PROSOLV ® SMCC

High Functionality Excipient

Problem Solving for

over 25 years.

Smaller Tablets
Harder Tablets
Faster Output
 PROSOLV ® SMCC
Silicified Microcrystalline Cellulose, NF

Introduction Effects of PROSOLV ® Technology

Excipients play a major role in the development of Co-processing of MCC with CSD using the PROSOLV ®
tablets and capsules for the health science industry. technology leads to a homogenous distribution of CSD
As APIs and manufacturing processes evolve, the need particles throughout the product and on the particle
for excipients with greater functionality increases. surfaces.

Over 25 years ago JRS PHARMA developed a new high At low magnification, traditional MCC and SMCC look
functionality excipient, PROSOLV ® SMCC, with enhanced very similar in terms of their particle size and shape.
properties for modern, high-speed tableting processes. At high magnification, however, electron microscopy
reveals the differences in the microstructures of the
PROSOLV ® SMCC provides solutions to problems
silicified MCC PROSOLV ® SMCC (Picture 1) and tradi-
formulators often encounter with conventional binders
tional MCC (Picture 2).
in terms of low bulk density, poor flow, loss of compac-
tability, stickiness issues and sensitivity to lubricants. Silicification reduces the cohesiveness of the powder
bed. Consequently, it has much better powder flowa-
PROSOLV ® SMCC addresses these challenges and
bility than traditional MCC grades of the same particle
offers additional benefits.
size leading to more manufacturing output, via high-
speed tableting.

Physical Properties of PROSOLV ® SMCC Compared to traditional MCC, the unique surface struc-
ture of PROSOLV ® SMCC enables excellent blend homo-
• White, free flowing powder geneity and content uniformity, even for low-dose, mi-
• High degree of brightness cronized active ingredients.
• Practically insoluble in water, acetone, Lastly, PROSOLV ® SMCC exhibits a 5 times increased
and anhydrous ethanol surface area thus improving the outstanding binding
• Chemically inert properties of MCC (Figure 1). This makes PROSOLV ® SMCC
• Excellent compactability an ideal choice for high dose, direct compression for-
mulations and roller compaction processes*
• High intrinsic flow *Technical information available
• Enhanced lubrication efficiency BET - Specific Surface Area [m2/g]
• Improved blending properties MCC

• Five times greater specific surface area than PROSOLV ®

SMCC
Microcrystalline Cellulose (MCC) alone
0 1 2 3 4 5 6
2
• Dust free Colloidal Anhydrous Silica (CSD) handling m /g
Fig. 1 5 Fold Increase in Specific Surface Area.

Pic. 1 PROSOLV ® SMCC 90 Pic. 2 Traditional Microcrystalline Cellulose.

High Magnification SEMs Show CSD Particles Tightly Bound to the MCC Surfaces
and Pores.

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 Performance of Various Grades of Benefits
®
PROSOLV SMCC
PROSOLV ® SMCC provides unique technical and
manufacturing benefits throughout the product
Tensile Strength [MPa] at 10 kN Compression Force

PROSOLV ® SMCC 50 LD
lifecycle including:
Better Hardness

7
PROSOLV ® SMCC 50
6 VIVAPUR ® 105
PROSOLV ® SMCC 90 • Rapid formulation development
5
VIVAPUR ® 101 VIVAPUR ® 102 PROSOLV ® SMCC • Dust-free handling
VIVAPUR ® 301 HD90
VIVAPUR 302
®

4
VIVAPUR ® 12 ®
VIVAPUR 200
• Superior flow
3 • Improved compactability, leading to more robust
tablets
2

• Fewer excipients needed at lower use levels

1

Better Flowability • Smaller tablet size

0
65 60 55 50 45 40 35 30 25 20
Flowability as Angle of Repose [°]
• Enhanced mixing characteristics
®
Fig. 2 PROSOLV SMCC Offers Superior Flowability® and • Optimized content uniformity
Tablet Strength Compared to MCC VIVAPUR .
• Shorter disintegration time
• More production output
®
The wide variety of PROSOLV SMCC grades available
ensures the perfect solution for a range of different
formulation challenges. Typical Reduction of Excipient Usage
with PROSOLV ® SMCC
PROSOLV ® SMCC 50 LD Formulations including PROSOLV ® SMCC typically
Best in class binder. require lower excipient use levels including:

PROSOLV ® SMCC 50 • 30 – 50 % less MCC/binders

Formulas in which optimal compaction and decent • 25 – 50 % less lubricants
flow are required. • 25 – 50 % less disintegrants

PROSOLV ® SMCC 90 • No Dibasic Calcium Phospate (DCP) needed

Formulas in which a balance of flow and compaction • No additional CSD/glidants needed
are required.

