Research Article
Nema et al
103
TASTE MASKING IN SYRUP CONTAINING HERBAL BITTER DRUGS:
FORMULATION, STANDARDIZATION AND STABILITY STUDIES
Nema M. V.*, Nimbekar T. P., Wanjari B. E., Dongarwar A.S., Katolkar P.P.
Manoharbhai Patel Institute of Pharmacy (B. Pharm.), Kudwa, Gondia- 441 416 (MS) INDIA
E-mail of Corresponding author: [email protected]
Abstract
Taste masking of bitter drugs has been challenge to scientists as taste is an important
parameter governing patient compliance. Several oral pharmaceuticals, numerous food and
beverage products and bulking agents have unpleasant bitter taste. In order to ensure patient
compliance bitterness masking becomes essential. The desire of improving the palatability
has prompted the development of numerous formulations with improved performance and
acceptability. Several approaches namely sensory, barrier, chemical and complexation have
been tried to mask the unpleasant taste of formulation. The purpose of the present was to
evaluate the bitterness of the prepared syrup formulation by using human taste sensor.
Keywords: Taste masking, Human taste sensor, Bitterness, Complexation
Introduction
sensation and therefore, formulation of
Taste masking, a perceived reduction of an
foods, beverages and oral pharmaceuticals
undesirable taste that would otherwise
attempt
exist. The ideal solution to reduce or
perception.[3,4] Hence bitterness control has
inhibit bitterness is the discovery of a
become of commercial importance to a
universal inhibitor of all bitter tasting
pharmaceutical chemist.
substances that does not affect the other
Hence, masking the bitter taste of drugs is
taste modalities such as sweetness or
a potential tool for improvement of patient
saltiness, as bitterness, a taste modality
compliance, which in turn decides the
since the earliest
commercial success of the product.[5] To
days of recorded
to
alleviate
bitter
taste
civilization.[1,2] Evolution and adaptation
improve
of a sensitivity and negative hedonic
pharmaceutical product, many techniques
response to bitter taste of materials from
have been developed, which have not only
plant sources evolved mainly through
improved the taste of the product, but also
forgoing alkaloids found in many plants.
the stability of the drug in the formulation
Bitter taste is unpleasant to the human oral
and the overall performance of the
IJBAR (2011) 02(03) the
palatability
of
a
www.ijbar.ssjournals.com
Research Article
Nema et al
104
product.[6,7] The available technologies
Chemical, Mumbai. All other chemicals
effectively mask the objectionable bitter
were used as analytical grade.
taste
Preformulation
of
drugs
but
require
skillful
study:
The
overall
application without affecting delivery of
objective of preformulation testing is to
the drug. With application of these
generate
techniques and proper evaluation of taste
formulator
masking effect one can improve product
bioavailable dosage forms, which can be
preference to a large extent.[8] Moreover,
mass produced. Preformulation studies
the
masking
include studies of the physiochemical
methodology requires great technical skill,
properties of herbal extracts and an
and the need for massive experimentation.
assessment of their relevance to the final
We
formulation, the chemical and physical
development
have
of
taste
previously
reported
the
information
in
useful
developing
to
stable
the
&
quantitative evaluation of bitterness of
stability
various
chemical/physical compatibility of the
drug
formulations,
such
as
of the herbal extracts and
antibiotics and amino acid preparations,
active constitute with potential excipients.
etc. using a taste sensor.[9-11]
Preparation of syrup [12-13]
The goal of the present study, therefore
Preparation of extract solution: Extracts
was to minimize the bitter taste of a syrup
of Neem and Phyllanthus were weighed
prepared by using Neem and Phyllanthus
accurately and mixed separately with
extracts as both the herbs are well known
specified quantity of purified water and
for imparting bitter taste by using the
stirred thoroughly by using mechanical
human
stirrer.
taste
sensor
for
their
hepatoprotective activity.
