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Abstract
This work investigates the complete bitter-taste-masking of primaquine phosphate (PRM) using a
solid dispersion with mono ammonium glycyrrhyzinate pentahydrate (GLY). This work also describes
the preparation of rapidly disintegrating tablets (RDTs) of PRM by a direct compression method using
superdisintegrant, croscarmellose sodium. A solid dispersion was prepared by the solvent
evaporation method. Fourier transform infrared spectroscopy (FTIR) and differential scanning
calorimetry (DSC) were performed to identify the physicochemical interaction between drug and
carrier, hence its effect on dissolution. In-vitro drug release studies were performed for RDTs at both
pH 1.2 and 6.8. Bitterness score was evaluated using a human gustatory sensation test. FTIR
spectroscopy and DSC showed no interaction of PRM in GLY solid dispersion. RDTs prepared from
solid dispersion showed complete bitter-taste-masking of PRM. RDTs containing solid dispersion
exhibited a better dissolution profile, at both pH 1.2 and 6.8, than pure PRM. Thus, the solid
dispersion technique can be successfully used for complete bitter taste masking of PRM.
Introduction
Correspondence: P. P. Shah,
Center of Relevance and
Excellence in NDDS, Pharmacy
Department, G H Patel building,
Donors Plaza, The M. S. University
of Baroda, Fatehgunj, Vadodara,
Gujarat, India, 390 002.
E-mail: punitpshah@gmail.com
Acknowledgements and funding:
The authors are thankful to Ajanta
Pharma Ltd, Mumbai and Sami
Labs, Bangalore, for providing the
gift sample of artemether and
mono ammonium glycyrrhyzinate
pentahydrate, respectively.
Further, the support from STIC,
Cochin is greatly acknowledged.
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The solid dispersion of PRM and GLY in 1:0.5 and 1:1 molar
ratio was carried out using the solvent evaporation method.
An accurately weighed quantity of PRM (750 mg in 7 mL)
was dissolved in water. Previously dissolved GLY (207.4 mg
in 7 mL) in water was added with constant stirring on a
magnetic stirrer. The solid mass was dried to a constant
weight in a hot-air oven at 100C. The dried powder was
passed through sieve No. 44 (ASTM 45, 355 mm) and stored
in a desiccator (Tarsons Products Pvt. Ltd, Baroda, India)
until further evaluation.
The physical mixtures of PRM and GLY were prepared by
mixing individual components geometrically, which
had previously been sieved through sieve No. 44 (ASTM 45,
355 mm), together with a spatula.
Characterization of solid dispersions
Rapidly disintegrating tablets (RDTs) containing the equivalent of 13.16 mg of PRM (7.5 mg primaquine base) were
compressed on an 8-station single rotary tabletting press
(GMC, Mumbai, India) using a 6-mm round shaped flat
punch with break line by the direct compression technique
(Fu et al 2004).
Prepared RDTs were evaluated for hardness (Hardness
tester 5Y; Electrolab, Mumbai, India), friability (Friabilator
EF2; Electrolab, Mumbai, India), disintegration time (Disintegrating apparatus ED 2; Electrolab, Mumbai, India) and
weight variation. The bitterness score was evaluated using a
human gustatory sensation test.
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0.5
1
1.5
2
2.5a
3
3.5
20
19
1
14
12
2
3+
6
8
18
18
14
2
6
a
Threshold concentration of PRM = 2.5 mg mL-1. Rating: 0 = tasteless,
1 = slightly bitter, 2 = moderately bitter, 3 = strongly bitter, 3+ = very
strongly bitter.
(c)
Transmittance (%)
(b)
(a)
500
1000
1500
2000
2500
Wavenumber (cm21)
Figure 1 FT-IR spectra of PRM (a), GLY (b), physical mixture (c) and solid dispersion (d).
3000
3500
4000
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(c)
Exotherm
(b)
(a)
30
90
150
210
Temperature (C)
270
330
Figure 2 DSC curve of PRM (a), GLY (b), physical mixture (c) and solid dispersion (d).
Table 2 Formulation of RDTs
Drug/excipients
RDT61
RDT62
RDT63
RDT64
RDT65
RDT66
PRM (mg)
GLY (mg)
Solid dispersion equiv. to 13.16 mg PRM
Microcrystalline cellulose (Avicel PH 302) (mg)
Dibasic calcium phosphate (directly compressible) (mg)
Croscarmellose sodium (mg)
Crospovidone (mg)
Magnesium stearate (mg)
37.42
29.88
2.4
0.3
37.42
29.88
2.4
0.3
37.42
29.88
2.4
0.3
37.42
29.88
2.4
0.3
13.16
54.14
2.4
0.3
13.16
24.26
29.88
2.4
0.3
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RDT61
RDT62
RDT63
RDT64
RDT65
RDT66
70.21 1.28
4349
4.14.2
0.27 0.09
69.89 1.19
4752
4.14.2
0.29 0.12
70.35 0.87
3440
4.44.5
0.19 0.10
69.75 1.32
4451
4.24.3
0.31 0.13
70.43 0.69
3641
4.34.4
0.21 0.09
70.28 0.76
3642
4.34.4
0.21 0.11
120
100
80
RDT65 at pH 6.8
RDT66 at pH 6.8
RDT63 at pH 6.8
RDT65 at pH 1.2
RDT66 at pH 1.2
RDT63 at pH 1.2
60
40
20
0
0
10
20
30
40
Time (min)
50
60
70
Figure 3 Dissolution profile of RDTs prepared from PRM (RDT65), physical mixture (RDT66) and solid dispersion (RDT63).
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Mean difference
Significance
RDT63 vs RDT65
RDT63 vs RDT66
RDT65 vs RDT66
16.93
5.417
-11.52
6.492
2.077
4.415
Yes
No
Yes
Conclusion
Mean difference
Significance
RDT63 vs RDT65
RDT63 vs RDT66
RDT65 vs RDT66
0.85
0.6183
-0.2317
1.235
0.8984
0.3366
No
No
No
Pure PRM
Pure GLY
Physical mixture (PM)
Solid dispersion (SD)
RDT65
RDT66
RDT63
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18
2
5
15
16
3+
18
17
20
20
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