PROSOLV ® SMCC HD 90*

Formulas in which optimal flow and consolidation are
required. This grade shows the best disintegration time.

PROSOLV ® SMCC 90 LM
Equivalent to quality of PROSOLV ® SMCC 90, with
lower moisture content (< 3 %).

*For PROSOLV® SMCC HD 90 low moisture grade is available upon request.

3 www.jrspharma.com
 PROSOLV ® SMCC
Silicified Microcrystalline Cellulose, NF

Functional Benefits

Direct Compression Blend Uniformity

Pictures 3 a and 3 b show PROSOLV ® SMCC 90 (left)
PROSOLV SMCC 90
®
and VIVAPUR ® 102 (right) before and after blending
MCC 90 or 102 Grades
14
with red iron oxide.
Tensile Strength [MPa]

12
Good blend uniformity is achieved in both cases.
10
However the PROSOLV ® blend, exhibits a far stronger
8
color intensity than the corresponding MCC blend.
6
This effect can be attributed to the larger specific
4
surface area of SMCC, which promotes blending,
2
and thus content uniformity, for fine-particle APIs.
0

0 2 4 6 8 10 12 14 16 18

Compression Force [kN]

Fig. 3 Comparison of the Compression Profiles of PROSOLV ® SMCC 90
and a Conventional MCC of the Same Particle Size.

PROSOLV ® SMCC is 30 – 50 % more compactible than MCC.

It accommodates poorly compactible APIs, delivers
superior compact a bility in high drug-loading applica-
tions, and excels in roller compaction processes.

Volume Flow
Pic. 3 a PROSOLV ® SMCC (left) and VIVAPUR ® Before Blending with
the Model Substance Iron Oxide Red.
45

40 PROSOLV ® SMCC 90

35
MCC 200
MCC 90 or 102 Grades
30
Flow Rate [g/s]

25

20

15

10

0
2 4 6 8 10 12 14 16 18

Aperture Size [mm]

Fig. 4 Comparison of the Flow Properties of PROSOLV ® SMCC and Different Pic. 3b PROSOLV ® SMCC (left) and VIVAPUR ® 102 After 3 Minutes of Blending
Conventional MCCs. with the Model Substance Iron Oxide Red.

PROSOLV ® SMCC offers a balance of best in class

compaction and flow for tablet formulations.
Silicification provides flow that is comparable to
doubling the particle size of MCC in addition to
superior compaction (Figure 4).

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 Case Study: Reducing Tablet Size for a Higher Drug Load

Formulation Challenges Low Bulk Density,

Multiple-API Formulation
This 19-active formulation, including herbal consti-
tuents, required large amounts of both MCC and DCP
to achieve workable compactibility, yet still exhibited PROSOLV ® SMCC
MCC/DCP Formulation
Formulation
significant segregation, low content uniformity, and
poor flow. The resulting tablet also exceeded target 20 % MCC 7 % PROSOLV ® SMCC 90
size, due to the multiple components and large amount 20 % DCP No DCP required
of excipients. Low compactibility Exceptional tablet
compaction
• Hardness 90 - 120 N
• Friability 0.08 %
Formulation Results
After formulating with PROSOLV ® SMCC the need for Excessive tablet weight Target weight achieved
DCP was eliminated. Compactability, segregation and > 1800 mg < 1300 mg
content uniformity were improved and tablet weight
Low bulk density Consolidated powder
was reduced by 33 %. Finally, due to the improved flow blend with excellent flow
Active with poor flow
characteristics and consolidated blending, tableting • Increased production
speed and production efficiency were both increased. output

Significant segregation Non-segregating

of active formulation
Production Benefits and Efficiencies • Fine particles • Separation of fine
• Reduced binder usage significantly seen floating on particles reduced
top of blend • < 2 % Relative Standard
• Eliminated DCP entirely Deviation(RSD) in
• Reduced tablet weight by 33 % ! tablet weight

• Improved processing characteristics

• Improved tablet content uniformity
• Increased production efficiency, tablets per batch

1080 mg API 1080 mg API

720 mg Filler / Binder 80 mg PROSOLV ® SMCC
1800 mg 1160 mg

Tab. 1 Comparison Between MCC/DCP and PROSOLV ® SMCC Formulation.