Preparation of syrup base: Weighed
Materials and Methods:
accurate quantity of sucrose, purified
Materials: Neem extract powder (Sanat
Products
Co.,
Ltd.,
Sikanderabad
),
water, citric acid & allowed to boil at a
temperature about 1100C ± 20C over hot
(Natural
plate, until a clear light yellow syrupy
Remedies Pvt., Ltd., Bangalore) and the
liquid was formed and after the solution
other excipients like Glycerine, Sorbitol
comes to room temperature, Sodium
solution, Xanthum gum, Citric acid,
Citrate in purified water solution was
Sucrose
added and stirred continuously.
Phyllanthus
IP,
Extract
Powder
Methyl paraben,
Propyl
paraben, Sodium citrate, Propylene glycol,
Preparation of preservatives solution:[14]
etc were purchased from SD Fines
Combination of Methyl Paraben & Propyl
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
105
Paraben dissolved in propylene glycol as a
standard
cosolvent before addition to the syrup and
volumetric flask. Methanol was added and
the weighted quantity of other excipients
sonicated in ultrasonic water bath and the
was added and make up the required
resulting solution was used as a reference
volume with purified water shown in
solution for Phyllanthin and Rutin (Purity
Table-3.
87 % w/w and 95 %. w/w) respectively.
Preparation of Sample for HPTLC:
The solvent system for Phyllanthin: n-
HPTLC Instrument (Camag, Switzerland)
Hexane: Acetone: Ethyl acetate (74:12:8)
consists of TLC scanner III, Application
detected at 230 nm and for Rutin the
device Linomat V, Twin trough plate
solvent system: Ethyl acetate: Formic acid:
development chamber and Win CATS
G.A.A.: Water. (100: 11: 11: 26) detected
software was used. Silica gel 60F (254)
at 362 nm.
Pre-coated aluminum foil plate with
Stability studies: Stability study of the
thickness 0.2 mm was used.[15]
prepared syrup was carried out for three
Extract solution: The known amount of
months data. The syrup was kept at
Phyllanthus
was
different temperature and relative humidity
dissolved separately in 25 ml of methanol
as per ICH guidelines (25 0C & 60 % RH,
and sonicated in ultrasonic water bath and
300C & 65 %RH, 400C & 75 %RH). The
filtered through Whatmann filter paper
Physical Parameters like pH, taste, odour
(44). The resulting solution used as the
and other chemical parameters were
and
Neem
extracts
[16]
extract solution.
Test
solution
(Syrup):
The
known
(100:100:100 ml) with extraction media
n-Butanol:
Methanol,
25:3:1). Further concentrated to dryness in
Buchi’s rotavapor and make up to 25 ml
with
methanol
and
filtered
through
Whatmann filter paper (44). The resulting
solution was used as the test solution.
Preparation of the reference standard
solution
transferred
to
25
ml
checked on the weekly basis.
amount of Syrup was extracted thrice
(Chloroform:
and
(Phyllanthin
and
Rutin):
Results and Discussion:
An
acceptable
syrup
formulation
containing Phyllanthus and Neem extracts
as active bitter principles was developed
by modifying the taste of final preparation
using citric acid, xanthan gum, sodium
chloride, masking agent, and flavours like
Honey, Orange, Melon. Finally, sensory
evaluations of ten expert tasters have
shown that Honey flavour was the best
among these three flavours.[17-22]
Accurately weighed Phyllanthin (2.529
mg) & Rutin (2.891 mg) as a reference
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
106
Conclusion:
for oral pharmaceuticals. Indian J.
In the present study attempt has been made
Pharm. Sci. 2002; 64 (1):10–17.
to minimize the bitter taste of a syrup
2. Beinz Martin, Taste masking strategies
prepared using Neem and Phyllanthus
for drug dosage forms. Manufacturing
extracts. It is possible to prepare taste
Chemist 1996; 18-20.
masked syrup formulation with improved
3. Pandya E, Harish B, Thomas P. Taste
palatability by using Citric acid, Sodium
Masking
for
Unpalatable
citrate, Xanthum gum, Sodium chloride,
Formulations. US Patent 1998; 837(5):
Sodium saccharine, Masking agent, and
286.
Flavours like Honey, Orange and Melon.
