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Original Article
EFFECT OF ADDITIVES ON IN-VITRO RELEASE OF ORODISPERSIBLE DOSAGE FORM
MAMDOUH M. GHORAB
1
, MOHAMED M. ELSAYED
2
, ALI M. NASR
2
, SHADEED GAD
1,2
1
Department of pharmaceutics, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt,
2
Department of Pharmaceutics, Faculty of
Pharmacy and Pharmaceutical Industries, Sinai University, El-Arish, North Sinai, Egypt.
Email: mghorab@hotmail.com
Received: 22 Nov 2014 Revised and Accepted: 15 Dec 2014
ABSTRACT
Objective: The aim of this investigation was to prepare orodispersible tablets of meloxicam using various concentrations of superdisintegrants like
Ac-DI-Sol, crospovidone, sodium starch glycolate by the direct compression method.
Methods: Nine formulae of Meloxicam orodispersible tablets were prepared. These tablets were evaluated for their drug content, weight variation,
friability, hardness, wetting time, In-vitro disintegration time and drug release.
Results: All the formulation exhibited hardness between 4.21–4.55 kg/cm
2
. The tablets were disintegrating within 8.3 to 21.9 sec. Dissolution
studies revealed that formula containing 7.5 % sodium starch glycolate showed 100% of drug release, at the end of six minutes. Among the
formulated tablets, formula F9 containing 7.5 % sodium starch glycolate showed superior organoleptic properties along with excellent In-vitro
disintegration time and drug release as compared to other formulae. The concentration of superdisintegrants had an effect on disintegration time
and In-vitro drug dissolution whereas hardness and friability of resulting tablets were found to be independent of disintegrant concentration. It was
concluded that the superdisintegrants addition technique is a useful method for preparing orodispersible tablets by the direct compression method.
Keywords: Meloxicam, Orodispersible tablets, Ac-Di-Sol, Crospovidone, Sodium starch glycolate, Superdisintegrant, Direct Compression, In-vitro.
INTRODUCTION
Oral route of drug administration have wide acceptance up to 50-
60% of total dosage forms. Solid dosage forms are popular because
of ease of administration, accurate dosage, self-medication, pain
avoidance and most importantly the patient compliance [1]. The
most popular solid dosage forms are being tablets and capsules; one
important drawback of this dosage form for some patients, is the
difficulty to swallow [2].
A constant focus on Novel Drug Delivery systems that offer greater
patient compliance, effective dosages and minimal chances of side
effects has led to the development of orodispersible tablets [3].
Mouth dissolving tablets are gaining more demand and popularity
from the last few years because Pharmaceutical industry has become
increasingly aware of the need that the elderly be considered as a
separate and unique Medicare population. Though geriatric patients
constitute a minor proportion of the population, its growth rate is
high and hence will have significant impact on the development of
drug delivery system [4]. Orodispersible tablets (ODTs) are not only
indicated for people who have swallowing difficulties, but also are
ideal for active people [5].
Orodispersible tablets are also called as mouth dissolving tablets,
melt-in the mouth tablets, fast dissolving tablets, rapimelts, porous
tablets, quick dissolving etc. Orodispersible tablets are those when
put on tongue disintegrate instantaneously releasing the drug which
dissolve or disperses in the saliva [6]. The faster the drug into
solution, quicker the absorption and onset of clinical effect. Some
drugs are absorbed from the mouth, pharynx and esophagus as the
saliva passes down into the stomach [7].
The advantage of mouth dissolving dosage forms is increasingly being
recognized in both, industry and academics [8]. Their growing
importance was underlined recently when European pharmacopoeia
adopted the term “Orodispersible tablet, ” as a tablet that to be placed
in the mouth where it disperses rapidly before swallowing [9].
According to European pharmacopoeia, the ODT should
disperse/disintegrate in less than three minutes. The basic approach
in the development of MDT is the use of superdisintegrants like
cross linked carboxymethyl cellulose (croscarmellose), sodium
starch glycolate (primogel, explotab), polyvinylpyrollidone
(polyplasdone) etc., which provide instantaneous disintegration of
the tablet after putting on the tongue, their by release the drug in
saliva [10]. The bioavailability of some drugs may be increased due
to absorption of drug in oral cavity and also due to pregastric
absorption of saliva containing dispersed drugs that pass down into
the stomach. More ever, the amount of drug that is subject to first
pass metabolism is reduced as compared to standard tablet [11].