5 www.jrspharma.com
 PROSOLV ® SMCC
Silicified Microcrystalline Cellulose, NF

Case Study: Simplifying Formulation Development

of a Low Dose Cohesive Active

Formulation Challenges Formulation

This single active, multi-dose prescription tablet formu- % w/w
Ingredient
lation presented issues with API agglomeration that RLD A B C
challenged blending and content uniformity. A success- API <5 <5 <5 <5
ful outcome was further challenged by targeting a direct Lactose ~ 65
compression tablet manufacturing process. Microcrystalline Cellulose ~ 20 ~56
PROSOLV ® SMCC HD 90 ~ 55 ~ 37 > 95
PROSOLV ® SMCC 50 ~ 36
Formulation Results Colloidal Silicone Dioxide ~9
Croscarmellose Sodium ~2
Through a progressive reformulation strategy, scientists
Talc < 0.6 <5
developed a directly compressible low-dose formulation
Magnesium Stearate > 0.4 > 0.4 > 0.4 < 0.4
suitable for dose proportional, multi-strength tablet ma- Tab. 2 Tested Formulations.
nufacture with excellent content uniformity. The number RLD = Reference Listed Drug API = Active Pharmaceutical Ingredient
SMCC = Silicified Microcrystalline Cellulose A,B = trial formulation
of excipients was reduced from five to two. The lubricant RSD = Relative Standard Deviation C = final formulation

required was also minimized during scale-up.

Production Benefits and Efficiencies Formulation C, Content Uniformity Analysis

• Reduced number of excipients used Ø - Recovery [%]
Time Point RSD [%]
(n=10)
• Fast and simpler formulation development
Beginning 98.6 0.5
• Simplified manufacturing process
Mid 97.1 0.5
• Shortened manufacturing times End 98.7 1.2
• Improved content uniformity Tab. 3 The Final Formulation Exhibited Excellent Content Uniformity
Throughout the Tabletting Run.

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6
 Regulatory Information
Packaging, Samples and Storage
PROSOLV ® SMCC is an agglomerated composite from
Microcrystalline Cellulose Ph.Eur., USP-NF, JP and Storage
Colloidal Silicon Dioxide Ph.Eur., USP-NF, JP (Light Store in original container. Protected from excessive
Anhydrous Silicic Acid JP). It is monographed in the heat and moisture. Opened containers should be
second supplement to NF 27, JPE and is listed in the reclosed or stored in a manner which provides the
Inactive Ingredient Database (IID) on the FDA website product with protection equal to the original.
as an approved ingredient in New Drug Applications
(NDA). There are regulatory approvals in all major Packaging
markets with PROSOLV ® SMCC including: USA, Europe, Available in bags, drums, and supersacks
Japan, Mexico, Australia, India, and China. TUP, QbD Sample Sizes
and elemental impurity studies are available. 400 g and 2 kg containers available

State Regulatory Status

High supply security guaranteed by multiple GMP
Brazil Silicified Microcrystalline Cellulose, NF
Microcrystalline Cellulose, Ph.Eur. production sites across three different continents.
Silica, Colloidal Anhydrous, Ph.Eur.
Microcrystalline Cellulose and Silicon Dioxide are
listed in the positive list for Food Case Studies
Canada Silicified Microcrystalline Cellulose, NF Case studies and formulation examples are available
Product master file 2006-116 with Health Canada upon request. Please contact your sales rep for more
Microcrystalline Cellulose and Silicon Dioxide are
permitted as food additive in information or visit www.jrspharma.com.
Health Canada's Food and Drug Regulations

China Silicified Microcrystalline Cellulose, ChP

IDL available now.
Chinese DMF will be submitted in end of 2018.

Europe Microcrystalline Cellulose, Ph.Eur.

Silica, Colloidal Anhydrous, Ph.Eur.
Upcoming monograph for co-processed excipients
Microcrystalline Cellulose, E 460
Silicon Dioxide, E 551

Japan Silicified Microcrystalline Cellulose, JPE

USA Silicified Microcrystalline Cellulose, NF

SMCC is listed on FDA's Inactive Ingredients
Database, Drug master file number 12150
Microcrystalline Cellulose and Silicon Dioxide are
considered GRAS and listed on FDA's Food Additive
Status List and FDA's Everything Added to
Food in the United States (EAFUS) list
Tab. 4 Regulatory Status.

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
7
 JRS
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www.jrspharma.com
JRS PHARMA GMBH & CO. KG
Business Unit Excipients
73494 Rosenberg (Germany)
Phone: +49 7967 152-312
ExcipientsService@JRSPharma.de