4. Popescu
MC, Mertz
ET. Taste
Finally, sensory evaluations of ten expert
Moderating Pharmaceutical. US Patent
tasters have shown that Honey flavour was
1991:5(9): 819.
the best among these three flavours. The
5. Katsuragi Y, Kurihara K. Specific
optimized syrup formulation during this
inhibitor
experiment
1993;365:213-214.
was
quite
acceptable
in
comparison to the syrup prepared without
for
bitter
taste.
Nature
6. Chandrashekar J, Mueller KL, Hoon
taste masking efforts.
MA, Adler E, Feng L, Guo W, Zuker
Acknowledgement:
CS, Rybat JP, et al. T2Rs function as
Authors are thankful to Sanat Product Co.
Ltd.(Sikanderabad
A.P.)
and
Natural
Remedies Pvt. Ltd. (Bangalore K.A.) for
providing the gift samples of extract.
Authors are greatful to Shri. Rajendra Jain,
Secretory, Gondia Education Society, for
providing necessary facilities for the
research work in Manoharbhai Patel
Institute of ‘B’
Pharmacy, Kudwa,
Gondia.
References:
1. Nanda A, Kandarapu R, Garg S. An
update on taste masking technologies
bitter taste receptors. 2000; 100:703–
711.
7. Cano J,
Mintijano H,
Lopez-
Cremades F, Borrego F, Masking of
the bitter taste of pharmaceuticals.
Manuf. Chemist 2000;71:16–17.
8. Fuisz,
Richard C, Taste masked
medicated pharmaceutical. US Patent
1991; 5(28): 632.
9. Agarwal R, Mittal R, Singh A, Studies
of ion-exchange resin complex of
chloroquine
phosphate,
Drug
Development. Ind. Pharm. 2000; 26
(7):773–776.
10. Friend DR,
Polyacrylate
resin
microcapsules for taste masking of
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
11. antibiotics. J. Microencap. 1992;9(4):
469–480.
107
drug delivery system’. 1999; Sixth
edition: 240-246.
12. Miyanaga Y, Kobayashi Y, Ikezaki H,
19. Cano J,
Mintijano H,
Lopez-
Uchida T. Sensors and materials
Cremades F, Borrego F. Masking of
2002;14: 455-465.
the bitter taste of pharmaceuticals,
13. Quality control for India’s herbal
drugs
(online).
2007.
(http://www.SciDev.NetHome)
14. Sirops FR, Cod Sirupi PG, Sirupe G.
Soiroppi IT, Jarabe SP. Syrups. The
Manuf. Chemist 2000; (71):16–17.
20. Hiremath JG, Shastry CS, Srinath MS.
Pharmaceutical approaches of taste
masking in oral dosage forms. Indian
Drugs 2004; 41(5):253-257.
Dispensatory1926.
21. Keast SJ, Breslin P, Beauchamp GK.
Compiled and Edited by Ivor Hughes.
Suppression of bitterness using sodium
(http://www.herbdatanz. Com /syrups
salts. Chimia 2001; 55: 441–447.
United
States
22. Lienhop KS, et al. Taste masked liquid
_usd_1926.htm)
15. Khanfar
M,
Khalil
R,
Abujafal.
Evaluation of preserving efficacy for
different cough syrups manufactured
pharmaceutical delivery system, US
Patent 1998; 51: 730-997.
23. Niazi S. and Shemesh A. Chewing
pharmaceutical
Gum Containing a Medicament and
companies. Int. J. of Pharmacology
Taste Maskers. US Patent 1987; 04:
2009; 5(5): 319-322.
639-368.
by
different
16. Jeganathan NS, Kannan K., Manavalan
R, Hannah RV., Standardization of a
Siddha
Formulation
Amukkara
Curanam by HPTLC. African Journal
of Traditional. Complimentary and
Alternative Medicines 2008; 5(2): 131140.
17. Sethi PD, High Performance Thin
Layer Chromatography. 1st Edition,
CBS Publishers and Distributors, New
Delhi, India 1996; 3-71.