Meloxicam is a nonsteroidal anti-inflammatory drug of the oxicam
class, used to relieve the symptoms of arthritis, primary
dysmenorrhea, fever, and as an analgesic, especially where there is
an inflammatory component [12]. Meloxicam inhibits
cyclooxygenase (COX) synthesis. This enzyme is responsible for
converting arachidonic acid into prostaglandin H
2
. This is the first
step in the synthesis of prostaglandins, which are mediators of
inflammation. Meloxicam has been shown, especially at its low
therapeutic dose, selectively to inhibit COX-2 over COX-1 [13]. A
primary advantage of the oxicam family of drugs is their long half-
life which permits once-day dosing [14]. In gastric disease, lower
dose of meloxicam is required 7.5 mg/day. Meloxicam is safer than
other NSAID’s [15]. Hence, in the present study an attempt was
made for preparation of fast disintegrating tablets of meloxicam
with the aim of providing faster onset of action.
MATERIALS AND METHODS
Meloxicam was received as a gift sample from Medical Union
Pharmaceuticals (MUP). Ac-Di-Sol, Crospovidone and Sodium starch
glycolate were obtained as gift samples from Egyptian International
Pharmaceutical Industries Company (EIPICO). Aspartame and
Microcrystalline cellulose kindly donated by Amoun pharmaceutical
Company. Mannitol, Magnesium stearate and Talc were of analytical
grade and were used as received. Methanol, PureLab, Madison,
(USA). Sodium hydroxide, OxfordLab, Mumbai, (India). Sodium
dihydrogen phosphate, PureLab, Madison, (USA).
Methodology
Selection of tableting method
For selecting the tableting method, compressible characteristics of
the drug are to be considered. For drugs, which are poorly
compressible and have moderate to high dose the most obvious and
International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491 Vol 7, Issue 2, 2015
Innovare
Academic Sciences
Ghorab et al.
Int J Pharm Pharm Sci, Vol 7, Issue 2, 283-289
284
direct attack would be to follow wet granulation method. For drugs
with low to moderate doses, direct compression technique offers
various advantages to the pharmaceutical formulation in terms of: -
Economy, because the less number of processing steps, persons and
time is required; - Stability, because a product is not required to
expose to a moisture and heat; - Performance, since tablets will
directly disintegrate gives higher dissolution. In the present work,
the direct compression technique was used to prepare
Orodispersible Meloxicam tablets.
Choice of tablet excipients
Excipients are critical to the design of any drug delivery system and
play a major role in determining its quality and performance. The
following excipients were selected for the formulation of
Orodispersible meloxicam tablets. Diluents: a combination of
Mannitol and microcrystalline cellulose (Avicel PH102);
Disintegrants: Ac-Di-Sol (croscarmellose sodium), polyplasdone-XL
(crospovidone), Primogel (sodium starch glycolate); Binders:
microcrystalline cellulose (Avicel PH 102); Sweetener: Aspartame;
Lubricants/Glidants: magnesium stearate and talc.
Micromeritic properties of mixed blend of meloxicam and
excipients
All the elements were passed through sieve number 60. Required
quantity of each ingredient was taken for each specified formulation
and all the ingredients were co-ground in a mortar and pestle. The
powder blend was evaluated for the following flow tests:
Angle of repose
Angle of repose was determined using the funnel method. The blend
was poured through a funnel that can be raised vertically at a fixed
height (h) in all experiments. The radius of the heap (r) was
measured and the angle of repose (θ) was calculated using the
following equation:
Angle of repose, Tan (θ) = h / r; Where θ = Angle of repose, h =
Height of the heap, are = Radius of pile [16].
Bulk and tapped densities
Apparent bulk density (D
b
) was determined by pouring the blend
into a graduated cylinder. The bulk volume (V
b
) and weight of the
powder (M) was determined [17].
D
b
= M / V
b
;
where M = Weight of powder, V
b
= Bulk volume
The measuring cylinder containing a known mass of the blend was
tapped for a fixed time. The minimum volume (V
t
) occupied in the
cylinder and the weight (M) of the blend was measured to calculate
the apparent tapped density [17].
