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INFORMATION
Abstract
In the present study, the performance of PROSOLV® EASYtab SP
was tested in four DC formulations with different model APIs.
Each of the selected APIs presented a particular challenge in terms
of producing tablets with suitable hardness, weight uniformity,
content uniformity and/or reliable dissolution profiles. PROSOLV®
EASYtab SP was shown to perform considerably better than the
corresponding physical mixture of its components for all formu-
lations tested.
1 mm
Introduction
PROSOLV® EASYtab SP is a ready-to-use tablet excipient composite, In each case, the functional performance of the PROSOLV ®
comprised of microcrystalline cellulose as filler/binder, colloidal EASYtab SP formulations were compared to simple dry blends
silicon dioxide as flow aid, sodium starch glycolate as disintegrant of the individual components.
and sodium stearyl fumarate as lubricant. PROSOLV® EASYtab SP
is specifically designed for use in direct compression. Parameters measured in this study were: Compaction force, ejec-
In direct compression formulations, the active ingredient can of- tion force, tablet disintegration time, content and weight uniformity
ten present challenges in terms of achieving powder blends with as well as API dissolution. PROSOLV ® EASYtab SP formulations
decent flowability, compactability and homogeneity. These problems were simply blended with the API for 18 minutes. For the physical
can cause insufficient tablet hardness, poor weight and/or content blends, the API was blended with microcrystalline cellulose, sodium
uniformity and inconsistent drug release. The impact of adverse starch glycolate, and silicon dioxide for 15 minutes. Sodium stearyl
API properties grows with increasing concentration in the formu- fumarate was then added and blended for an additional three
lation. For the purpose of this study, four medium-dose formula- minutes.
tions of APIs were selected, each of which presented its individual
morphological challenge. (See overview in Table 1)
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TECHNICAL
INFORMATION
450
7
Formulation 1 with PROSOLV ® EASYtab SP Formulation 1 with PROSOLV ® EASYtab SP
400
Tensile Strength [MPa]
6 Formulation 2 with the Dry Blend Formulation 2 with the Dry Blend
Disintegration Time [s]
350
5
300
greater shorter
4 hardness 250 disintegration
time
200
3
150
2
100
1 50
0 0
0 1 2 3 4 5 6 7 8 9 10 11 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50
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500 100
90
450
less
friction
70
400
60
50
350
40
30
300
Formulation 1 with PROSOLV EASYtab SP
®
20
Formulation 1 with PROSOLV ® EASYtab SP
Formulation 2 with the Dry Blend 10
Formulation 2 with the Dry Blend
250
0
1 2 4 5 6 8 10 0 15 30 45 60 75 90 105 120 135 150 165
200 0 3 7 9 11
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TECHNICAL
INFORMATION
8 450
400
7
greater
Disintegration Time [s]
hardness 350
Tensile Strength [MPa]
6
300
5 shorter
250
disintegration time
4
200
3
150
2 100
1 3
Formulation 1 with PROSOLV ® EASYtab SP 50
Formulation 1 with PROSOLV ® EASYtab SP
Formulation 2 with the Dry Blend Formulation 2 with the Dry Blend
0 0
0 1 2 4 5 6 7 8 9 10 11 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50
Compression Force [kN] Tensile Strength [MPa]
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100
500
90
450 80
less 70
friction
400
60
50
350
40
300 Formulation 1 with PROSOLV ® EASYtab SP 30
Formulation 2 with the Dry Blend 20
250 Formulation 1 with PROSOLV ® EASYtab SP
10 Formulation 2 with the Dry Blend
200 0
0 1 2 3 4 5 6 7 8 9 10 0 15 30 45 60 75 90 105 120 135 150 165
20 % lower ejection forces; especially at high compression forces Equivalent dissolution times. Dissolution test –
pass USP-NLT 75 % in 45 min (100 % in 5 min).
