. The paediatric and geriatrics patients are of
drug (NSAID) has been indicated for various painful
particular concern. To overcome this, dispersible tablets
indications (Hinz et al., 2003) and proved as effective as (Schiermeier et al., 2002) and fast-disintegrating tablets
other NSAIDs with lower indications of gastro-intestinal (Mizumoto et al., 2005) have been developed. Most
adverse effects and thus, resulted in a greater compliance commonly used methods to prepare these tablets are;
with treatment (Legrand et al., 2004). Aceclofenac is freeze-drying/Lyophilization (Virley et al., 1990) tablet
practically insoluble in water. For poorly soluble orally molding (Dobetti et al., 2000) and direct-compression
administered drugs, the rate of absorption is often methods (Sunada et al. 1996). Lyophilized tablets show a
controlled by the rate of dissolution. Clear aceclofenac- very porous structure, which causes quick penetration of
loaded soft capsules have been prepared to accelerate the saliva into the pores when placed in oral cavity (Virley et
absorption (Yong et al., 2005). The rate of dissolution can al.,1990; Patrick et al., 1997). The main disadvantages of
be increased by increasing the surface area of available tablets produced are, in addition to the cost intensive
drug by various methods (micronization, complexation and production process, a lack of physical resistance in
solid dispersion) (Martin et al., 1993). The dissolution of a standard blister packs and their limited ability to
drug can also be influenced by disintegration time of the incorporate higher concentrations of active drug
tablets. Faster disintegration of tablets delivers a fine (Schiermeier et al., 2002). Moulded tablets dissolve
suspension of drug particles resulting in a higher surface completely and rapidly. However, lack of strength and
area and faster dissolution. taste masking are of great concern (Dobetti et al., 2000;
Of all the orally administered dosage forms, tablet is most Chang et al., 2000). Main advantages of wet granulation
preferred because of ease in administration, compactness are, low manufacturing cost and high mechanical integrity
and flexibility in manufacturing. Because of changes in of the tablets (Sunada et al., 1996; Takao et al ., 1996).

1240
 C. Mallikarjuna Setty et.al. : Effect of Tablet Processing and Formulation Factors on Disintegration and… 1241

Therefore, wet granulation appears to be a better option for Angle of repose

manufacturing of tablets. The tablets prepared by wet Angle of repose (α) was determined using funnel method.
granulation method, in general, are based on the action The blend was poured through a funnel that can be raised
established by binders, diluents, superdisintegrants such as vertically until a maximum cone height (h) was obtained.
croscarmellose sodium, crospovidone and sodium starch The radius of the heap (r) was measured and angle of
glycolate. The objective of the present work was to study repose was calculated.
the effect of functionality differences of superdisintegrants, α = tan–1 (h/r)
diluents, binders on the tablet properties disintegration and
dissolution of aceclofenac tablets. Compressibility index
The simplest way of measuring the of free flow property of
Materials and Methods a powder is compressibility, an indication of the ease with
Materials in this study were Aceclofenac, Primojel which a material can be induced to flow is given by %
(Sodium starch glycolate), Ac-Di-Sol (Croscarmellose compressibility which is calculated as follows:
sodium) and Polyplasdone XL 10 (Crospovidone), C = (ρt – ρb) / ρt × 100
Mannitol, Povidone K30 (Polyvinyl pyrrolidone), Starch,
Acacia, Micricrystalline cellulose, Dicalcium phosphate, ρt – Tapped density, ρb – Untapped bulk density
Magnesium stearate, Talc, Aerosil, Oil of peppermint.
Hausner’s ratio
Methods Hausner’s ratio is an index of ease of powder flow; it is
calculated by the formula:
Tablets containing 200 mg of aceclofenac were prepared by
wet granulation method and the various formulae used in the Hausner’s ratio = ρt\ ρb
study are shown in the table 1. The drug and diluent, (and ρt – Tapped density, ρb – Untapped bulk density
superdisintegrant) in required quantities and properly mixed
and granules were prepared by using with different binder Evaluation of tablets
solutions. The cohesive mass was passed through mesh All the tablets were evaluated for parameters such as
number 16 and dried at temperature of 450 C in hot air oven. hardness, friability, drug content, and In vitro dissolution
The dried mass was passed through mesh number 16/22 or study.
22/36. Then lubricants and glidants (Magnesium stearate,
and talc) were added mixed well and then compressed into Hardness (Ansel et al., 1995; Banker et al., 1987)
tablets. The tablets were prepared by wet granulation For each formulation, the hardness of tablets was
method using 8 mm biconcave punches on a ′Rimek Mini determined using the Fizer hardness tester (Cadmach,
Press 1’ a 10 station rotary compression mission. India).
Evaluation of Powder blends: (Martin et al., 1993; Fiese et Thickness
al., 1987; Ansel et al., 1995; Staniforth et al., 2007)
Thickness of tablet was determined by using dial caliper
Bulk density (Mitutoya, Model CD-6 CS, Japan).