D
t
= M / V
t
;
where M = Weight of powder, V
t
= Volume after tapping
(tapped volume)
Carr’s index (compressibility %)
The simplest way of measurement of free flow of powder is
compressibility. This percent is indirectly related to the relative flow
rate, cohesiveness, and particle size of a powder. The compressibility
percent of a material can be estimated as [18]
.
Compressibility % = [(D
t
– D
b
) / D
t
] x 100
Hausner ratio
Hausner ratio is an indirect index of ease of powder flow [19]. It is
the ratio between bulk density and tapped density
Hausner ratio = D
t
/ D
b
;
where D
t
= Tapped density, D
b
= Bulk density
Preparation of orodispersible tablets
Meloxicam orodispersible tablets were prepared by direct
compression method according to the formulae given in the table
(1). A total number of nine formulations were prepared. All the
ingredients were passed through 60-mesh sieve separately and
collected. The drug and microcrystalline cellulose were mixed in a
small portion of both at each time and blended to get a uniform
mixture and kept aside. Then the remaining ingredients were
weighed and mixed in geometrical order and the tablets were
compressed using flat face 8 mm size punch to get a tablet of 200 mg
weight using 10 stations rotary tabletting compression machine.
Evaluation of the formulated meloxicam ODTs
Weight variation
Twenty tablets from each formulation were selected randomly and
average weight was determined. Then individual tablets were
weighed and was compared with average weight [20].
Thickness and diameter
The thickness and diameter of the tablets were measured using
vernier caliber. It is expressed in mm [20].
Hardness
Hardness or tablet crushing strength (Fc), the force required to
break a tablet in a diametric compression, was measured using
Campbell tablet hardness tester[21]. It is expressed in kg/cm
2
.
Friability test
Friability of tablets was determined using Roche Friabilator. This device
subjects the tablets to the combined effect of abrasion and shock in a
plastic chamber revolving at 25 rpm and dropping the tablets at a height
of 6 inches at each revolution. Preweighed sample of tablets was placed
in a friabilator and the tablets were subjected to 100 revolutions. Tablets
were then dusted using a soft muslin cloth and reweighed[22].
The friability (F) is given by the following formula:
F = Winitial - Wfinal / Winitial x 100
In vitro disintegration time
Tablets were added to 10 ml of phosphate buffer solution of pH 7.4
at 37 ± 0.5˚C. The time required for the disintegration of the tablets
was noted[23].
Wetting time
The wetting time of the tablets was measured using a simple
procedure. Five circular tissue papers were placed in a Petri dish
which covered the entire surface area of the Petri dish. Phosphate
buffer solution pH 7.4 (10 ml) at 37 ± 0.5˚C was added to the Petri
dish. A tablet was carefully placed on the surface of tissue paper. The
time required for water to reach the upper surface of the tablets was
noted as the wetting time[24].
Water absorption ratio
The weight of the tablet prior to placement in the Petri dish was
noted (wb). The wetted tablet was removed and reweighed (wa).
The water absorption ratio was then determined according to the
following equation [25]
.
R= 100 x (w
a
-w
b
) /w
b
, Where w
b
and w
a
were tablet weights before
and after water absorption, respectively.
Drug content
Twenty tablets were weighed and powdered. An amount of the
powder equivalent to 30 mg of Meloxicam was transferred to a
clean, dry, calibrated 100 ml volumetric flask, dissolved in 10 ml of
1M NaOH and 40 ml methanol and mix well for 5 minutes. Further
40 ml methanol was added and mixed for 3 hours using a magnetic
stirrer. The flask was cooled and sufficient methanol was added to
produce 100 ml and filter to produce stock solution (300 mcg/ml).
Five mls of the stock solution was transferred to clean, dry,
calibrated 100 ml volumetric flask and the volume was made up
with methanol. The concentration of this solution was (15 mcg/ml).
This solution was analyzed for drug content at 364 nm using UV-
Visible spectrophotometer[26].
In-vitro dissolution study
In-vitro drug release studies of all the formulations were carried out
using USP dissolution test apparatus Type 2 (paddle) at 50 rpm.
Ghorab et al.
