See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/280097669

Pharmaceutical

Research · July 2015

DOI: 10.13140/RG.2.1.4442.4801

CITATIONS READS
0 1,513

1 author:

Nareshkumar Kothapally
Helmholtz-Zentrum Hereon
1 PUBLICATION 0 CITATIONS

SEE PROFILE

All content following this page was uploaded by Nareshkumar Kothapally on 17 July 2015.

The user has requested enhancement of the downloaded file.

 Kothapally Naresh Kumar et al. Int. Res. J. Pharm. 2013, 4 (11)
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY
www.irjponline.com ISSN 2230 – 8407
Research Article

FORMULATING TASTE-MASKED ORALLY DISINTEGRATING TABLETS OF A BITTER DRUG IBUPROFEN

Kothapally Naresh Kumar*, Devareddy Sandeep
Care college of pharmacy, Affiliated to Kakatiya University, Oglapur, Atmakur mandal, Andhra Pradesh, India
*Corresponding Author Email: sandeep1987s@gmail.com

Article Received on: 30/09/13 Revised on: 11/11/13 Approved for publication: 20/11/13

DOI: 10.7897/2230-8407.041117
IRJP is an official publication of Moksha Publishing House. Website: www.mokshaph.com
© All rights reserved.

ABSTRACT
This study is aimed at formulating taste-masked orally disintegrating tablets of a bitter drug i.e., Ibuprofen. Taste masking was carried out by fluid bed coating
of extruded and spheronized pellets comprising of Ibuprofen, microcrystalline cellulose and lactose. Two marketed taste-masking systems, namely Eudragit
EPO and Opadry tm were evaluated. For the formulation of orally disintegrating tablets a range of excipients such as super disintegrants, diluents, sweeteners
and flavours were evaluated and a prototype formulation was selected. This prototype formulation had Eudragit EPO coated taste masked pellets and selected
excipients. Its disintegration time was found to be about 8 seconds. Tablets were evaluated for their taste, disintegration time, hardness, friability, water uptake
and drug release profile. It was concluded from this study that water insoluble, water permeable polymer system like Eudragit EPO can effectively taste mask
bitter drugs without unduly affecting their drug release profile. As per objective of the work, the formulation was found to have a disintegration time of less
than 30 seconds (about 8 seconds), had good mouth feel and organoleptic properties. With Eudragit EPO the bitterness and burning sensation of drug was
significantly masked at low coating levels (15 %) without affecting the Ibuprofen release.
Keywords: Ibuprofen, Eudragit, Taste masking, Bitter.

INTRODUCTION Bulk Density

Oral Drug Delivery It’s a measurement to describe packing of particles. Bulk
Oral drug delivery is the most desirable and preferred method density/apparent density are used to determine the amount of
of administering therapeutic agents for their systemic effects. drug that occupies the volume (g/ml).
In addition, the oral medication is generally considered as the
r
first avenue investigated in the discovery and development of b = m / Vb

new drug entities and pharmaceutical formulations, mainly Where rb = bulk density, m = mass of the blend, Vb = untapped volume
because of patient acceptance and convenience in
administration.1 Oral dosage form is the most popular route Determination of Bulk density
for drug therapy. Over 80 % of the drugs formulated to Weighed quantity of Ibuprofen (25g) was transferred into 100
produce systemic effects in the United States are produced as ml measuring cylinder without tapping during transfer. The
oral dosage forms. Compared to other oral dosage forms, volume occupied by the drug was measured. Bulk density
tablets are the manufacturer’s dosage form of choice because was measured by using formula
of their relatively low cost of manufacture, package, and r
shipment. b = m / Vb.
The values obtained are reported in the table.
Taste Masking of Oral Pharmaceuticals
Taste masking is of critical importance for active ingredients Tapped density
with an unpleasant bitter taste, due to the need for increased 25 g of Ibuprofen was taken in 100 ml measuring cylinder
patient compliance. Taste masking technology involves the that was placed in Electro lab tapped density apparatus
development of a system that prevents the active substance (method USP-I). Initial volume (V0) of the cylinder was
interacting with the taste buds, thereby eliminating or noted and then the cylinder was tapped 500 times and volume
reducing the negative sensory response. There are three was measured. Then further an additional 750 tapings were
general tastes masking principles, the use of a physical repeated. No difference was noted between the volumes of
barrier, chemical or solubility modification, and solid the two tapings (500 and 750). The final volume (V) was
dispersions, each of them further subdivided into several considered after completion of 750 taps. Tapped density was
methods. Additionally, unique platforms such as orally measured by using formula
disintegrating and chewable tablets, applicable for taste
r
masking have been extensively employed. Taste masking of t = m / Vt.
drug may be achieved with preventing the exposure of drug The values obtained are reported in the Table3,4.
to the tongue through processing or adding competing taste-
masking agents. Exposure of solubilized drug to the oral Compressibility Index
cavity can be prevented by encapsulation in polymer systems Weighed amount of Ibuprofen (25g) was transferred to 100
or complexation2. ml-graduated cylinder and subjected to 500,750 and1250 taps
in tap density tester (Electro lab). The difference between two
MATERIALS AND METHODS taps should be less than 2 %. The % of compressibility index
Pre Formulation – API Characterization calculated using formula
Compressibility Index = 100 * (rtapped -rbulk) / rtapped