Apparent bulk density (ρp) was determined by placing Friability test (Ansel et al., 1995; Banker et al., 1987)
presieved drug excipients blend into a graduated cylinder Twenty tablets were weighted and placed in the Roche
and measuring the volume (Vb) and weight (M) “as it it”. friabilator (Electolab, Mumbai) and apparatus was rotated
at 25 rpm for 4 min. After revolution, the tablets were
ρb = M/Vb dusted and weighed. The friability is given by the formula:
Tapped density F = (1 – Wo/W) x 100
The measuring cylinder containing a known mass of blend Where, Wo is the weight of the tablets before the test
was tapped for a fixed number of taps. The minimum and W is the weight of the tablet after the test.
volume (Vt) occupied in the cylinder and the weight (M) In weight variation test, twenty tablets were selected at
of the blend was measured. The tapped density (ρt) was random and average weight was determined using an
calculated using following formula. electronic balance (Shimadzu, AX200, Japan). Tablets
were weighed individually and compared with average
ρt = M/ Vt
weight.
 1242 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011

Table 1 Formulae used in the preparation of aceclofenac tablets.

Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 F13 F14 *F15 *F16 *F17 *F18 *F19 *F20

Aceclofenac 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100

Mannitol 78 78 78 78 78 - - 86 84 84 86 85 85 85 78 78 78 85 85 85

Polyvinylpyrrolidone 10 - - 10 10 4 2 - - 4 2 10 10 10 10 - - 10 10 10

Starch - 10 - - - - - - - - - - - - - - - - - -

Acacia - - 10 - - - - 2 4 - - - - - - - - - - -

Croscarmellose - - - - - - - - - - - - - 25 - - - - - -
sodium

Sodium starch - - - - - - - - - - - 25 - - - - - - - -
glycolate

Crospovidone - - - - - - - - - - - - 25 - - - - - - -

1242
Microcrystalline - - - 78 - 84 86 - - - - - - - - - - - - -
cellulose

Dicalcium - - - - 78 - - - - - - - - - - - - - - -
phosphate

Starch powder 4 4 4 4 4 4 4 4 4 4 4 - - - 4 4 4 - - -

Magnesium 4 4 4 4 4 4 4 4 4 4 4 1.25 1.25 1.25 4 4 4 1.25 1.25 1.25

stearate

Talc 4 4 4 4 4 4 4 4 4 4 4 - - - 4 4 4 - - -

Aerosil - - - - - - - - - - - 2.5 2.5 2.5 - - - 2.5 2.5 2.5

Oil of peppermint - - - - - - - - - - - 0.2 0.2 0.2 - - - 0.2 0.2 0.2

Tablet weight (mg) 200 200 200 200 200 200 200 200 200 200 200 250 250 250 200 200 200 250 250 250

*- granule size #22/36 (855µm)