18. Ansel C, Nichclas G. Text book of
‘Pharmaceuticals dosage forms and
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
108
Figure 3:- Selection and optimization of
salts concentration
Figure 1: Optimization of sugar
quantity & process
6
5
4
Scores
5
scores
4
3
3
2
2
1
1
0
A
0
A
B
C
D
B
C
D
E
F
Syrup
E
Syrup
A – Without salt,
A – Invert syrup base (Readymade),
B -Sodium chloride 0.5%, 1%, 1.5%, 2%,
B – Sugar without agitation,
C -Pottasium chloride 1.0%, 2%,
C – 60% Sugar syrup (acid hydrolyzed),
D -Ammoniun chloride 1.0%, 2%,
D - 75% Sugar syrup (acid hydrolyzed),
E -Sodium bicarbonate 1.0%, 2%,
E - 90% Sugar syrup (acid hydrolyzed).
F - Glycine 0.5%.
Figure 2: Selection and optimization of
Acids/Buffering agents
Figure 4:- Selection and optimization
of viscosity modifiers
6
7
5
6
Scores
4
scores
5
4
3
2
3
2
1
1
0
A
0
A
B
C
D
E
F
B
G
C
D
E
F
Syrup
Syrup
A– Without acid/buffering agent,
B– Citric acid 2% and Sodium citrate 2%,
C – C. acid 1.5%, and Sod. citrate 0.5%,
D – C. acid 1.0% and Sod. citrate 1%,
E- C. acid 0.5% and Sod. citrate 1.0%,
F-
Fumaric acid 0.3% and Sod. citrate
A –Without viscosity modifier,
B - Xantham gum 0.1%, 0.2%,0.3%,
C - Veegum 0.2%,
D - H.P.M.C. 0.2%,
E - P.V.P. 0.2%,
F - Carbapol 0.2%.
0.5%,
G- Mallic acid 0.5% and Sod. citrate 1.0%.
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
Figure 5:- Selection and optimization of
Artificial sweetners
109
Figure 7:- Selection and optimization of
Flavouring agent:
6
5
7
4
Scores
6
Scores
5
3
4
2
3
1
2
0
A
B
C
D
1
E
F
G
H
Syrup
0
A
B
C
D
E
F
G
A – Without artificial sweetener,
Syrup
A -Without artificial sweetener,
B - Sodium Saccharine 1mg/ml & 2mg/ml,
B - Sodium Saccharine 1mg/ml & 2mg/ml,
C- Stevioside 1mg/ml & 2mg/ml,
C- Stevioside 1mg/ml & 2mg/ml,
D - Sucralose 1mg/ml & 2mg/ml,
D - Sucralose 1mg/ml & 2mg/ml,
E - Acelfame –K 1mg/ml & 2mg/ml,
E - Acelfame –K 1mg/ml & 2mg/ml,
F- Glycerrhinate Ammonium salt 1mg/ml
F- Glycerrhinate Ammonium salt 1mg/ml
& 2mg/ml,
& 2mg/ml,
G -Aspartame 1mg/ml & 2mg/ml.
G -Aspartame 1mg/ml & 2mg/ml.
Figure 6: Selection and optimization of
Figure 8:- Comparative evaluation of
flavouring agents:
masking agent
4
5
3.5
3
2.5
Scores
scores
4.5
4
3.5
3
2.5
2
2
1.5
1
1.5
1
0.5
0
A
0.5
0
B
C
Syrup
A
B
C
D
E
Syrup
A –Without masking agent,
A
B -Masking Flavour (0.3%v/v) Symrise,
substance,
C –Bitterness Modifier (0.5%) IFF,
B - Masking agent (0.3%v/v) & Melon
D – Mask cool (0.5%) Symrise,
E –Masking Flavour (0.5%v/v) IFF.
-
Without
masking
&
flavoring
flavour (0.1%v/v),
C - Masking agent (0.3%v/v) & Orange
flavour (0.1%v/v),
D - Masking agent (0.3%v/v) & Honey
flavour (0.1%v/v).