Page 71
 Kothapally Naresh Kumar et al. Int. Res. J. Pharm. 2013, 4 (11)
Hausner’s ratio · Ingredients of Step 1 were blended in a poly bag for 10
It is measurement of frictional resistance of the drug .the minutes.
ideal range should be 1.2 –1.5.it is the determined by the ratio · Ingredients of Step 2 were added to the blended material
of tapped density and bulk density. and mixed for 5 minutes.
· Compressed the material of step 5 materials into
Hausners ratio = rtapped / rbulk biconvex, round shaped tablets using 11 mm punch at 3.0
± 0.5 kp (Table 4).
Angle of repose
It is defined as the maximum angle that can be obtained Selection of disintegrant in the formulation
between the free standing of powder heap and horizontal Procedure
plane, which is given by the equation: · API, disintegrant(s), diluent, and lubricant were sifted
through ASTM #40 separately.
q = tan-1 h / r
· Glidant, flavour and sweetener were sifted through
Where q = Angle of repose, h = Height of the pile,
r = Radius of the base of the conical pile ASTM #60.
· All ingredients were weighed accurately.
Procedure · Ingredients of Step 1 except lubricant were blended in a
Weighed quantity of the drug was passed through a funnel poly bag for 10 minutes.
kept at a height 2 cm from the base. The powder is passed till · Ingredients of Step 2 and lubricant were added to the
it forms a heap and touches the tip of the funnel. The radius blended material and mixed for 5 minutes.
was measured and angle of repose was calculated by using · Compressed the material of step 5 materials into
the above formula5,6. biconvex, round shaped tablets using 11 mm punch at 3.0
From the results in Table 1, it is evident that the drug has ± 0.5 kp (Table 5 & 6).
very poor flow properties, as the compressibility index,
Hausner’s ratio and Angle of repose values are high. Taste Masking Methods
Taste is one of the most important parameters governing
Particle size distribution patient compliance. Undesirable taste is one of the several
Ibuprofen was analyzed for particle size distribution by important formulation problems that encounters with certain
means of mechanical sieve shaker (Retsch) Table 2. drugs. So, any pharmaceutical formulation with a pleasing
taste would definitely be preferred over a competitor’s
Construction of calibration curve of Ibuprofen product that would translate into better patient compliance
Standard curve of Ibuprofen was prepared in pH 7.2 and therapeutic value for the patient and more business and
phosphate buffer and in 0.1 N HCl. profits for the company. In the present scenario, bitterness of
the Ibuprofen was observed in the formulated ODT tablets.
Procedure for construction of calibration curve of So the challenge was to achieve a taste masked fast-
Ibuprofen in pH 7.2 phosphate buffer disintegrating dosage form for the drug7,8. Following
Preparation of stock solution strategies were used to mask bitterness of Ibuprofen.
100 mg of the drug is accurately weighed and transferred into
a 100 ml volumetric flask. 7.2 pH phosphate buffer was Organoleptic Modification
added to it so as to dissolve the drug and finally diluted up to Shown in Table 7-9
the mark to give 1000 μg/ml.
Evaluation of Tablets
Preparation of dilutions Physical properties
Different dilutions were made using the stock solution The surface of the formulated tablets was evaluated to ensure
prepared. 0.5, 1, 1.5, 2, 2.5 ml of stock solution was taken that there was no capping, lamination, sticking or other
and diluted to 100 ml of pH 7.2 phosphate buffer to get the defects during compression. The tablet surface should be
concentrations of 5, 10, 15, 20 and 25 μg/ml. The absorbance smooth, and color should be white since no color is used in
of above solutions was measured in UV-spectrophotometer at formulation and all ingredients were white in color. If color
221 nm wavelength. Plot the graph between the concentration and odor of the tablet changes, it may be the indication of any
(μg/ml) on x-axis and absorbance (nm) on y-axis as shown in chemical reaction that may effect the properties of
Figure 1. (Table 3) formulation.