Int J Pharm Pharm Sci, Vol 7, Issue 2, 283-289
285
Phosphate buffer pH 7.4 was used as the dissolution medium with
temperature maintained at 37±0.5ºC. Five ml aliquot was withdrawn
at the specified time interval, filtered through whatmann filter
paper, and assayed spectrophotometrically at 362 NM using UV-
Visible spectrophotometer. An equal volume of fresh medium, which
was pre warmed at 37°C was replaced in the dissolution medium
after each sampling to maintain the constant volume throughout the
test. The study was performed in triplicate[27].
RESULTS AND DISCUSSION
Selection of tableting method
In the present study, the direct compression technique was
employed to prepare Orodispersible tablets of Meloxicam. Direct
compression technique offers various advantages to the
pharmaceutical formulation in terms of the economy, because the
less number of processing steps, persons and time are required;
stability, because a product is not required to expose to a moisture
and heat; performance, since tablets will directly disintegrate gives
higher dissolution.
Selection of tablet excipients
Excipients are critical to the design of any drug delivery system and
play a major role in determining its quality and performance. The
following excipients were selected for the formulation of
Orodispersible tablets of Meloxicam.
Diluents
Tablet prepared using the insoluble nature of crystalline cellulose
were found to have a gritty mouth feel. To overcome this problem
we attempted the use of water-soluble diluents Mannitol. But the
tablet prepared with Mannitol took long time to disintegrate
probably for the fact that tablets prepared with Mannitol often tends
to dissolve rather than disintegrate[28]. Thus, novel diluents, a
combination of Mannitol and microcrystalline cellulose (Avicel PH
102) were employed in this study.
Disintegrants
Short disintegration time with good dispersibility is the most
important characteristics of an orally disintegrating or mouth
dissolving tablets. The necessity of an orally disintegrating tablet is
to disintegrate within seconds, in a limited amount of the water
available in the form of saliva. This demands the use of special type
of disintegrants called as “Superdisintegrants” [29]. In the present
study, Ac-Di-Sol (croscarmellose sodium), polyplasdone-XL
(crospovidone), Primogel (sodium starch glycolate) were used as
superdisintegrants.
Binders
In the present study the microcrystalline cellulose (Avicel PH 102) is
as effective as a binder in direct compression.
Sweetener
Aspartame is used as an intense sweetening agent in pharmaceutical
preparation, including tablets, powder mixers and vitamin
preparation. Its appropriate sweetening power is 180-200 times
that of sucrose. It does not posses bitter after taste.
Lubricants/Glidants
Lubricants are intended to reduce the friction during compression,
and ejection of tablets. In the present study, magnesium stearate and
talc were used.
Micromeritic properties of mixed blend of Meloxicam and
excipients
Direct method for calculating the flowability
Angle of repose (θ)
The angle of repose has been used in several branches of sciences to
characterize the flow properties of solids. Angle of repose is a
characteristic related to interparticulate friction or resistance to
movement between particles. Angle of repose results is reported to
be very dependent upon the method used. Experimental difficulties
arise as a result of segregation of material and consolidation or
aeration of a powder as the cone is formed. Despite its difficulties,
the method continues to be used in the pharmaceutical industry, and
a number of examples demonstrating its value in predicting
manufacture problems appear in the literature.
The angle of repose is the constant, three dimensional angle (relative
to the horizontal base) assumed by a cone-like pile of material
formed by any of several different methods [30].
The two most important attributes for the direct compression
formula are good flow and good compressibility. The values
obtained for bulk density and tapped density does not affect the
compression of tablets. The angle of repose gives important
information about the flow characteristics of the powder mixture.
The powder flow depends on three general areas: the physical
properties of the particle (e. g., shape, size, compressibility), the bulk
powder properties (e. g., size distribution, compaction); and the
processing environment (e. g., storage, humidity) [31].
The angle of repose was found to affect the flowability of the
particles or granules. The values less than 20° exhibit excellent
flowability; the values between 20 and 30° show good flowability;
the values between 30 and 34° exhibit passable flowability; while
the values above 34° show very poor flowability [32]. USP
specificationsfor the values of the angle of repose were different
from the previous publication and these values are: 25-30
o
indicates
excellent flow, 31-35° indicates a good flow, 36-40° the flowability of
a powder is fair, 41-45° passable flowability, 46-55° poor, and > 55°
indicates very poor flow properties for a powder.