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
D
Research Article
Nema et al
110
Table 1: Compatibility studies of Neem Extract (B.No.- 125086)
S.N.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Sample
Neem Ext.+ Purified Water
Neem Ext + Methyl paraben+ Water
Neem Ext + Propyl paraben+ Water
Neem Ext +Methyl paraben+ Propyl paraben +
Water
Neem Ext + Methyl paraben + Propyl paraben +
Sorbitol + Water
Neem Ext + Methyl paraben+ Propyl paraben +
Propylene glycol + Water
Neem Ext + Methyl paraben+ Propyl paraben +
Glycerin + Water
Neem Ext + Methyl paraben + Propyl paraben +
Sodium chloride + Water
Neem Ext + Methyl paraben + Propyl paraben +
Honey flavour+ Water
Neem Ext + Methyl paraben + Propyl paraben +
Sod. Saccharin+ Water
Neem Ext + Methyl paraben + Propyl paraben +
Citric acid + Water
Neem Ext + Phyllanthus Ext + Water
Drug Excipient Ratio
Initial
Observations400 C
1 wk 2 wk 3 wk 4 wk
NC NC NC NC
NC NC NC NC
NC NC NC NC
NC NC NC NC
1:100
1: 0.18: 100
1: 0.02: 100
1: 0.18: 0.02: 100
Clear Solution
Clear Solution
Clear Solution
Clear Solution
1: 0.18: 0.02: 5 :100
Clear Solution NC
NC
NC
NC
1: 0.18: 0.02: 1: 100
Clear Solution NC
NC
NC
NC
1: 0.18: 0.02: 5:100
Clear Solution NC
NC
NC
NC
1: 0.18: 0.02: 1: 100
Clear Solution NC
NC
NC
NC
1: 0.18: 0.02: 0.5:100
Clear Solution NC
NC
NC
NC
1: 0.18: 0.02: 2 : 100
Clear Solution NC
NC
NC
NC
1: 0.18: 0.02: 0.5 : 100
Clear Solution NC
NC
NC
NC
1: 0.5 : 100
Clear Solution NC
NC
NC
NC
NC – No change in description
PM – Particulate matter
Table 2: Compatibility studies of Phyllanthus Extract (B.No. PA/04004)
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Sample
Phyllanthus Ext.+ Purified Water
Phyllanthus Ext.+ Methyl paraben+ Water
Phyllanthus Ext.+ Propyl paraben+ Water
Phyllanthus Ext +Methyl paraben+ Propyl
paraben+ Water
Phyllanthus Ext + Methyl paraben + Propyl
paraben + Sorbitol + Water
Phyllanthus Ext + Methyl paraben+ Propyl
paraben + Propylene glycol + Water
Phyllanthus Ext + Methyl paraben+ Propyl
paraben + Glycerin + Water
Phyllanthus Ext + Methyl paraben + Propyl
paraben + Sodium chloride + Water
Phyllanthus Ext + Methyl paraben + Propyl
paraben + Honey flavour + Water
Phyllanthus Ext + Methyl paraben + Propyl
paraben + Sod. saccharin+ Water
Phyllanthus Ext + Methyl paraben + Propyl
paraben + Citric acid + Water
Drug: Excipient
Ratio
Initial
Observations 400 C
0. 5: 100
0. 5: 0.18: 100
0. 5 :0.02:100
0. 5: 0.18: 0.02: 100
Clear Solution
Clear Solution
Clear Solution
Clear Solution
1 wk
NC
NC
NC
NC
2 wk
NC
NC
NC
NC
3 wk
NC
NC
NC
NC
4 wk
NC
NC
NC
NC
0. 5: 0.18: 0.02: 5:100
Clear Solution NC
NC
NC
NC
0. 5:0.18: 0.02 :1:100
Clear Solution NC
NC
NC
NC
0. 5: 0.18:0.02 :5: 100
Clear Solution NC
NC
NC
NC
0. 5: 0.18: 0.02: 1: 100
Clear Solution NC
NC
NC
NC
0. 5: 0.18: 0.02: 0.5:100 Clear Solution NC
NC
NC
NC
0.25: 0.18: 0.02: 2:100
Clear Solution NC
NC
NC
NC
0. 5: 0.18: 0.02: 0.5 :
100
Clear Solution NC
NC
NC
NC
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
111
NC – No change in description
PM – Particulate matter
Table 3: In-process observation of syrup
Sr.No
.