Formulation Development Weight variation

Selection of formulation method Weight variation test was performed according to USP.
Orally disintegrating tablets of Ibuprofen were formulated Average weight of twenty tablets was calculated and
using direct compression method. individual weight of each tablet was taken. % deviation was
calculated with respect to average weight. The maximum %
Direct Compression deviation allowed is 5 % as the tablet weight is more than
Procedure 324 mg. the tablets meet the USP test if no more than two
· API, disintegrant, diluent, and lubricant was sifted tablets are outside the % limit and if no tablet differs by more
through ASTM #40 separately. than two times the % limit.
· Glidant, flavour, sweetener were sifted through ASTM
#60. Thickness
· All ingredients were weighed accurately. The thickness in millimeters (mm) was measured
individually for 10 pre weighed tablets by using a Mitutoyo

Page 72
 Kothapally Naresh Kumar et al. Int. Res. J. Pharm. 2013, 4 (11)
portable dial hand micrometer. The average weight, standard completely wet them was noted as the wetting time. These
deviation and relative standard variation were reported. measurements were carried out in replicates of six. Wetting
time was recorded using a stopwatch.
Hardness
This test gives the indication for the tablets ability to with Water absorption Ratio (R)
stand its integrity of drug with the drug release can be The weight of the tablet prior to placement in the petridish
optimized. It was determined by placing the tablet between was noted (Wb) using a Shimadzu digital balance. The wetted
the anvils only one of which is movable, driven by electricity. tablet was removed and reweighed (Wa). Water absorption
It presses the tablet at constant load till the tablet breaks. It ratio, R, was then determined according to the following
was recorded in KP (1kP = 1 kg). Hardness of 10 tablets equation9-11.
determined and average hardness and range was calculated.
R = 100 * (Wa - Wb) / Wb
Friability
Where Wb and Wa were tablet weights before and after water absorption,
Friability is related to tablets ability to withstand both shocks respectively
and abrasion without crumbling during manufacturing,
packing, transportation and consumer handling. Friability can In vitro Disintegration test
be evaluated by means of friability test apparatus. This test provides determination for compliance with the
Compressed tablets that loose less than 0.5 % to 1.0 % in limits on disintegration. The purpose of the test,
weight are generally considered acceptable. Friability of the disintegration does not comply complete solution of the unit
formulated tablets was determined in Roche friabilator. Ten or even of its active constituents. Complete disintegration is
tablets were weighed accurately and then initial weight was defined as that state in which any residue of the unit,
note down. There are introduced in the apparatus and remaining on the screen of the test apparatus is a soft mass
subjected to 100 revolutions at a speed of 25 rpm for 4 having no palpability firm core. Electro lab disintegration
minutes. When the drum stopped, tablets were taken and apparatus was used where one tablet was placed in each of
dedusted and final weight was taken. % Friability was the 6 tubes of the basket. Operated the apparatus using water
calculated by the formula as media at 37° ± 0.5°C as the immersion liquid12. The time
of disintegration was noted.
Initial weight (g) – Final weight (g)
% Friability = ---------------------------------------------------- × 100
Initial weight (g) In-vitro release study
Dissolution
Acceptance criteria: the friability value should be less than 1.0 % Dissolution was done for each batch of Taste masked orally
disintegrating tablets of Ibuprofen in pH 7.2 Phosphate buffer
Taste Evaluation for 1 h.
The taste characteristic of taste masked ODT Formulations
was compared in healthy human volunteers, from whom Dissolution conditions
informed consent was first obtained. The subjects were Dissolution media – pH 7.2 Phosphate buffer
informed of the purpose and protocol of the study. As per the Apparatus – USP II (Paddle)
protocol all volunteers were asked to rinse their mouth with Volume – 900 ml
distilled water prior to the test. The formulated Opadry tm rpm – 100
and Eudragit EPO drug coated ODT Tablets were given to 10 Temp. – 37 + 0.5o C
healthy volunteers and were compared with the uncoated Sampling points – 5, 10, 15, 20, 30, 45, 60 minutes.
ODT Tablets. Samples equivalent to 100 mg drug were given
to the 10 volunteers. Bitterness was recorded immediately Preparation of sample dilutions
according to the bitterness intensity scale from 0 to 3; 3 being 3.0 ml of sample which is filtered through 0.45 µm filters
strongest, 2 being moderate, 1 being slight, and 0 for no was taken and diluted to 20 ml using pH 7.2 Phosphate buffer
bitterness taste. The volunteers were asked to rank to give the concentration of 15 µg/ ml.
accordingly based on the evaluation of the given samples.
Preparation of standard solution
Wetting Time 55 mg of drug was dissolved in 100 ml of pH 7.2 Phosphate
Five circular tissue papers were placed in a petridish of 10 cm buffer and from this solution 3 ml was taken and diluted to
diameter. Ten millimeters of water was added to the 100 ml. Analysis of samples was done by using UV
petridish. A tablet was carefully placed on the surface of the Spectrophotometer at 221 nm wavelength.
tissue paper in the petridish at 250C. The time required for
water to reach the upper surface of the tablets and to

