Short Communication
AN APPROACH FOR TASTE MASKING OF BITTER DRUG
ATOMOXETINE HCl
Y. Deepthi Priya* 1, Y.A.Chowdary2, T.E.G.K.Murthy3.
1. Arya College of Pharmacy, Kandi, Sangareddy, Medak.
2. N.R.I College of Pharmacy, Pothavarappadu, Vijayawada.
3. Bapatla College of Pharmacy, Bapatla.
For correspondence* 1
Y. Deepthi priya,
Assistant professor,
Arya College of Pharmacy,
Kandi, Sangareddy, Medak.
Mobile no.09949027856.
E-mail: deepti_yarlagadda@yahoo.co.in
Although a variety of delivery systems are being developed for different routes of administration
like the oral, parenteral, nasal and transdermal, the oral route remains attractive for drug delivery
because of an easy, convenient, noninvasive and familiar method of drug delivery. The majority
of prescribed drugs are designed for oral application because of their self administration by the
patient. However, patients at the extremes of age, such as children and the elderly, often
experience difficulty in swallowing solid oral dosages forms. For these patients the drugs are
mostly provided in liquid dosage forms such as solutions, emulsions and suspensions. But these
dosage forms usually lead to perceptible exposure of the active drug ingredient to the taste buds,
which is a very serious problem when the drug has an extremely unpleasant or bitter taste. The
disagreeable taste of drugs causes difficulties in swallowing or causes patients to avoid their
medication thereby resulting in low compliance of patients1.
Hence, taste is an important factor in the development of dosage form and taste masking
becomes a pre-requisite for bitter drugs to improve the patient compliance especially in the
paediatric and geriatric population.
Various methods are available to mask the undesirable taste of drugs, some of which includes
addition of Sweeteners, Coating of drug particles, Ion Exchange resins, Microencapsulation and
Inclusion Complexes2.
Attention Deficit Hyperactivity Disorder (ADHD) is a neurobehavioral developmental disorder
primarily characterized by the co-existence of attentional problems and hyperactivity and
symptoms starting before seven years of age3. Atomoxetine HCl is a selective norepinephrine
reuptake inhibitor drug used in the treatment of Attention deficit hyperactivity disorder (ADHD)
in children and adolescents4. Atomoxetine HCl has an extremely caustic and bitter taste5. As the
drug has an extremely bitter taste, initial attempt was made to mask the bitter taste of the drug
there by improves the pediatric compliance.
Atomoxetine HCl, Mannitol, Sorbitol, Sucralose, Crosspovidone, Eudragit EPO co-polymer and
Magnesium stearate were procured from Aurobindo Pharma Ltd. as gift samples. All the other
ingredients were of analytical grade.
Atomoxetine HCl tablets were prepared by Direct compression using sweeteners for taste
masking, according to the formula given in table1. Atomoxetine HCl, Mannitol, Crosspovidone
XL were sifted through # 30 mesh and mixed for 10 min. Magnesium stearate was sifted through
# 40 mesh and lubricate the previous materials with magnesium stearate for 5 min and then
compressed in to tablets. Similarly, trials were done by changing the sweeteners with sorbitol,
Sucralose and a combination of sorbitol and Sucralose. A batch of 30 tablets was prepared for
different formulations.
Later, in line with the composition of F3, Atomoxetine HCl tablets were prepared using Wet
granulation technique employing water as a granulating agent and the composition details were
mentioned in Table 2.
Further, trails were taken to mask the bitter taste of Atomoxetine HCl with varying ratios of
drug: co-polymer as shown in the Table 3. In this method, polymeric solution was prepared by
dissolving Eudragit EPO in the solvent ethanol and followed by addition of Atomoxetine HCl.
Then the obtained drug- polymeric solution was subjected to gentle drying in order to evaporate
the solvent. The so obtained mixture was dried at 60°C and sifted through # 30 mesh and mixed
with optional excipients and compressed in to tablets.
For the prepared formulations, blend parameters were determined by Carr’s Index and Hausners
Ratio. Hardness of the tablets was determined by Monsanto hardness tester and Disintegration
time was determined by disintegration apparatus.