1.
Parameters
Purified Water
Extract solution
Final syrup
pH
6.40
5.24
4.02
2.
Description
Clear
Hazy
Brown syrupy liquid
Table 4: Optimization of sugar quantity and process
Syrup
base
Parameters
Bitterness
Aftertaste
Mouth feel
Sweetness
A
Moderate
Strong
OK
B
Moderate
Strong
C
D
E
Moderate
Moderate
Mild
Moderate
Moderate
Mild
Scores
Moderate
Overall
acceptability
No
OK
Moderate
No
2
OK
OK
OK
Moderate
Moderate
Strong
No
No
Yes
3
4
5
1
A – Invert syrup base (Readymade), B – Sugar without agitation, C – 60% Sugar syrup
(acid hydrolyzed), D - 75% Sugar syrup (acid hydrolyzed), E - 90% Sugar syrup (acid
hydrolyzed).
Inference: Taste evaluation of samples under evaluation containing 90 % w/v sugar was
better tasting than the remaining samples were shown in Table-4 and Figure-1.
Table 5: Selection and optimization of Acids/Buffering agents
Six samples have been prepared and evaluated for the following parameters.
Syrup
Base
A
B
C
D
E
F
G
Bitterness
Moderate
Moderate
Moderate
Moderate
Mild
Moderate
Moderate
Aftertaste
Moderate
Moderate
Moderate
Moderate
Mild
Moderate
Moderate
Parameters
Mouthfeel
Sweetness
OK
OK
OK
OK
OK
OK
OK
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Overall
acceptability
NO
NO
NO
NO
YES
NO
NO
Scores
7
5
4
2
1
3
6
A– Without acid/buffering agent, B– Citric acid 2% and Sodium citrate 2%, C – C. acid
1.5%, and Sod. citrate 0.5%, D – C. acid 1.0% and Sod. citrate 1%, E- C. acid 0.5% and Sod.
citrate 1.0%, F- Fumaric acid 0.3% and Sod. citrate 0.5%, G- Mallic acid 0.5% and Sod.
citrate 1.0%.
Inference: Taste evaluation of samples under evaluation containing Citric acid 0.5 % &
Sodium citrate 1.0 % was better tasting than the remaining samples were shown in Table-5
and Figure-2.
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
112
Table 6: Selection and optimization of salts concentration
Five samples have been prepared and evaluated for the following parameters
Syrup
Base
Parameters
Bitterness
Aftertaste
Mouthfeel
Sweetness
A
B
C
D
E
F
Moderate
Mild
Moderate
Moderate
Moderate
Moderate
Moderate
Mild
Moderate
Moderate
Moderate
Moderate
OK
OK
OK
OK
OK
OK
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Overall
acceptability
NO
YES
NO
NO
NO
NO
Scores
1
6
4
5
2
3
A – Without salt, B -Sodium chloride 0.5%, 1%, 1.5%, 2%, C -Pottasium chloride 1.0%, 2%,
D -Ammoniun chloride 1.0%, 2%, E -Sodium bicarbonate 1.0%, 2%, F - Glycine 0.5%.
Inference: Taste evaluation of samples under evaluation containing Sodium chloride 1.0 %
was better tasting than the remaining samples were shown in Table-6 and Figure-3.
Table 7: Selection and optimization of viscosity modifiers
Five samples have been prepared and evaluated for the following parameters
Parameters
Syrup
Base
Bitterness
Aftertaste
Mouthfeel
Sweetness
A
B
C
D
E
F
Moderate
Mild
Moderate
Moderate
Moderate
Moderate
Moderate
Mild
Moderate
Moderate
Moderate
Moderate
OK
OK
OK
OK
OK
OK
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Overall
Acceptability
NO
YES
NO
NO
NO
NO
Scores
1
6
4
5
2
3
A –Without viscosity modifier, B - Xantham gum 0.1%, 0.2%,0.3%, C - Veegum 0.2%,
D - H.P.M.C. 0.2%, E - P.V.P. 0.2%, F - Carbapol 0.2%.
Inference: Taste evaluation of samples under evaluation containing Xanthum gum 0.1 % was
better tasting than the remaining samples were shown in Table-7 and Figure-4.