The values obtained for the angle of repose of the Meloxicam
powder blend ranged from 31.96° to 38.75°, as shown in table (2).
These values indicate that all formulae have good to fair flowability.
Good flowability was shown in four formulae, while five formulae
had a fair flowability. Thus, it is concluded that the blend of powder
was free flowing and can be used for direct compression.
The rank order for the calculated values of the Angel of repose was
arranged in descending order as follows: F9 (7.5 % sodium starch
glycolate), F8 (5 % sodium starch glycolate), F4 (2.5 %
crospovidone), F1 (2.5 % croscarmellose sodium), F2 (5 %
croscarmellose sodium), F7 (2.5 % sodium starch glycolate), F5 (5 %
crospovidone), F6 (7.5 % crospovidone, F3 (7.5 % croscarmellose
sodium).
Indirect methods for calculating the flowability
a- The bulk and tapped densities
The flow properties of the prepared Meloxicam powder blend were
investigated by measuring both the bulk density and the tapped
density. From theses values both the Hausner ratio and the Carr’s
index can be derived [33]. Both the bulk and tapped densities were
determined by equations described before, as illustrated in table (2).
These two parameters are related to the flow properties of the
prepared powder blend formulae. The values obtained for the bulk
densities of the prepared Meloxicam powder blend ranged from
0.417 (F4 and F7) to 0.500 (F3). While the values obtained for the
tapped densities of the prepared Meloxicam powder blend ranged
from 0.556 (F9) to 0.625 (F3).
b- The Hausner ratio
The Hausner ratio is a value that is correlated to the flowability of a
powder or granular material. The Hausner ratio is measured from
the bulk and tapped densities. The accepted scale of flowability of a
powder was described in USP 30 (2007). The value of the Hausner
ratio was found to give an indication about the flow properties of
solid dispersion. The values less than 1.25 indicate better flowability
than values more than 1.25[32]
.
The values obtained for the Hauser ratio of the prepared Meloxicam
powder blend ranged from 1.178 (F9) to 1.364 (F4), as shown in
table (3). So, the obtained results showed that five formulae have
good flowability while the other four formulae showed passable
flowability.
Ghorab et al.
Int J Pharm Pharm Sci, Vol 7, Issue 2, 283-289
286
The rank order for the calculated values of Hausner ratio was
arranged in descending order as follows: F9 (7.5 % sodium starch
glycolate), F2 (5 % croscarmellose sodium), F1 (2.5 %
croscarmellose sodium), F8 (5 % sodium starch glycolate), F3 (7.5 %
croscarmellose sodium), F5 (5 % crospovidone), F6 (7.5 %
crospovidone), F7 (2.5 % sodium starch glycolate), F4 (2.5 %
crospovidone).
c- Compressibility % (Carr’s index)
Compressibility percent is indirectly related to the relative flow rate,
a compressible material will be less flowable. The value of the
compressibility percent was found to affect the flow properties of
solid materials. The values between 5 and 12 show excellent
flowability; the values between 12 and 16 exhibit good flowability;
the values between 18 and 21 show fair passable flowability; the
values between 23 and 35 exhibit poor flowability; while the values
between 33 and 38 exhibit very poor flowability [32].
The values obtained for compressibility percent of the prepared
Meloxicam powder blend ranged from 15.094 (F9) to 26.667 (F4), as
shown in table (3).
The rank order for the calculated values of compressibility percent
was arranged in descending order as follows: F9 (7.5 % sodium
starch glycolate), F2 (5 % croscarmellose sodium), F1 (2.5 %
croscarmellose sodium), F8 (5 % sodium starch glycolate), F3 (7.5 %
croscarmellose sodium), F5 (5 % crospovidone), F6 (7.5 %
crospovidone), F7 (2.5 % sodium starch glycolate), F4 (2.5 %
crospovidone). It was concluded that the good flowability was seen
in formulae containing sodium starch glycolate followed by
croscarmellose sodium and crospovidone. It was also noticed that as
the concentration of sodium starch glycolate increased from 2.5% to
7.5%, the flow properties of the powder blend increased. So, the
formula (F9) containing 7.5% sodium starch glycolate showed
superior flow properties as compared to other formulae.