Initially several trails were carried out for taste masking of Atomoxetine HCl, using different
sweeteners such as Mannitol, Sorbitol and Sucralose either alone or in combination. These
resulted blends were compressed to tablets by direct compression technique. By tasting the
prepared tablets it was observed that bitter taste of Atomoxetine HCl was not masked. This is
because of the reason that, in direct compression technique drug particle is in the form of
physical mixture with the sweeteners and doesn’t form a coat around the drug particle.
Hence further trails were carried out using wet granulation technique with a view that sweetner
gets soluble in the solvent and get coated over the drug particle there by masking the bitter taste.
When the prepared tablets were evaluated for taste, it was observed that bitter taste was slightly
masked compared with the tablets prepared by direct compression.
All the formulations prepared by direct compression and wet granulation techniques were found
to show good flow properties and the tablets were also evaluated for weight variation, hardness
and disintegration time and the results were given in Table 4. In the present study, much
attention was not focused on disintegration time as taste masking was the primary criteria.
Reduction in Disintegration time is possible with increased concentration of disintegrants.
As taste masking was not achieved with the addition of sweeteners, further studies were carried
out by coating the drug particles with copolymer in the ratios of 1:0.25 and 1:0.5. With this
technique, taste masking was observed to a considerable extent but not completely. So, further
trials were planned to change the drug to copolymer ratio.
From the above results, it was concluded that taste masking with addition of sweeteners was not
achieved by direct compression and wet granulation processes. Even after coating the drug
particles with copolymer in the ratio of 1:0.5, complete taste masking was not attained. So,
further trials have to be carried out by changing the drug to copolymer ratio and also using other
taste masking techniques.
ACKNOWLEDGEMENTS
The authors are thankful to Aurobindo Pharma Ltd, Hyderabad for providing the gift samples
and the institution for providing the facilities to carryout the research work.
REFERENCES
1.
Kulkarni, Mohan Gopalkrishna and Menjoge, Anupa Ramesh. Taste masked
pharmaceutical compositions comprising bitter drug and pH sensitive polymer. WIPO
Patent Application. WO/2005/055987, 2005.
2.
Shalini sharma and Shaila lewis., Taste masking technologies: A review. International
Journal of Pharmacy and Pharmaceutical Sciences 2010; Vol 2, Issue 2, 6-13.
3.
Biederman J . Attention-deficit/hyperactivity disorder: a life-span perspective. J Clin
Psychiatry 1998; 59 Suppl 7: 4–16.
4.
Kratochvil CJ, Vaughan BS, Harrington MJ, Burke WJ. Atomoxetine: A selective
noradrenaline reuptake inhibitor for the treatment of attention- deficit/
hyperactivity
disorder. Expert Opin Pharmacother 2003; 4(7): 1165 -1174.
5.
Venkatesh, Gopi M, Harmon, Troy M and Taylor, John. Orally disintegrating tablets
of Atomoxetine. US Patent No. US 2006/0057199 A1, 2006.
TABLES
Table 1: Composition of Atomoxetine HCl tablets using direct compression
Ingredients(mg/tablet)
Atomoxetine HCl
Mannitol
Sorbitol
Sucralose
Crospovidone
Magnesium Stearate
Tablet Weight (mg)
F1
40.00
249.50
--6.00
4.50
300.00
F2
40.00
-249.50
-6.00
4.50
300.00
F3
40.00
-237.50
6.00
12.00
4.50
300.00
Table 2: Composition of Atomoxetine HCl tablets using Wet granulation
Ingredients(mg/tablet)
Atomoxetine HCl
Mannitol
Sorbitol
Sucralose
Crospovidone
Magnesium Stearate
Tablet Weight (mg)
F4
40.00
-237.50
6.00
12.00
4.50
300.00
Table 3: Composition of various drug: co-polymer ratios
S. No
1.
2.
Drug : Polymer ratio
1.0: 0.25
1.0: 0.5
Table 4: Blend and compressed parameters of various formulations
Formulation
F1
F2
F3
F4
Blend Parameters
Carrs Index (%)
18.29
19.58
18.62
17.22
Hausners Ratio
1.224
1.230
1.231
1.18
Compression Parameters
Avg. Wt (mg)
300.80
2
Hardness (kg/cm )
Disintegrating Time
4-6
3 min 45 sec
301.20
300.25
301.8
4-6
3 min 30 sec
4-6
4 min
4-6
3 min