Cumulative percentage drug release = Absorbance test × Dilutionstd × Drug purity × 100
Absorbancestd × Dilutiontest × label claim ×100
Corrected cumulative percentage drug release = Cumulative percentage drug release + Correction factor
Correction Factor = Vol of sample taken × % drug released at previous time point × 100
Percentage drug release at that time point

Different dissolution profiles were compared to establish the In-vivo Disintegration Time
effect of formulation or process variables on the drug release. The formulated Opadry tm and Eudragit EPO Ibuprofen
coated tablets were given to 10 healthy volunteers and were
compared with the uncoated pellets. The subjects were
informed of the purpose and protocol of the study. As per the

Page 73
 Kothapally Naresh Kumar et al. Int. Res. J. Pharm. 2013, 4 (11)
protocol all volunteers were asked to rinse their mouth with volunteer to feel that the last noticeable granule had
distilled water prior to the test. Tablets were placed on the disintegrated in the oral cavity was considered as the in vivo
tongue and a stopwatch was started immediately. Volunteers DT. This experiment was conducted in all 10 subjects and the
were allowed to move the tablet against the upper palate of mean ± SD were calculated for each13.
the mouth with their tongue and cause a gentle tumbling
action on the tablet without chewing it. Time taken for the

Figure 1: Calibration curve of Ibuprofen in pH 7.2 phosphate buffer (λmax = 221 nm)

Table 1: Flow properties of Ibuprofen

Parameters
Bulk density 0.378 g/cc
Tap density 0. 609 g/cc
Compressibility / Carr’s index (%) 38 %
Hausner’s ratio 1.61
Angle of repose 49.57

Table 2: Particle size distribution

Sieve No. Sieve size (micron) Initial Wt. (g) Final Wt. (g) % Retained
#80 180 269.5 269.5 0
#100 150 247.5 248.0 2
#140 106 268.5 279.0 42
#200 75 238.0 250.5 50
#230 63 239.0 240.5 6
Collector 343.5 343.5 0
Total 100

Table 3: Calibration data of Ibuprofen in pH 7.2 Phosphate buffer Table 4: Formulation of drug by direct compression

Concentration (μg/ml) Absorbance Ingredients F001

0 0.0 Quantity (mg / Tab)
2 0.0914 Ibuprofen (20 %) 100.0
4 0.1763 Pearlitol SD 200 (73.75 %) 358.75
6 0.2699 Ac – Di – Sol (5 %) 25.0
8 0.3559 Sodium stearyl fumarate (0.5 %) 2.5
10 0.4451 Aerosil (0.25 %) 1.25
12 0.5198 Orange flavor (0.5 %) 2.5
Acesulfame potassium (2 %) 10.0
Total 500.0

Table 5: Selection of disintegrants and selected disintegrant concentration

Ingredients Quantity (mg / Tab)

Disintegrant selection Disintegrant concentration selection
F001 F002 F003 F004 F005 F006
Ibuprofen (20 %) 100 100 100 100 100 100
Pearlitol SD 200 358.75 358.75 358.75 358.75 368.75 348.75
Super disintegrant 25.0 25.0 25.0 25.0 15.0 35.0
Sodium stearyl fumarate (0.5 %) 2.5 2.5 2.5 2.5 2.5 2.5
Aerosil (0.25 %) 1.25 1.25 1.25 1.25 1.25 1.25
Orange flavor (0.5 %) 2.5 2.5 2.5 2.5 2.5 2.5
Acesulfame potassium (2 %) 10.0 10.0 10.0 10.0 10.0 10.0
Total 500 500 500 500 500 500
F001 – 5 % Ac-Di-Sol, F002 – 5 % Polyplasdone XL, F003 – 5 % Sodium starch glycolate, F004 – 5 % L-Hydroxy propyl cellulose
F005 – 3 % Polyplasdone XL, F006 – 7 % Polyplasdone XL

Page 74
 Kothapally Naresh Kumar et al. Int. Res. J. Pharm. 2013, 4 (11)
Table 6: Selection of diluents

Ingredients F002 F007

Quantity (mg / tab)
Ibuprofen (20 %) 100.0 100.0
Pearlitol SD 200 (73.75 %) 358.75 358.75
Ac – Di – Sol (5 %) 25.0 25.0
Sodium stearyl fumarate (0.5 %) 2.5 2.5
Aerosil (0.25 %) 1.25 1.25
Orange flavor (0.5 %) 2.5 2.5
Acesulfame potassium (2 %) 10.0 10.0
Total 500.0 500.0

