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TECHNICAL

INFORMATION

The Performance of PROSOLV ® EASYtab SP in Four Medium-Dose, Direct


Compression Formulations with Morphologically Challenging Model APIs

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

Pic. 1 SEM Picture of PROSOLV EASYtab SP


®

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)

API Solubility Particle Size / Main Challenge


Shape
Propanolol HCI high fine flowability,
weight uniformity
Diclofenac low coarse / demixing,
spherical content uniformity
Atenolol high flaky mixing properties,
uniformity
Hydrochlorothiazide low even, uniformity of lubrication,
flat surface dissolution
Tab. 1 Properties of selected model APIs

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TECHNICAL
INFORMATION

Case Study – Propranolol Hydrochloride

High Solubility, Fine Particle API

Parameter Formulation 1 Formulation 2


PROSOLV ® EASYtab SP Dry Blend
mg % mg %
Propranolol HCl 40.00 20.00 40.00 20.00
PROSOLV EASYtab SP ®
160.00 80.00 – –
VIVAPUR® 102 – – 154.40 77.20
Colloidal Silicon Dioxide – – 3.20 1.60
EXPLOTAB® – – 1.60 0.80
Sodium Starch Glycolate
PRUV ® – – 0.80 0.40
Sodium Stearyl Fumarate
Total 200.00 100.00 200.00 100.00 x 1,0k 100 µm

Tab. 2 Propranolol Hydrochloride Formulation Pic. 2 Propranolol Hydrochloride

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

Compression Force [kN] Tensile Strength [MPa]

Fig. 1 Compressibility of Propranolol Hydrochloride Fig. 2 Disintegration of Propranolol Hydrochloride

20 – 30 % better compressibility Shorter disintegration times

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500 100

90
450
less
friction

Disolved Active [%]


80
Ejection Force [N]

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

Compression Force [kN] Time [min]

Fig. 3 Ejection Forces of Propranolol Hydrochloride Fig. 4 Dissolution of Propranolol Hydrochloride


(USP - Aparatus II, 50 rpm Deionized H2O)

30 – 40 % lower ejection forces Equivalent dissolution times. Dissolution test –


pass USP-NLT 75 % in 45 min (100 % in 15 min)

Relative Standard Deviation Conclusions


Uniformity Formulation 1 Formulation 2
PROSOLV ® EASYtab SP Dry Blend
Compared to the physical mixture PROSOLV ® EASYtab SP shows:
Tablet Hardness Uniformity 2.38 % 3.85 %
Tablet Weight Uniformity 0.16 % 0.54 % • 20 – 30 % better compressibility (Figure 1)

API Content Uniformity 1.29 % 4.47 % • 30 – 40 % lower ejection forces (Figure 2)


Tab. 3 Propranolol Hydrochloride – Formulation Uniformity • Shorter disintegration times (Figure 3)

• Equivalent dissolution times. Dissolution test – pass USP-NLT


75 % in 45 min (100 % in 15 min, Figure 4)
• Improved tablet hardness, weight and content uniformity
(Table 3) in spite of poor API flow.

The uniformity values above in Tab. 3 demonstrate that


PROSOLV ® EASYtab is capable of overcoming the negative
API properties in terms of flow.

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TECHNICAL
INFORMATION

Case Study – Diclofenac Sodium

Low Solubility,Coarse API

Parameter Formulation 1 Formulation 2


PROSOLV ® EASYtab SP Dry Blend
mg % mg %
Diclofenac Sodium 25.00 12.50 25.00 12.50
PROSOLV ® EASYtab SP 175.00 87.50 – –
VIVAPUR 102 ®
– – 168.86 84.43
Colloidal Silicon Dioxide – – 3.50 1.75
EXPLOTAB ®
– – 1.76 0.88
Sodium Starch Glycolate
PRUV ® – – 0.88 0.44 x 800 100 µm
Sodium Stearyl Fumarate
Total 200.00 100.00 200.00 100.00 x 800 100 µm

Tab. 4 Diclofenac Sodium Formulation Pic. 3 Diclofenac Sodium

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]

Fig. 5 Compressibility of Diclofenac Sodium Fig.6 Disintegration of Diclofenac Sodium

30 – 35 % better compressibility Shorter disintegration times

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100
500
90

450 80

Disolved Active [%]


Ejection Force [N]

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

Compression Force [kN] Time [min]


Fig. 7 Ejection Forces of Diclofenac Sodium Fig. 8 Dissolution of Diclofenac Sodium (USP - Aparatus II, 50 rpm Deionized H2O)

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).