Table 1: The suggested formulae of Meloxicam Orodispersible Tablets
Ingredient (mg/tablet)
F1
F2
F3
F4
F5
F6
F7
F8
F9
Meloxicam
15
15
15
15
15
15
15
15
15
Croscarmellose sodium
5
10
15
-
-
-
-
-
-
Crospovido
ne
-
-
-
5
10
15
-
-
-
Sodium starch glycolate
-
-
-
-
-
-
5
10
15
Avicel ph 102
25
25
25
25
25
25
25
25
25
Aspartame
2
2
2
2
2
2
2
2
2
Talc
4
4
4
4
4
4
4
4
4
Magnesium stearate
2
2
2
2
2
2
2
2
2
Mannitol
147
142
137
147
142
137
147
142
137
Total
20
0
200
200
200
200
200
200
200
200
Table 2: The data collected for the angle of repose, the bulk densities and the tapped densities of the Meloxicam powder blend
Formulation Code
Angle of repose (θ)
Bulk density (gm/cm
3
)
Tapped density (gm/cm
3
)
F1
35.18
˚
±0.25
0.4
76±0.005
0.581
±0.002
F2
36.52
˚±0.37
0.47
2±0.004
0.575
±0.008
F3
38.75
˚±0.59
0.500
±0.005
0.625
±0.004
F4
34.51
˚±
0.28
0.417
±0.008
0.568
±0.002
F5
37.42
˚±
0.61
0.4
35±0.007
0.562
±0.005
F6
38
.21
˚±
0.84
0.455
±0.009
0.602
±0.011
F7
37.19
˚±
0.33
0.4
17±0.00
3
0.562
±0.007
F8
34.12
˚±
0.27
0.4
63±0.004
0.575
±0.005
F9
31.96
˚±
0.19
0.47
2±0.003
0.556
±0.002
Table 3: Hausner ratio and Carr’s index of Meloxicam powder blend
Formulation Code
Hausner ratio
Carr’s index
F1
1.221
18.095
F2
1.218
17.925
F3
1.250
20.000
F4
1.364
26.667
F5
1.292
22.609
F6
1.325
24.545
F7
1.348
25.833
F8
1.241
19.444
F9
1.178
15.094
Evaluation of meloxicam orodispersible tablets
In the present investigation, Meloxicam orodispersible tablets
were prepared in nine formulations with varying concentration of
three superdisintegrants: Croscarmellose Sodium (Ac-Di-Sol),
Crospovidone (Polyplasdone XL),) and Sodium starch glycolate
(Primojel). Each was used in three different concentrations (2.5%,
5% and 7.5%). All batches of the tablets were evaluated for
various post compression parameters such as weight variation,
thickness, diameter, hardness, friability, I n-vitro disintegration
time, amount of drug content, wetting time, and water absorption
ratio. Post compression parameters of all formulations are
reported in table (4-6).
The weights of the tablets were between 199.6 to 202.1 mg. The
calculated weight variation was found to be in acceptable weight
variation range stated in the pharmacopeias (±7.5%). The USP
pharmacopeia specified that the tablets < 80 mg, the deviation will
be ± 10%; tablets between 80 – 250 mg, the deviation will be ± 7.5%;
while tablets > 250 mg, the deviation will be ± 5%. All Meloxicam
ODTs formulations passed the weight variation test. Thickness of all
the formulations was between 3.808 to 3.877 mm showings a fairly
uniform tableting. The diameter of all formulations was between
8.071 to 8.08 mm.
The hardness of all formulations was measured in kg/cm
2
. Hardness
of all formulations was in the range of 4.21 to 4.55 kg/cm
2
. The loss
Ghorab et al.
Int J Pharm Pharm Sci, Vol 7, Issue 2, 283-289
287
in total weight of the tablets due to friability was in the range of
0.3718 to 0.7894%. As shown in table (4-6), the friability values of
none of the formulations exceeded 0.88%. The results of friability
indicate that Meloxicam tablets were mechanically stable and could
handle the rigors of transportation and handling.
The results of In vitro disintegration were within the prescribed
limit and comply with the criteria for orally disintegrating tablets.