F002 – Pearlitolâ SD 200 (Insoluble), F007 – Lactose monohydrate [Tablettose 80] (Soluble)

Table 7: Selection of flavours and sweeteners

Ingredients Quantity (mg / Tab)

Flavour selection Sweetener selection
F008 F009 F010 F011 F012
Ibuprofen (20 %) 100 100 100 100 100
Pearlitol SD 200 311.25 336.25 328.75 338.25 330.25
Superdisintegrant (5 %) 25.0 25.0 25.0 25.0 25.0
Sodium stearyl fumarate (0.5 %) 2.5 2.5 2.5 2.5 2.5
Aerosil (0.25 %) 1.25 1.25 1.25 1.25 1.25
Orange flavor (6 %) 30 - - - -
Peppermint flavor (1 %) - 5 - - 5
Grape flavor (2.5 %) - - 12.5 - -
Lemon flavor (0.6 %) - - - 3 -
Acesulfame potassium (6 %) 30.0 30.0 30.0 30.0 -
Aspartame (7.2 %) - - - - 36.0
Total 500 500 500 500 500

F008 – Orange flavor and Acesulfame potassium sweetener, F009 – Peppermint flavor and Acesulfame potassium sweetener, F010 – Grape flavor and
Acesulfame potassium sweetener, F011 – Lemon flavor and Acesulfame potassium sweetener, F012 – Peppermint flavor and Aspartame sweetener

Table 8: Process parameters

S. No Parameters Limits
1 Spray gun Pam Glatt Top spray gun
2 Blower drive speed (%) 45 – 55
3 Inlet air temperature (°C) 30 – 35
4 Product temperature (°C) 35 – 40
5 Atomization air pressure (bar) 1.5
6 Spray pump speed (rpm) 1.0
7 Filter shaking mode Asynchronous
8 Filter shaking interval (sec) 8
9 Filter shaking pause (sec) 60

Table 9: Granulation of Ibuprofen using PVP K - 30 as binder Table 10: Physical evaluation of tablets

S. Ingredients Quantity F001

No. (g) Colour White
1 Ibuprofen 300 Surface Smooth
(95.23 %) Thickness (mm) 4.48 ± 0.2
2 Povidone K – 15 Hardness (kP) 3.0 ± 0.5
30 (4.77 %) Weight (mg) 500 ± 1.0
3 Purified water q.s Assay (%w/w) 99.98
D.T. (sec) 27.5 ± 1.45
Friability (%) 1.19 ± 0.37

F001 – 5 % Ac-Di-Sol

Table 11: Physical evaluation of tablets

F002 F003 F004 F005 F006

Colour White White White White White
Surface Smooth Smooth Smooth Smooth Smooth
Thickness(mm) 4.45 ± 0.3 4.43 ± 0.3 4.42 ± 0.3 4.48 ± 0.3 4.43 ± 0.3
Hardness (kP) 3.0 ± 0.5 3.0 ± 0.5 3.0 ± 0.5 3.0 ± 0.5 3.0 ± 0.5
Weight (mg) 500 ± 1.2 500 ± 1.3 500 ± 1.6 500 ± 1.0 500 ± 1.5
Assay (%w/w) 101.6 ± 1.1 98.86 ± 0.9 99.76 ± 2.0 98.5 ± 1.3 100.2 ± 1.7
D.T. (sec) 12.1 ± 1.1 42.2 ± 2.3* 35.8 ± 1.66* 13 ± 0.9 15 ± 1.7
Friability (%) 1.15 ± 0.2 1.31 ± 0.5 1.25 ± 0.21 1.19 ± 0.5 1.09 ± 0.9

*Since D.T does not meet intended time of 30 sec, it fails.

F002 – 5 % Polyplasdone XL, F003 – 5 % Sodium starch glycolate, F004 – 5 % L-Hydroxy propyl cellulose, F005 – 3 % Polyplasdone XL, F006 – 7 %
Polyplasdone XL

Page 75
 Kothapally Naresh Kumar et al. Int. Res. J. Pharm. 2013, 4 (11)

Table 12: Physical evaluation of tablets

F002 F007
Colour White White
Surface Smooth Smooth
Thickness (mm) 4.45 ± 0.3 4.43 ± 0.3
Hardness (kP) 3.0 ± 0.5 3.0 ± 0.5
Weight (mg) 500 ± 1.2 500 ± 1.8
Assay (%w/w) 101.6 ± 1.1 99.75 ± 1.3
D.T. (sec) 12.1 ± 1.1 11.8 ± 0.7
Friability (%) 1.15 ± 0.2 1.22 ± 1.4