 C. Mallikarjuna Setty et.al. : Effect of Tablet Processing and Formulation Factors on Disintegration and… 1243

Drug content thickness (4.15 to 4.3 mm) of tablets was not much
influenced by different binders. However, friability
Two tablets were powdered and the blend equivalent to
losses % varied with disintegrant type, the friability losses
200 mg of aceclofenac was weighed and dissolved in
% within the acceptable official limits indicated that tablets
suitable quantity of phosphate buffer of pH (7.4). The
had a good mechanical resistance. The content was found
solution was filtered, suitably diluted and the drug content
to be high (≥99.12%) in all the tablet formulations.
was analyzed spectroscopically at 274 nm. Each sample
was analyzed in triplicate (Indian Pharmacopoeia, 1996). The most important parameter that needs to be
optimized in the development of tablets is their
Disintegration and Dissolution Study disintegration time Table 3 shows disintegration values of
Disintegration time was determined using USP tablet the tablet formulations. In the present study, the F3
disintegration test apparatus (ED2L, Electrolab, India) formulation (with acacia as binder) the disintegration time
using 900 mL of distilled water without disk at room was significantly more (p>0.05) than for F1 and F2
temperature (30°C). The disintegration times of six formulations, and also did not pass the official limits. Of
individual tablets were recorded and the mean value was all the binders used, PVP shows the least disintegration
taken. time (3.5 min). From figure 1, it can be said that acacia
In vitro release of aceclofenac from tablets was exhibited more adhesive properties than
monitored by using 900 ml of SIF (USP phosphate buffer polyvinylpyrrolidone and starch paste and resulted in
solution, pH 5.8) at 37±0.5° and 75 rpm using higher disintegration time.
programmable dissolution tester [Paddle type, model TDT- In order to evaluate the efficiency of
08L, Electrolab, (USP), India]. Aliquots were withdrawn polyvinylpyrrolidone in the presence of other diluents, F4
at one minute time intervals and were replenished and F5 tablet formulations was prepared using
immediately with the same volume of fresh buffer microcrystalline cellulose and dicalcium phosphate
medium. Aliquots, following suitable dilutions, were respectively. The disintegration values were found to be
assayed spectrophotometrically (UV-1700, Shimadzu, 3.5 min and 4.5 min respectively for microcrystalline
Japan) at 274 nm. cellulose and dicalcium phosphate. From figure 2, it
indicates that disintegration times of the tablets was not
Result and Discussion influenced with the type of diluent used in the study and
were well within the acceptable official limits.
Although developing tablets offers a simple and effective
approach to formulate a new drug for oral administration, In order to study the effect of concentration of
it requires careful consideration of the physicochemical polyvinylpyrrolidone as binder in figure 3, two more
properties of the drug and the excipients. In addition, the formulations (F6 and F7) were prepared at two different
simple tablet must also undergo stringent regulatory concentration of polyvinylpyrrolidone using
restrictions. Hence, optimization of the formulation microcrystalline cellulose as diluent. Compared to F4,
variables is very important especially for poorly soluble there was no much change (between 3.5-4.5 min) in the
drugs. Since, the flow properties of the powder mixture disintegration of tablets with decreasing the concentration
are important for the uniformity of mass of the tablets, the of polyvinylpyrrolidone (to 1 or 2 % w/w) in the tablets.
flow of the powder mixture was analyzed before Figure 3, indicates that at any concentration studied,
compression to tablets. Table 2 shows precompressional polyvinylpyrrolidone can produce tablets having
parameters of powder mixture. Angle of repose (≤ 28.72), disintegration time well within the acceptable
Compressibility index (≤12.37), low Hasner`s ratio (≤1.16) pharmacopoeial limts.
values indicated a fairly good flowability of powder
mixture. As the tablet powder mixture was free flowing, With an intention to study the effect of concentration of
tablets produced were of uniform weight with acceptable acacia as binder, the concentration of acacia was lowered
weight variation (≤ 4.68%) due to uniform die fill. In the in formulations F8 and F9. Disintegration time decreased
tablet formulation F1, F2, F3, three different binders (PVP, from 17.5 min (F3) to 3min and 4.5 min in F8 and F9
Starch and Acacia respectively) at 5 % level was used to formulations respectively. From figure 4, indicates that
evaluate the efficiency of binders with respect to post acacia can produce tablets having acceptable
compressional parameters. Hardness (4.1-4.4 kg/cm2) and disintegration time at lower concentration (2-1% w/w).
1244 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011

Table 2 Aceclofenac Precompressional Blend Characterization.