The values were in the range of 8.3 - 21.9 sec. The rapid
disintegration was seen in the formulation containing sodium starch
glycolate followed by crospovidone and then Crosscarmellose
sodium. It was also noticed that as the disintegrant concentration
increased from 2.5 to 7.5%, the time taken for disintegration was
reduced. Formulations containing crospovidone as
superdisintegrant in which the disintegration time was reduced
upon increasing the concentration up to 5% only and further
increase in crospovidone concentration will increase the
disintegration time was exception from the above rule. Effect of
superdisintegrant concentration at a disintegration time is shown in
fig. (1).
Wetting time is used as an indicator of the ease of tablet
disintegration and corresponds to the time taken for the tablet to
disintegrate when kept motionless on the tongue. The values lie
between 27 to 58.6 sec. Water absorption ratio ranged from 55.16 to
153.46%.
0
5
10
15
20
25
In vitro disintegra tion time (sec.)
F1 F2 F3 F4 F5 F6 F7 F8 F9
Formulations
In vitro disintegration profile of various formulations
Fig. 1: Effect of superdisintegrants on disintegration time of
Meloxicam orodispersible tablets
Percentage drug content of all Meloxicam formulations was found to
be between 98.04 to 99.59%. These values were within the
acceptable limits stated in the pharmacopeias.
Table 4: Quality control tests of formulae containing Crosscarmellose sodium as superdisintegrant
F1
F2
F3
1
-
Weight Variation (mg)
199.565
±
2.161 200.92
±
1.866
201.09
±
1.660
2
-
Thickness (mm)
3.838
±
0.0123 3.816 0.0107
±
3.83 0.0125
±
3
-
Diameter (mm)
8.073 0.0067
±
8.079 0.0057
±
8.079 0.0057
±
4
-
Hardness (kg/cm2)
4.25
±
0.19 4.51
±
0.20 4.40
±
0.19
5
-
Fria
bility (%)
0.7894
0.4113
0.5071
6
-
Disintegration Time (sec.)
21.90
±
0.88
18.00 0.94
±
15.60 0.70
±
7
-
Wetting Time (sec.)
36.40
±
0.8944
32.80 0.8367
±
27.00 0.7071
±
8
-
Water Absorption Ratio (%)
60.80
±
0.53
78.12 3.12
±
90.03 1.16
±
9
-
Drug Content (%)
98.04 0.8864
±
99
.
02±0.5781 99.42 0.6650
±
Table 5: Quality control tests of formulae containing Crospovidone as superdisintegrant
F4
F5
F6
1
-
Weight Variation (mg)
200.765 1.763
±
200.115
±
1.854
200.375
±
1.759
2
-
Thickness (mm)
3.877
±
0.0067 3.85 0.0094
±
3.85 0.0094
±
3
-
Diameter
(mm)
8.08 0.0047
±
8.075 0.0053
±
8.076 0.005
±
4
-
Hardness (kg/cm2)
4.37
±
0.18 4.21
±
0.10 4.55
±
0.24
5
-
Friability
(%)
0.5258
0.4087
0.3737
6
-
Disintegration Time (sec.)
13.30
±
0.82
10.50 0.71
±
11.80 0.79
±
7
-
Wetting Time (sec.)
45.40
±
0.5477
34.60 0.5477
±
43.00
±
2.00
8
-
Water Absorption Ratio (%)
55.16
±
2.74 64.82
±
0.91 78.30 3.14
±
9
-
Drug Content (%)
98.87
±
0.4884
99.59
±0.4669
98.72 1.0706
±
Table 6: Quality control tests of formulae containing sodium starch glycolate as superdisintegrant
F7
F8
F9
1
-
Weight Variation (m
g)
202.065 1.969
±
200.88
±
1.607
201.815
±
2.488
2
-
Thickness (mm)
3.842
±
0.0114 3.808 0.0063
±
3.815 0.0135
±
3
-
Diameter (mm)
8.071 0.0074
±
8.071 0.0074
±
8.076 0.0097
±
4
-
Hardness (kg/cm2)
4.55
±
0.21 4.48
±
0.22 4.34
±
0.24
5
-
Friability (%)
0.6768
0.4132
0.3718
6
-
Disint
egration Time (sec.)