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
113
Table 8: Selection and optimization of artificial sweetners.
Six samples have been prepared and evaluated for the following parameters.
Syrup
Base
Bitterness
Aftertaste
A
B
C
D
E
F
G
Moderate
Mild
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Mild
Moderate
Moderate
Moderate
Moderate
Moderate
Parameters
Mouthfeel
Sweetness
OK
OK
OK
OK
OK
OK
OK
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Overall
Acceptability
NO
YES
NO
NO
NO
NO
NO
Scores
1
7
5
6
4
2
3
A – Without artificial sweetener, B - Sodium Saccharine 1mg/ml & 2mg/ml, C- Stevioside
1mg/ml & 2mg/ml, D - Sucralose 1mg/ml & 2mg/ml, E - Acelfame –K 1mg/ml & 2mg/ml,
F- Glycerrhinate Ammonium salt 1mg/ml & 2mg/ml, G -Aspartame 1mg/ml & 2mg/ml.
Inference: : Taste evaluation of samples under evaluation containing Sodium Saccharine 2
mg/ml was better tasting than the remaining samples were shown in Table-8 and Figure-5.
Table 9: Selection and optimization of masking agent
Five samples have been prepared and evaluated for the following parameters
Syrup
Base
Bitterness
Aftertaste
A
B
C
D
E
Moderate
NO
Moderate
Moderate
Moderate
Moderate
Mild
Moderate
Moderate
Moderate
Parameters
Mouthfeel
Sweetness
OK
OK
OK
OK
OK
Moderate
Moderate
Moderate
Moderate
Moderate
Overall
acceptability
NO
YES
NO
NO
NO
Scores
1
5
2
3
4
A –Without masking agent, B -Masking Flavour (0.3%v/v) Symrise, C –Bitterness Modifier
(0.5%) IFF, D – Mask cool (0.5%) Symrise, E –Masking Flavour (0.5%v/v) IFF.
Inference: Taste evaluation of samples under evaluation containing Masking flavour (0.3 %)
from Symrise was better tasting than the remaining samples were shown in Table-9 and
Figure-6.
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
114
Table 10: Selection and optimization of flavouring agent:
Eight samples have been prepared and evaluated for the following parameters.
Syrup
Base
A
B
C
D
E
F
G
H
Parameters
Bitterness
Moderate
Mild
NO
NO
Mild
NO
Mild
Mild
Aftertaste
Mouthfeel
Sweetness
Moderate
Moderate
Mild
Mild
Moderate
Mild
Moderate
Moderate
OK
OK
OK
OK
OK
OK
OK
OK
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Overall
acceptability
NO
NO
YES
YES
NO
YES
NO
NO
Scores
1
3
6
6
2
6
4
5
A – Without flavoring substance, B -Masking agent (0.3%v/v) & Banana flavour (0.1%v/v)
C -Masking agent (0.3%v/v) &Orange flavour (0.1%v/v), D - Masking agent (0.3%v/v) &
Honey flavour (0.1%v/v),E -Masking agent (0.3%v/v) & Lemon flavour (0.1%v/v), F Masking agent (0.3%v/v) &Melon flavour (0.1%v/v),G -Masking agent (0.3%v/v) & Mango
flavour (0.1%v/v), H - Masking agent (0.3%v/v) & Vanilla flavour (0.1%v/v).
Inference: Taste evaluation of samples under evaluation containing Masking flavour (0.3
%v/v) and of flavouring agents (0.1 % v/v) Melon, Orange, Honey flavours was better tasting
than the remaining samples.
Table 11: Comparative evaluation of flavouring agents:
Syrup
Base
A
B
C
D
Bitterness
Moderate
Mild
Mild
NO
Aftertaste
Moderate
Mild
Moderate
NO
Parameters
Mouthfeel
Sweetness
OK
OK
OK
OK
Moderate
Moderate
Moderate
Moderate
Overall
acceptability
NO
NO
NO
YES
Scores
1
2
3
4
A - Without masking & flavoring substance, B - Masking agent (0.3%v/v) & Melon flavour
(0.1%v/v), C - Masking agent (0.3%v/v) & Orange flavour (0.1%v/v),D - Masking agent
(0.3%v/v) & Honey flavour (0.1%v/v).