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TECHNICAL
INFORMATION
shorter
Tensile Strength [MPa]
3.50
hardness disintegration time
160
3.00 140
2.50 120
100
2.00
80
1.50
60
1.00
40
0.50 20
0.00 0
0 1 2 3 4 5 6 7 8 9 10 11 12 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00
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390 100
380
less 90
370 friction 80
360
70
350
60
340
50
330
40
320
310 30
300 20
Formulation 1 with PROSOLV ® EASYtab SP Formulation 1 with PROSOLV ® EASYtab SP
290 10
Formulation 2 with the Dry Blend Formulation 2 with the Dry Blend
280 0
0 1 2 3 4 5 6 7 8 9 10 0 15 30 45 60 75 90 105 120 135 150 165
API Content Uniformity 0.74 % 7.93 % • 10 – 15 % lower ejection forces (Figure 10)
Tab. 7 Atenolol – Formulation Uniformity • Shorter disintegration times (Figure 11)
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TECHNICAL
INFORMATION
7
greater 250
hardness less
6
Tensile Strength [MPa]
friction
Ejection Force [N]
200
5
4 150
3
100
50
1 Formulation 1 with PROSOLV ® EASYtab SP Formulation 1 with PROSOLV ® EASYtab SP
Formulation 2 with the Dry Blend Formulation 2 with the Dry Blend
0 0
0 1 2 3 4 5 6 7 8 9 10 11 0 1 2 3 4 5 6 7 8 9 10 11
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Dissolution Comparison with Hydrochlorothiazide
100 100
90 90
80 80
Disolved Active [%]
60 60
50 50
40 40
30 30
20 20
10
Formulation 2 with the Dry Blend 10
Formulation 1 with PROSOLV ® EASYtab SP
0 0
0 15 30 45 60 75 90 105 120 135 150 165 180 195 210 225 240 255 270 285 0 15 30 45 60 75 90 105 120 135 150 165 180 195 210 225 240 255 270 285
Dissolution test of six randomly selected tablets with Formulation 2 Dissolution test of six randomly selected tablets with Formulation 1
(Figure 16): PROSOLV ® EASYtab SP (Figure 17):
• Four tablets pass the USP-NLT 75 % in 45 min, two failed • All tablets pass the USP-NLT 75 % in 45 min
• Inconsistent dissolution results • Very low standard deviation in the dissolution rate (8 %)
• High standard deviation in the dissolution rate (30 %) • Superior formulation robustness
• Low formulation robustness
20
• 25 – 50 % lower ejection forces; especially
shorter at high compression forces (Figure 14)
disintegration
time
10 • Shorter disintegration times (Figure 15)
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TECHNICAL
INFORMATION
Overall Summary:
Dissolution Behavior In the case of Propanolol HCl, Diclofenac Sodium, and Atenolol,
the dissolution profiles of PROSOLV ® EASYtab SP and traditional
formulations were equivalent, passing the USP, NLT 75 % in 45 min
requirement.
For Hydrochlorothiazide, the PROSOLV ® EASYtab SP formulation
showed highly reproducible dissolution results and better formulation
robustness compared to the traditional blend prepared using the
individual ingredients.
Blend Homogeneity In all cases PROSOLV ® EASYtab SP showed much better uniformity in
Tablet Uniformity terms of tablet hardness, weight and API content.
Tablet Coatability PROSOLV ® EASYtab also produced smoother tablet surfaces which
Tablet Physical Appearance lead to better film coating adhesion and a more pronounced logo
embossing. (Additional technical information available).
4 mm
Disclaimer:
The information provided in this brochure is based on thorough research and is believed
to be completely reliable. Application suggestions are given to assist our customers, but
are for guidance only. Circumstances in which our material is used vary and are beyond
our control. Therefore, we cannot assume any responsibility for risks or liabilities, which
may result from the use of this technical advice.
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10 Reasons to Choose PROSOLV EASYtab® All-in-one Composite
11 www.jrspharma.com
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