Relative Standard Division Conclusions


Uniformity Formulation 1 Formulation 2
PROSOLV ® EASYtab SP Dry Blend
Compared to the physical mixture:
Tablet Hardness Uniformity 1.77 % 4.18 %
Tablet Weight Uniformity 0.23 % 0.52 % • 30 – 35 % better compressibility (Figure 5)

API Content Uniformity 1.02 % 2.70 % • 20 % lower ejection forces;


Tab. 5 Diclofenac Sodium – Formulation Uniformity especially at high compression forces (Figure 6)
Tablet and content uniformity due to the API's size and shape • Shorter disintegration times (Figure 7)
are improved by PROSOLV ® EASYtab. • Equivalent dissolution times
Dissolution test – pass USP-NLT 75 % in 45 min
(100 % in 5 min, Figure 8)
• Improved, weight and content uniformity
in spite of demixing tendency (Table 5)

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TECHNICAL
INFORMATION

Case Study – Atenolol

High Solubility, Flaky

Parameter Formulation 1 Formulation 2


PROSOLV ® EASYtab SP Dry Blend
mg % mg %
Atenolol 50.00 25.00 50.00 25.00
PROSOLV ® EASYtab SP 150.00 75.00 – –
VIVAPUR 102 ®
– – 144.74 72.37
Colloidal Silicon Dioxide – – 3.00 1.50
EXPLOTAB ®
– – 1.50 0.75
Sodium Starch Glycolate
PRUV ® – – 0.76 0.38
Sodium Stearyl Fumarate x 800 100 µm
x 800 100 µm
Total 200.00 100.00 200.00 100.00
Tab. 6 Atenolol Formulation Pic. 4 Atenolol

Formulation 1 with PROSOLV ® EASYtab SP 220 Formulation 1 with PROSOLV ® EASYtab SP


4.50
Formulation 2 with the Dry Blend 200 Formulation 2 with the Dry Blend
4.00
greater 180
Disintegration Time [s]

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

Compression Force [kN] Tensile Strength [MPa]


Fig. 9 Compressibility of Atenolol Fig. 10 Disintegration of Atenolol

20 % better compressibility Shorter disintegration times

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390 100
380
less 90
370 friction 80

Disolved Active [%]


Ejection Force [N]

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

Compression Force [kN] Time [min]


Fig. 11 Ejection Forces of Atenolol Fig. 12 Dissolution of Atenolol (USP - Aparatus II, 50 rpm Deionized H2O)

10 – 15 % lower ejection forces Equivalent dissolution times. Dissolution test –


pass USP-NLT 75 % in 45 min (95 % in 15 min).

Relative Standard Divisoion Conclusions


Uniformity Formulation 1 Formulation 2
PROSOLV ® EASYtab SP Dry Blend
Compared to the physical mixture PROSOLV ® EASYtab SP shows:
Tablet Hardness Uniformity 1.99 % 2.47 %
Tablet Weight Uniformity 0.26 % 0.75 % • 20 % better compressibility (Figure 9)

API Content Uniformity 0.74 % 7.93 % • 10 – 15 % lower ejection forces (Figure 10)
Tab. 7 Atenolol – Formulation Uniformity • Shorter disintegration times (Figure 11)

• Equivalent dissolution times. Dissolution test – pass USP-NLT


The flaky structure of the API leads to content uniformity issue 75 % in 45 min (95 % in 15 min, Figure 12)
which is addressed by PROSOLV ® EASYtab. • Improved hardness and weight uniformity (Table 7)

• 10 times better content uniformity (Table 7) in spite of


challenging structure of the API.