Formulations Angle of Repose (θ) Compressibility (%) Hausner’ ratio

(±SD), n=3 (±SD), n=3 (±SD), n=3
F1 24.46 (0.24) 4.45 (0.12) 1.04 (0.01)
F2 27.08 (0.29) 0.69 (0.56) 1.09 (0.01)
F3 28.72 (0.29) 7.95 (1.61) 1.07 (0.06)
F4 27.96 (0.45) 5.33 (0.09) 1.05 (0.01)
F5 25.69 (0.01) 6.51 (0.74) 1.06 (0.01)
F6 24.97 (0.22) 10.85 (1.20) 1.10 (0.01)
F7 22.94 (0.59) 12.37 (0.41) 1.10 (0.02)
F8 24.94 (0.22) 12.25 (1.20) 1.15 (0.01)
F9 24.94 (0.59) 12.37 (0.86) 1.16 (0.02)
F10 24.27 (0.14) 7.75 (0.35) 1.10 (0.05)
F11 26.07 (0.10) 10.87 (1.20) 1.04 (0.04)
F12 24.27 (0.25) 5.09 (0.49) 1.04 (0.04)
F13 25.45 (0.12) 8.05 (0.27) 1.04 (0.08)
F14 25.45 (0.01) 6.85 (8.39) 1.04 (0.08)
F15 26.35 (0.02) 11.05 (0.27) 1.13 (0.08)
F16 26.35 (0.01) 7.08 (8.39) 1.15 (0.08)
F17 26.63 (0.49) 10.4 (0.84) 1.15 (0.05)
F18 24.86 (0.53) 7.75 (0.35) 1.01 (0.01)
F19 25.35 (0.49) 6.10 (0.56) 1.02 (0.04)
F20 25.77 (0.48) 6.50 (0.42) 1.04 (0.04)

Table 3 Aceclofenac Precompressional tablet Characterization

Hardness test Friability (%) Thickness Disintegration Time

Formulations 2
(Kg/cm ) (SD±), n=6 (SD±), n=10 (mm) (SD±), n=6 (min) (SD±), n=6
F1 4.1 (0.1) 0.162 (0.01) 4.15 (0.05) 3.5 (0.5)
F2 4.1 (0.1) 0.417 (0.04) 4.25 (0.05) 4.5 (0.5)
F3 4.1 (0.1) 0.329 (0.05) 4.35 (0.05) 17.5 (0.5)
F4 4.3 (0.1) 0.277 (0.005) 4.15 (0.15) 3.5 (0.5)
F5 4.1 (0.1) 0.331 (0.003) 4.25 (0.05) 4.5 (0.5)
F6 4.1 (0.1) 0.368 (0.003) 4.45 (0.05) 4.5 (0.5)
F7 4.1 (0.1) 0.235 (0.01) 4.15 (0.15) 3.5 (0.5)
F8 4.1 (0.1) 0.208 (0.006) 4.55 (0.05) 3.0 (1)
F9 4.1 (0.1) 0.260 (0.07) 4.15 (0.15) 4.5 (0.5)
F10 4.1 (0.1) 0.277(0.005) 4.23 (0.05) 7.0 (0.5)

Table 3 contd…
 C. Mallikarjuna Setty et.al. : Effect of Tablet Processing and Formulation Factors on Disintegration and… 1245

Hardness test Friability (%) Thickness Disintegration Time

Formulations 2
(Kg/cm ) (SD±), n=6 (SD±), n=10 (mm) (SD±), n=6 (min) (SD±), n=6
F11 4.2 (0.1) 0.210 (0.05) 4.15 (0.05) 9.0 (0.5)
F12 4.4 (0.1) 0.256 (0.005) 4.95 (0.05) 0.24 (0.25)
F13 4.3 (0.1) 0.210 (0.002) 4.25 (0.05) 0.19 (0.5)
F14 4.3 (0.1) 0.160 (0.02) 4.15 (0.05) 0.27 (0.5)
F15 4.1 (0.1) 0.258 (0.01) 4.75 (0.25) 10.15 (0.75)
F16 4.35 (0.1) 0.231 (0.01) 4.15 (0.05) 14.0 (1)
F17 4.1 (0.1) 0.289 (0.009) 4.95 (0.05) 15.0 (1)
F18 4.1(0.05) 0.285 (0.001) 4.75 (0.95) 0.54 (2.5)
F19 4.1 (0.1) 0.312 (0.09) 4.95 (0.05) 0.45 (2.5)
F20 4.25 (0.05) 0.257 (0.05) 4.75 (0.25) 0.57 (2.5)

120
% drug release

100
80
60
40
20
0
0 20 40 Time 80
60 (min) 100

Fig. 1 Effect of binders on the release of aceclofena

Key: (♦) – F1 (Polyvinylpyrrolidine); –F2(Starch paste); (▲) –F3 (Acacia)

120
100
80
% drug release

60
40
20
0
0 50 100 150 200 250 300 350
Time (min)

Fig. 2 Effect of diluents on the release of aceclofenac.