Inference: 40 % of the participants preferred Honey flavour over other three samples under
evaluation were shown in Table-11 and Figure-8.
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
115
Table 10: Quantification of Neem extract in syrup formulation with respect to marker
compound by HPTLC:
S.No.
Samples
1.
2.
3.
4.
5.
6.
7.
8.
Neem-Extract
Syrup Control
Syrup 1M, 400C
Syrup 2M, 400C
Syrup 3M, 400C
Syrup 3M, 250C
Neem-Extract 3M, 40o
Rutin standard
Application
Volume
10 µl
25 µl
25 µl
25 µl
15 µl
15 µl
10 µl
10 µl
Sample Preparation
(mg/ml)
249.8/25
30124/25
28305/25
27160/25
28220/25
26530/25
246.3/25
0.0092512
Peak area
9685.5
2894.5
2705.7
2726.5
1825.5
2118.5
8001.2
12820.2
Rutin content
% w/w
0.0608
0.0603
0.0601
0.0689
0.0585
0.0600
0.0509
--------
Table 11: Quantification of Phyllanthus extract in syrup formulation with respect to
marker compound by HPTLC:
S.No
Samples
Application
Volume
Sample Preparation
(mg /ml)
Peak area
1.
Phyllanthus-Extract
15 µl
505.6/25
1098.9
Phyllanthin
content
% w/w
0.0119
2.
3.
4.
5.
6.
Syrup Control
Syrup 1M, 400C
Syrup 2M, 400C
Syrup 3M, 400C
Syrup 3M, 250C
10 µl
10 µl
10 µl
10 µl
10 µl
30124/25
28305/25
27160/25
28220/25
26530/25
3889.4
3983.8
4007.9
3804.9
3968.7
0.0106
0.0115
0.0121
0.0110
0.0123
7.
Phyllanthus-Extract 3M, 400C
15 µl
501.6/25
1174.1
0.0131
7 µl
2.529/10
5097.0
----------
8.
Phyllanthin standard
IJBAR (2011) 02(03) www.ijbar.ssjournals.com
Research Article
Nema et al
116
Table12: Accelerated Stability Studies
Storage condition/
sampling interval
Specification
Accelerated Stability Data (ICH ZONE: I, II, III & IV)
Description
pH
Wt/ml
(gm/cc)
Brown coloured syrup with
3.5-4.5
1.11- 1.16
characteristic taste of Honey flavour.
Assay (HPTLC)
Initial
Brown coloured syrupy with
characteristic taste of Honey flavour.
3.98
1.1432
Phyllanthin
Content
% w/w
0.0106
Rutin
Content
% w/w
0.0603
1 Month @ 40°C
& 75% RH
Brown coloured syrupy with
characteristic taste of Honey flavour.
4.01
1.1544
0.0115
0.0601
2 Months @ 40°C
& 75% RH
3 Months @ 40°C
& 75% RH
Brown coloured syrupy with
characteristic taste of Honey flavour.
Brown coloured syrupy with
characteristic taste of Honey flavour.
4.02
1.1231
0.0121
0.0689
4.04
1.1318
0.0110
0.0585
Table 13: Real Time Stability Studies
Storage condition/
sampling interval
Real Time Stability Data (ICH ZONE: I & II)
Description
pH
Wt/ml
(gm/cc)
Assay (HPTLC)
Specification
Brown coloured syrupy liquid
characteristic taste of Honey flavour.
3.5-4.5
1.11- 1.16
Phyllanthin
Content
% w/w
Rutin
Content
% w/w
a) Initial
Brown coloured syrupy liquid
Characteristic taste of Honey flavour.
3.98
1.1432
0.0106
0.0603
b) 3 Months @ 25°C
& 60 % RH
Brown coloured syrupy liquid
Characteristic taste of Honey flavour.
4.00
1.1420
0.0123
0.0600
IJBAR (2011) 02(03) www.ijbar.ssjournals.com