F002 – Pearlitolâ SD 200 (Insoluble), F007 – Lactose monohydrate [Tablettose 80] (Soluble)

Table 13: Physical evaluation of tablets

F008 F009 F010 F011 F012

Colour White White White White White
Surface Smooth Smooth Smooth Smooth Smooth
Thickness(mm) 4.44 ± 0.3 4.45 ± 0.3 4.43 ± 0.3 4.44 ± 0.3 4.45 ± 0.3
Hardness (kP) 3.0 ± 0.5 3.0 ± 0.5 3.0 ± 0.5 3.0 ± 0.5 3.0 ± 0.5
Weight (mg) 500 ± 1.2 500 ± 1.8 500 ± 1.6 500 ± 2.0 500 ± 1.0
Assay (%w/w) 100.1 ± 1.4 99.33 ± 0.5 100.7 ± 0.9 99.8 ± 1.7 101.3 ± 2.0
D.T. (sec) 12.8 ± 1.9 12.3 ± 1.2 12.5 ± 1.6 12.2 ± 1.5 12.6 ± 1.7
Friability (%) 1.19 ± 0.9 1.33 ± 1.6 1.26 ± 1.9 1.11 ± 0.6 1.23 ± 1.4

F008 – Orange flavor and Acesulfame potassium sweetener, F009 – Peppermint flavor and Acesulfame potassium sweetener, F010 – Grape flavor and
Acesulfame potassium sweetener, F011 – Lemon flavor and Acesulfame potassium sweetener, F012 – Peppermint flavor and Aspartame sweetener

Table 14: Selection of orally disinterating tablets containing different flavors

Volunteer Flavours
Orange Peppermint Grape Lemon
A B G A B G A B G A B G
1 √ √ √ √
2 √ √ √ √
3 √ √ √ √
4 √ √ √ √
5 √ √ √ √
6 √ √ √ √
7 √ √ √ √
8 √ √ √ √
9 √ √ √ √
10 √ √ √ √

A – Average, B – Better and G – Good

Table 15: Selection of orally disintegrating tablets with different

sweeteners
Table 16: Physical evaluation of tablets
Volunteer Sweeteners
Acesulfame Potassium Aspartame Uncoated tablet F013
A B G A B G Colour Off white Off white
1 √ √ Surface Smooth Smooth
2 √ √ √ Thickness (mm) 4.45 ± 0.3 4.49 ± 0.3
3 √ √ Hardness (kP) 3.0 ± 0.5 3.0 ± 0.5
4 √ √ Weight (mg) 500 ± 1.0 500 ± 1.0
5 √ √ Assay (% w/w) 100.16 ± 1.1 98.79 ± 2.1
6 √ √ D.T. (sec) 8.5 ± 1.5 8.6 ± 1.67
7 √ √ Friaibility (%) 1.38 ± 0.5 1.39 ± 1.4
8 √ √ Wetting time 15.7 ± 0.8 15.3 ± 0.8
9 √ √ Water absorption ratio 55.36 55.85
10 √ √
F013 – Opadry tm coated Ibuprofen MCC tablet
A – Average, B – Better and G – Good

Page 76
 Kothapally Naresh Kumar et al. Int. Res. J. Pharm. 2013, 4 (11)
Table 17: % Cumulative drug release of Opadry coated tablet
Table 18: Physical evaluation of tablets
Time (minute) Uncoated tablet F013
5 35.26 30.23 Uncoated tablet F015
10 47.80 40.19 Colour Off white Off white
15 58.63 53.56 Surface Smooth Smooth
20 67.60 62.60 Thickness (mm) 4.47 ± 0.3 4.48 ± 0.3
30 89.53 82.53 Hardness (kP) 3.0 ± 0.5 3.0 ± 0.5
45 95.86 91.66 Weight (mg) 500 ± 1.0 500 ± 1.5
60 99.30 97.33 Assay (%w/w) 99.51 ± 0.5 100.61 ± 1.7
D.T. (sec) 8.4 ± 1.9 8.3 ± 1.92
F013 – Opadry tm coated Ibuprofen MCC tablet Friaibility (%) 1.45 ± 0.45 1.35 ± 0.8
Wetting time 15.2 ± 0.9 15.8 ± 1.2
Water absorption ratio 55.03 55.83

F015 – Eudragit EPO coated Ibuprofen MCC lactose tablet

Table 19: % Cumulative drug release of Eudragit EPO coated tablet and Marketed product

Time (minute) Uncoated tablet F015 Marketed product

5 49.03 34.43 88.32
10 66.23 51.46 90.91
15 78.66 63.03 91.29
20 84.90 76.60 91.68
30 96.36 89.26 91.81
45 98.33 94.60 91.94
60 99.06 98.43 95.18