Key: (♦) – F1 (Mannitol); –F4 (Microcrystalline cellulose); (▲) –F5 (Dicalcium phosphate)
1246 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011

120
100
80

% drug release
60
40
20
0
0 50 100
Time (min)
150 200

Fig. 3 Effect of concentration of polyvinylpyrrolidone (microcrystalline cellulose) on the release profile.

Key: (♦)-F4 (pvp-5%); (∆)-F6 (pvp-2%); (▲)-F-7 (pvp-1%)

120

100

80
% drug release

60

40

20

0
0 20 40 60
Time (min) 80 100

Fig. 4 Effect of concentration of acacia on drug release.

Key: (♦)-F3 (Acacia-5%) ; (□)-F8 (Acacia-2%); (▲)-F9 (Acacia-1%)

To study the effect of concentration of superdisintegrants in the tablets. The marked improvement
polyvinylpyrrolidone (5-1%) in presence of mannitol as in the tablet disintegration may be attributed to
diluent, F10 and F11 tablets were prepared. As the superdisintegrant that rapidly uptake of water, swell and
concentration of polyvinylpyrrolidone decreased, the exert sufficient pressure inside tablet to break apart into
disintegration time increased from 3.5 to 9 minutes is small segment (Sunada et al., 2002).
shown in figure 5.
Effect of granule size on the disintegration
In order to study the effect of superdisintegrants (such
as, croscarmellose sodium, crospovidone and sodium Tablets were also compressed using initial granule size of
starch glycolate)is shown in (figure 6), on the 567 μm (#22/36). F15, F16 and F17 tablet formulations
disintegration of tablets, F12, F13 and F14 tablets were having formulae similar to F1, F2 and F3 were prepared by
prepared. Table 3 shows that disintegration time decreased compressing the granules (#22/36) with mean size of 567
significantly compared to those tablets (F1) without μm, instead of 855 μm (#16/22), (figure 7).
superdisintegrants. This may be due to the presence of Disintegration time changed from 3.5 to 15 min, 4.5 to 14
 C. Mallikarjuna Setty et.al. : Effect of Tablet Processing and Formulation Factors on Disintegration and… 1247