9.80
±
0.63
8.90 0.74
±
8.30 0.82
±
7
-
Wetting Time (sec.)
34.00
±
0.7071
42.60 1.8166
±
58.60
±
1.1402
8
-
Water Absorption Ratio (%)
88.80 3.23
±
130.98
±
7.39 153.46 2.42
±
9
-
Drug Content (%)
99.10
±
0.2335
98.99
±0.8866
98.88
±
0.9430
Ghorab et al.
Int J Pharm Pharm Sci, Vol 7, Issue 2, 283-289
288
In-vitro dissolution studies
All the nine formulations of Meloxicam ODTs were subjected to In-
vitro dissolution studies by using phosphate buffer pH 7.4 as
dissolution medium. In-vitro release studies of all nine formulations
were plotted and shown in the fig. (2).
In vitro dissolution profile of all formulations
0
20
40
60
80
100
120
0 2 4 6 8 10 12 14 16 18 20
Time (min.)
% drug release
F1
F2
F3
F4
F5
F6
F7
F8
F9
Fig. 2: In vitro dissolution profile of the prepared Meloxicam
formulations
Meloxicam formulae (F1, F4 and F7) which contain 2.5%
superdisintegrant concentration release 85.75%, 95.88% and
95.57%, respectively, at the end of six minutes. An increase in drug
release was observed when 5% superdisintegrant concentration
was used in Meloxicam formulae (F2, F5 and F8). The drug release
was found to be 86.99 %, 98.66% and 98.18%, respectively, at the
end of six minutes. Upon further increasing the superdisintegrants
concentration up to 7.5% in Meloxicam formulae (F3, F6 and F9), it
was found that the drug release becomes 92.65%, 95.75% and
100%, respectively, at the end of six minutes.
It was noticed that as the disintegrant concentration increased from
2.5 to 7.5%, the drug is released rapidly from the formulae.
Formulations containing crospovidone as superdisintegrant in
which the drug release was increased upon increasing the
concentration up to 5% only and further increase in crospovidone
concentration will decrease the release was exception from the
above rule.
The rapid drug release was observed in the formulation containing
sodium starch glycolate followed by crospovidone and then
croscarmellose sodium. Among all the formulated tablets, F9 which
contains 7.5% sodium starch glycolate as superdisintegrant gave the
highest dissolution (100%) at the end of six minutes. The rapid drug
dissolution might be due to easy breakdown of particles and rapid
absorption of drug into the dissolution medium. In all nine
formulations the dug release was almost up to 90 – 100 %, after ten
minutes.
From the total rank order shown in table (7), formula F9 which
contain 7.5 % sodium starch glycolate was found to be the best
formula from the tested Meloxicam ODTs. This formula acquires the
best Micromeritic properties, the higher values for Meloxicam
quality control tests and the best In-vitro drug release.
Table 7: Rank order of different formulae depending on Micromeritic properties, quality control tests and In vitro release study
Formula Number
F1
F2
F3
F4
F5
F6
F7
F8
F9
Micromeritic properties
3
2
5
7
5
8
8
3
1
Quality control tests
9
6
2
8
2
7
5
4
1
In vitro
drug release
9
8
7
6
2
5
4
2
1
Total
21
16
14
21
9
20
17
9
3
Final Rank Order
8
5
4
8
2
7
6
2
1
CONCLUSION
Orodispersible tablets of Meloxicam were prepared by direct
compression method using Croscarmellose Sodium (Ac-Di-Sol),
Crospovidone (Polyplasdone XL),) and Sodium starch glycolate
(Primojel) as superdisintegrant. The tablets disintegrated rapidly in
oral cavity and had acceptable hardness and friability. In vitro drug
release from the tablets shows significantly improved drug
dissolution. Hence it could be concluded that the superdisintegrant
based orodispersible tablets of Meloxicam would be quite effective,
providing quick onset of action without need for water for
swallowing or administration.
ACKNOWLEDGEMENT
The authors are very much thankful to MUP, EIPICO and Amoun
pharmaceutical companies for providing gift samples of Meloxicam
and other excipients that facilitate to carry out this work.
CONFLICT OF INTERESTS
Declared None
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