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TECHNICAL
INFORMATION

Case Study – Hydrochlorothiazide

Low Solubility, Plate-like Structure

Parameter Formulation 1 Formulation 2


PROSOLV ® EASYtab SP Dry Blend
mg % mg %
Hydrochlorothiazide 25.00 12.50 25.00 12.50
PROSOLV ® EASYtab SP 175.00 87.50 – –
VIVAPUR® 102 – – 168.86 84.43
Colloidal Silicon Dioxide – – 3.50 1.75
EXPLOTAB ®
– – 1.76 0.88
Sodium Starch Glycolate
x 800 100 µm
PRUV ® – – 0.88 0.44
Sodium Stearyl Fumarate
x 800 100 µm
Total 200.00 100.00 200.00 100.00
Tab. 8 Hydrochlorothiazide Formulation Pic. 5 Hydrochlorothiazide

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

Compression Force [kN] Compression Force [kN]


Fig. 13 Compressibility of Hydrochlorothiazide Fig. 15 Ejection Forces of Hydrochlorothiazide

20 – 30 % better compressibility 25 – 50 % lower ejection forces; especially at high compression


forces

Relative Standard Deviation


Uniformity Formulation 1 Formulation 2
PROSOLV ® EASYtab SP Dry Blend
Tablet Hardness Uniformity 1.88 % 4.33 %
Tablet Weight Uniformity 0.26 % 0.41 %
API Content Uniformity 1.00 % 3.93 %
Tab. 9 Hydrochlorothiazide – Formulation Uniformity

Improved tablet hardness, weight and content uniformity (Table 9)

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Dissolution Comparison with Hydrochlorothiazide

100 100

90 90

80 80
Disolved Active [%]

Disolved Active [%]


70 70

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

Time [min] Time [min]


Fig. 16 Dissolution of Hydrochlorothiazide with the Physical Mixture – 6 Tablets Fig. 17 Dissolution of Hydrochlorothiazide with PROSOLV® EASYtab – 6 Tablets
(USP - Apparatus II, 50 rpm Deionized H2O)

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

Formulation 1 with PROSOLV ® EASYtab SP Conclusions


Formulation 2 with the Dry Blend
40
Compared to the physical mixture
Disintegration Time [s]

PROSOLV ® EASYtab SP shows:


30
• 20 – 30 % better compressibility (Figure 13)

20
• 25 – 50 % lower ejection forces; especially
shorter at high compression forces (Figure 14)
disintegration
time
10 • Shorter disintegration times (Figure 15)

• Improved hardness, weight and content uniformity


0
0.00 1.00 2.00 3.00 4.00 5.00 6.00
(Table 9)
Tensile Strength [MPa] • Highly consistent dissolution rates, as composite structure
Fig. 14 Disintegration of Hydrochlorothiazide prevents accumulation of lubricants on the plate-like API
surface. (Figure 17)
Shorter disintegration times

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TECHNICAL
INFORMATION

Overall Summary:

Compaction In all cases, PROSOLV ® EASYtab SP showed better compactibility


Lubrication Efficiency resulting in 20 - 35 % harder tablets, lower ejection forces, and shorter
Disintegration disintegration times compared to the dry blend of the single
components.

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

Would you like to receive a sample?


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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.

www.jrspharma.com 10
10 Reasons to Choose PROSOLV EASYtab® All-in-one Composite

1. Coprocessed all in one ready-to-use composite


for direct compression and continuous processing.
2. Superior API content uniformity.
3. Up to 40 % harder tablets with less friability
compared to physical blend
4. Outstanding logo definition and film adhesion to
the core.
5. Shorter development times
• Faster market entry
• Less experiments needed
6. Three times faster tableting increases your
capacity without additional investments. 100 µm

7. Wide range of pharma and nutra grades.


8. Upcoming monograph reduces time effort for
registration.
9. The use of only one instead of 4 excipients
cuts down handling, storage and QC costs.
10. Global service network with local technical and
operational support

Product Overview PROSOLV EASYtab®

Filler/Binder Flow Aid Disintegrant Lubricant


Grades Developed Microcrystalline Colloidal Silicon Croscarmellose Sodium Starch Sodium Stearyl Magnesium
for Cellulose Dioxide Sodium Glycolate Fumarate Stearate

PROSOLV ® EASYtab SP Phr. Eur., NF, JPE x x x x


PROSOLV ® EASYtab SP LM Phr. Eur., NF, JPE x x x x
PROSOLV EASYtab Nutra CM
®
Russia, Brazil, x x x x
EU, and USA
PROSOLV ® EASYtab Nutra GM China, Korea x x x x
PROSOLV ® EASYtab Nutra CP USA x x x x

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