min, and 17.5 to 15 min. These results indicate that Comparison of t50% and t80% values of F4, F5 and F7
disintegration time increases (except with acacia binder) indicates that there was no much change in the t50% value,
with decreasing the initial granule size. Similarly, F18, however, t80% values decreased (71.5 to 40.25 min). The
F19, and F20 tablet formulations containing different decrease in the t80% values may be due to the more of
superdisintegrants (croscarmellose sodium, crospovidon, disintegrating effect of microcrystalline cellulose in the
and sodium starch glycolate) were also prepared using
latter times in F6 and F7 than combined binder and
initial granule (#22/36) size of 567μm. Table 3 shows that
disintegrant effect in F4 that delayed the formation of fine
disintegration time increased from 0.24 min to 0.54 min,
0.19 min to 0.45 min and 0.27 min to 0.57 min, particles and hence dissolution.
respectively with F18, F19 and F20. These results also In the tablets F3, F8 and F9, the concentration of the
demonstrated that increasing initial granule size decreases binder, acacia, was varied (5-1%) As the concentration of
the disintegration time significantly. The tendency that acacia was dropped to 1% (F9), the t50% and t80% values
porosity of tablets compressed from granules with bigger decreased. However, there was no much difference in the
particle size (855μm) might have higher porosity than
t50% and t80% values of F3 and F8 tablets, indicates that 1%
those compressed from of granulations having smaller
acacia is optimum as binder level of tablets.
particles (567μm), as the smaller particles are easily
shifted against each other in contrast to those fixed more As the concentration of polyvinylpyrrolidone decreased
apart in bigger granules. Similar results can be correlated from 5-1% (F1, F10 and F11) the t50% and t80% values
with the results of Schreiner et al (2005) found with increased from 8.8 min to 15.5 min, it indicates that
powder blend and granules of the same composition. polyvinylpyrrolidone acts as water-soluble carrier. The
increasing the dissolution rate with decreasing the
In vitro release studies
concentration of polyvinylpyrrolidone is probably due to a
Dissolution profiles of aceclofenac from tablets prepared decrease in the disintegration time and wettability
with three different types of binders (polyvinylpyrrolidone, improvement and local solubilization effect of carrier at
starch paste and acacia) are shown in figure-1. The tablets the diffusion.
were prepared using a binder concentration of 5% w/w.
In the next part of this work, superdisintegtrants (10%)
t50% and t80% values (table-4) were dependent on the type of
were used to influence the tablet performance.
disintegrant and were in the following order F1<F2<F3.
Formulations (F12, F13 and F14) were prepared using
The lower values with polyvinylpyrrolidone tablets may be
sodium starch glycolate (F12), crospovidone (F13),
attributed to the high hydrophilic property, and
croscarmellose sodium (F14). Compared to formulation
polyvinylpyrrolidone might have behaved as water soluble
without superdisintegrant (i.e., F1), the t50% and t80% values
carrier in the tablets. While, starch and acacia were
decreased significantly (p<0.05) with tablets containing
although hydrophilic, might have imparted more adhesive
superdisintegrants. The increasing in the dissolution of
properties as well and acacia may increase this effect. The
drug with superdisintegrants may be attributed to the rapid
interdependence between the functionality of binders used,
disintegration of (table-4), tablets into smaller particles.
thus determines the dissolution.
Thus increase in the surface area due to the decreased
Tablets were also prepared with three different diluents particle size in the dissolution medium leads to the rapid
(microcrystalline cellulose, dicalcium phosphate, dissolution and hence smaller t50% and t80% values.
mannitol). The dissolution profiles of these tablets (F1, F4,
and F5) are shown in figure-2. Comparison of t50% and t80% Effect of granule size on the dissolution
values (table-4) indicates that the dissolution of drug was F15, F16 and F17 tablets were prepared using granules
faster with mannitol tablets (F1) than other (F4 and F5). size of 567μm (#22/36) is shown in (fig.8). The t50% and
The faster dissolution with F1 tablets may be due to the t80% values increased significantly (p ≤ 0.05) as the initial
hydrophilic diluent inside the tablet. granules size decreased from 855μm to 567μm. Following
In order to study the effect of concentration of the explanation of Schreiner et al (2005) for higher
polyvinylpyrrolidone as binder two more formulations (F6 porosities of tablets compressed from powder mixture than
and F7) were prepared at two different concentrations (2- those pure powder with the same composition.
1%) using microcrystalline cellulose as diluent. Accordingly, in this study, higher porosities of tablets
1248 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011

prepared from bigger granule (#16/22) 855μm, might have Comparison of the tablets with same composition having
allowed the rapid absorption of water inside the tablets with granule size of 855μm (# 16/22) i.e., F12, F13 and
causing the rapid disintegration followed by rapid F14, the t50% and t80% values increased significantly due to a
dissolution. Figure-8 shows the effect of superdisintegrants decrease in the initial granules size that might have made
on the release of aceclofenac from tablets prepared by the tablets having smaller porosities.
using granules having the size of 567μm (#22/36).

120

100

80
% drug release

60

40

20

0
Time (min)
0 20 40 60 80 100

Fig. 5 Effect of concentration of polyvinylpyrrolidone (mannitol as diluent on the release profile.

Key: (♦)-F1 (pvp-5%); (■) -F10 (pvp-2%); (▲)-F-11 (pvp-1%)

120

100

80
% drug release

60

40

20

0
0 10 20 30 40
Tim e (m in)

Fig. 6 Effect of superdisintegrants on the release of aceclofenac

Key: (♦)-F; (■) -F12 (Sodium starch glycolate) ;(▲)-F13 (Crospovidone) ; (Δ)-F-14 (Croscarmellose sodium).
 C. Mallikarjuna Setty et.al. : Effect of Tablet Processing and Formulation Factors on Disintegration and… 1249

120

100
% drug release
80

60

40

20

0
0 50 100 150
Time (min)

Fig. 7 Effect of particle size on the release of aceclofenac.