Table 20: Dissolution parameters

Formulation Dissolution parameters

DP30min %DE60min T50% t75% t90%
F013 82.53 69.33 14 27 41
F014 77.32 65.72 16 28 47
F015 89.26 75.92 9 20 31
Market 91.81 84.49 2 3 13

DP – Percent drug released at particular time, % DE – Percent dissolution efficiency at particular time, t50% – Time taken to release 50% Ibuprofen, t75% – Time
taken to release 75 % Ibuprofen, t90% – Time taken to release 90% Ibuprofen, F013 – Opadry tm coated Ibuprofen MCC tablet, F014 – Eudragit EPO coated
Ibuprofen MCC tablet, F015 – Eudragit EPO coated Ibuprofen MCC lactose tablet

Table 21: Taste panel study

Formulation Degree of bitterness after time

10 seconds 1 minutes 5 minutes 10 minutes
Uncoated tablet 2 3 3 3
F013 1 1 1 1
F015 0 0 0 0

RESULTS AND DISCUSSION Taste Masking Strategies

Selection of formulation method Burning sensation of the Ibuprofen in throat was observed in
ODT tablets of Ibuprofen were formulated using Ac – Di – the formulated ODT tablets (F002). So to mask the
Sol as disintegrant by direct compression method (F001). The unacceptable taste of Ibuprofen a taste masked fast-
D.T. observed for this formulation was 27.5 seconds. To disintegrating dosage form must be formulated. Taste
decrease the D.T. of the formulation further, a study was masking of the drug was carried out by two simpler
performed using different disintegrants. (Table 10-11) techniques viz., organoleptic modification and fluidized bed
coating (physical barrier). Although many other techniques
Selection of diluents in the formulation were popular for taste masking like, usage of b -
The effect of filler was optimized by using Pearlitolâ SD 200 cyclodextrins, Ion-exchange resins (complexation), solid
(Insoluble – F002) and Lactose monohydrate – Tablettose 80 dispersions like melt extrusion, spray congealing etc. these
(Soluble – F007). (Table 12) two methodologies were chosen because the final dosage
Lactose monohydrate showed a lesser disintegration time of form that is to be formulated is for an OTC drug and hence it
11.8 seconds when compared to that of Pearlitolâ SD 200. must be cost – effective. Usage of b - cyclodextrins in the
But when taken in vivo the mouth feel of Pearlitol â SD 200 formulation increases the cost of final dosage form. Usage of
was better than that of Lactose monohydrate as it exhibits ion exchange resins might increase the contact time between
negative heat of solution. So, Pearlitolâ SD 200 (F002) was the drug species and the ion exchange resin and more over it
selected for further trials. More over the Ibuprofen showed also depends on the degree of crosslinking. So taste masking
bitter taste. Hence, trials for reduction of bitterness were by organoleptic modification and fluidized bed coating were
further carried out. selected as these two methods are simpler and feasible.