Key: (♦)-F1; (■)-F2; (▲)-F3; ◊-F15 ; (□)-F16 ; (∆) – F17

Table 4 Dissolution parameters (t50% and t80% ), drug content.

Formulations T50% (min) (± SD), n=3 t 80% (min) (± SD), n=3 Drug content (%) (± SD), n=3
F1 8.83 (0.55) 12.3 (0.17) 99.72 (0.27)
F2 15.03 (0.57) 35.36 (0.75) 99.74 (0.26)
F3 41.66 (0.57) 71.5 (1.32) 99.22 (0.22)
F4 19.66 (0.57) 73.33 (1.72) 99.56 (0.10)
F5 22.66 (1.52) 55.66 (1.15) 99.44 (0.44)
F6 20.23 (0.25) 40.25 (0.25) 99.44 (0.44)
F7 20.25 (0.35) 40.25 (0.35) 99.25 (0.22)
F8 7.66 (0.57) 12.16 (0.28) 99.61 (0.16)
F9 6.96 (0.05) 12.33 (0.28) 99.73 (0.73)
F10 15.05 (0.57) 51.0 (2.21) 99.89 (0.37)
F11 13.0 (1.41) 32.5 (0.70) 99.47 (0.47)
F12 6.75 (1.06) 11.5 (0.70) 99.12 (0.12)
F13 4.5 (0.70) 7.5 (0.70) 99.47 (0.025)
F14 1.25 (0.07) 16.5 (0.70) 99.33 (0.47)
F15 10.5 (0.70) 29.3 (0.70) 99.89 (0.37)
F16 12.25 (0.35) 60.25 (0.35) 99.65 (0.22)
F17 30.25 (0.35) 72.25 (0.70) 99.22 (0.22)
F18 18.25 (0.35) 25.5 (0.70) 99.47 (0.47)
F19 12.25 (0.35) 18.25 (0.35) 99.33 (0.33)
F20 9.75 (0.35) 16.5 (0.75) 99.61 (0.33)
1250 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 4 • January-March 2011

120

100

80
% drug release

60

40

20

0
0 10 20 30
Time (min)

Fig. 8 Effect of particle size of superdisintegrants on the release of aceclofenac.

Key: (♦) -F12 ; (■)-F13 ; (▲)-F14; ◊-F18 ; (□)-F19 ; (∆) – F20

Conclusion Chang RK, Guo X, Burnside B, Couch R. Fast-dissolving tablets.

It is concluded that the formulation variables such as, Pharm .Techno. 24: 52-8 (2000).
diluents (mannitol, microcrystalline cellulose and Dobetti L. Fast-melting tablets: Developments and technologies.
dicalcium phosphate), binders (polyvinylpyrrolidone, Pharm .Technol .Eur. 12:32-42 (2000).
starch paste and acacia), superdisintegrants (sodium starch
glycolate, crospovidone and croscarmellose sodium) and Fiese EF, Hagen TA. Preformulation. In: Lachman L, Lieberma
initial granule size influenced the performance of tablet. HA, Kanig JL. The theory and practice of industrial
Therefore, selection of combination of variables and levels pharmacy. 3rd ed. Mumbai, pp. 182 184.
are crucial in the optimization of an aceclofenac tablet
Hinz B, Auge D, Rau T, Rietbrock S, Brune K, Werner U.
formulation.
Simultaneous determination of aceclofenac and three of its
metabolites in human plasma by high-performance liquid
Acknowledgement chromatography. Biomed. Chromatogr. 17: 268-75 (2003).
Authors wish to acknowledge Maple Biotech Pvt Ltd, Ho T, Hersey JA. Compactability of granules prepared by a novel
Pune, India for providing croscarmellose sodium, sodium method of granulation and their dissolution. J. Pharm.
starch glycolate and microcrystalline cellulose as gift Pharmacol. 32: 160-6 (1980).
samples. Authors are grateful to Aristo Pharmaceuticals
Indian Pharmacopoeia. (Vol. 2), New Delhi, 1996, pp.555 6.
Ltd, Mumbai, India and Ranbaxy, New Delhi, India for
providing aceclofenac as gift samples. Kornasoff D, Frerick H, Bowdler J, Montull E. Aceclofenac is a
well-tolerated alternative to naproxen in the treatment of
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