Page 77
 Kothapally Naresh Kumar et al. Int. Res. J. Pharm. 2013, 4 (11)
Organoleptic Modification – Flavors, Sweeteners taste mask bitter drugs without unduly affecting their drug
The drug used in the formulation is a bitter / unpleasant release profile. Coating of Ibuprofen loaded MCC pellets
tasting pharmaceutical agent. An attempt was made to with Eudragit EPO had masked the taste but to increase the in
suppress the bad taste using different flavors and sweeteners. vitro drug release the pellet composition was changed.
Flavors for taste masking of bitter drugs such as orange, Ibuprofen release from MCC pellets involves mechanism of
peppermint, lemon, grape flavors were used. Aspartame and erosion and diffusion which is a slower process than
Acesulfame potassium sweeteners were used. The results of dissolution and diffusion. Therefore to ensure faster drug
the formulations were given in Table 13. release, a water soluble excipient, lactose was added to the
10 healthy human volunteers were selected to give ranking pellets. Coating of Ibuprofen loaded MCC-Lactose pellets
for the taste masking effect produced in the ODTs containing with Eudragit EPO masked the taste and increased the drug
different flavors i.e., orange, peppermint, grape and lemon release profile by 12 % in 30 minutes. As per objective of the
flavors. (Table 14) work, the formulation was found to have a disintegration time
5 volunteers ranked better for orange flavor. 6 volunteers of less than 30 seconds (about 8 seconds), had good mouth
ranked better and 1 volunteer ranked good for peppermint feel and organoleptic properties. With Eudragit EPO the
flavor. 4 volunteers ranked better for grape and lemon bitterness and burning sensation of drug was significantly
flavors. So, peppermint flavor was selected and incorporated masked at low coating levels (15 %) without affecting the
in further formulations. Slight taste masking was observed Ibuprofen release. Also this method of fluidized bed coating
with Peppermint flavor when compared to other flavors. So, a for taste masking and formulation of orally disintegrating
trial was taken by changing the sweetener (Aspartame) in the tablets by conventional tablet methods could be industrially
formulation. (Table 15) scalable with further optimization studies.
7 volunteers ranked good for Acesulfame potassium. 8
volunteers ranked good for Aspartame. So, Aspartame was REFERENCES
selected and incorporated in further formulations. Rankings 1. Bonadeo D, Ciccarello F, Pagano A. Process for the preparation of
granulates suitable to the preparation of rapidly disintegratable mouth-
given by the human volunteers showed that Aspartame was soluble tablets and compositions obtained thereby. US Patent 6, 316,
better than Acesulfame potassium but significant taste 029; 1998.
masking was not observed even with Aspartame sweetener. 2. Eoga AB, Valia KH. Method for making fast-melt tablets. US Patent 5,
As taste masking by organoleptic modification did not work 939, 091; 1999.
3. www.pua.cc/PUASite
out, drug-coating trials were further carried out. 4. Shyamala B, Narmada GY. Rapid dissolving tablets: A novel dosage
form. The Indian Pharmacist 2002; 13(8): 09-12.
In – vitro evaluation 5. Valleri M, Mura P, Maestrelli F, Cirri M, Ballerini R. Development and
% Cumulative drug release of Opadry tm coated tablet is evaluation of glyburide fast dissolving tablets using solid dispersion
technique. Drug Dev Ind Pharm 2004; 30(5): 525-34.
shown in Table 16-17. http://dx.doi.org/10.1081/DDC-120037483 PMid:15244088
6. Hanawa T, Watanabe A, Tsuchiya T, Ikoma R, Hidaka M, Sugihara M,
In – vitro evaluation New Oral dosage form for elderly patients: Preparation and
Table 18-21 characterization of silk fibroin gel. Chem Pharm Bull 1995; 43(2): 284-
Results are the mean of 10 volunteers observations. 3 – 288. http://dx.doi.org/10.1248/cpb.43.284
7. Mallet L. Caring for the Elderly Patient. J. Am. Pharm. Assoc 1996;
Strongly bitter, 2 – moderate bitterness, 1 – slight bitterness, 36(11): 628-635.
and 0 – no bitter taste. 8. Porter SC. Novel drug delivery: Review of recent trends with oral solid
dosage forms. Am Pharm Rev 2001; 85: 28-35.
CONCLUSION 9. Deepak K. Orally disintegrating tablets. Tablets and Capsules 2004; 7:
30-35.
This study is aimed at formulating taste-masked orally 10. Brown D. Orally disintegrating tablets: Taste over speed. Drug Deliv
disintegrating tablets of a bitter drug i.e., Ibuprofen. Taste Tech 2001; 3(6): 58-61.
masking was carried out by fluid bed coating of extruded and 11. US Food and Drug Administration, CDER Data Standards Manual.
spheronized pellets comprising of Ibuprofen, microcrystalline 2003. www.fda.gov/cder/dsm/DRG/drg00201.htm. Accessed; 2007.
12. Khar Roop K, Sohi Harmik. Taste masking technologies in oral
cellulose and lactose. Two marketed taste-masking systems, pharmaceuticals: Recent developments and approaches. Drug
namely Eudragit EPO and Opadry tm were evaluated. For the Development and Industrial Pharmacy 2004; 30(5): 429-448.
formulation of orally disintegrating tablets a range of http://dx.doi.org/10.1081/DDC-120037477 PMid:15244079
excipients such as super disintegrants, diluents, sweeteners 13. Koizumi K, Watanabe Y, Morita K, Utoguchi N, Matsumoto M. New
method of preparing high-porosity rapidly saliva soluble compressed
and flavours were evaluated and a prototype formulation was tablets using mannitol with camphor: A subliming material. Int J Pharm
selected. This prototype formulation had Eudragit EPO 1997; 152: 127-131. http://dx.doi.org/10.1016/S0378-5173(97)04924-7
coated taste masked pellets and selected excipients. Its
disintegration time was found to be about 8 seconds. Tablets Cite this article as:
were evaluated for their taste, disintegration time, hardness, Kothapally Naresh Kumar, Devareddy Sandeep. Formulating taste-masked
orally disintegrating tablets of a bitter drug ibuprofen. Int. Res. J. Pharm.
friability, water uptake and drug release profile. It was 2013; 4(11):71-78 http://dx.doi.org/10.7897/2230-8407.041117
concluded from this study that water insoluble, water
permeable polymer system like Eudragit EPO can effectively

Source of support: Nil, Conflict of interest: None Declared

Page 78

View publication stats