FMC Alubra brochure8 comp:Layout 1

FMC BioPolymer
Our lubricant brings more to the tablet.
Product Benefits:
Lubricants are a vital part of the tableting manufacture
process. Formulators have typically selected magnesium
stearate to meet these needs as a familiar, well-established
lubricant.
Compared with the widely used lubricant
magnesium stearate, Alubra™ offers:
Enhanced dissolution
Given today’s challenges in formulating tablets, it is important
to ensure that the lubricant choice does not have a negative
impact on disintegration and dissolution. Scientific evidence
demonstrates that magnesium stearate can negatively impact
disintegration and dissolution1. Formulators need to consider
these variables before selecting the appropriate lubricant for
their formulation.
Compatibility with a range of APIs
Flexibility in blending
Improved compactability
Alubra™ has important solubility benefits that can be used
to advantage in developing poorly soluble drugs, orally
disintegrating tablets (ODTs)2, and effervescent dosage forms,
which all require more water-soluble type lubricants than
magnesium stearate.
Alubra™ enhances dissolution of poorly
soluble APIs.
Comparative Dissolution Properties
of 500mg Acetaminophen Tablets
Many of the new generation APIs are poorly soluble, creating
new challenges for tablet manufacturers.
120
While it is today’s most widely used lubricant, magnesium
stearate is very hydrophobic and has detrimental effects on
the dissolution profile of APIs1, especially poorly soluble APIs3.
As a highly soluble lubricant, Alubra™ sodium stearyl fumarate
has shown improved disintegration times in hydrophilic matrix
formations4 and ODTs2 when compared to magnesium stearate.
Magnesium stearate tends to form ‘envelopes’ around API
particles, slowing tablet disintegration and API dissolution, as
opposed to the more hydrophilic Alubra™, which promotes
faster API dissolution of poorly soluble APIs.
100
% API released
Alubra™ offers improved API dissolution.
80
98% acetaminophen + 2% Alubra™
(Hardness 108N; relative density 85.35%)
98% acetaminophen + 2% MgSt
(Hardness 119N; relative density 87.85%)
60
40
20
0
5
10
15
20
25
30
35
40
45
50
55
60
65
Time (min)
Similar lubrication performance
Source: FMC BioPolymer 2010
Better tablet quality
Alubra delivers better dissolution and much more.
™
In addition to offering improved water dispersability of the
molecule, the fumarate moiety of Alubra™ increases the
melting temperature, which allows greater functionality at high
press speeds when compared to magnesium stearate. The
stearate chain of Alubra™ maintains the lubricity of the compound,
supporting low ejection forces.
Chemical structure of Alubra™
sodium stearyl fumarate
HO
O
Typical Alubra™ Properties
Molecular Formula:
C22H39NaO4
Formula Weight:
390.53
Melting Point:
220-240° C
Recommended Use level:
0.5-2.0% of Formulation
Chemical name:
2-Butenedioic
acidiconoctadecyl ester,
sodium salt
Acidity:
pH 8.3 (5% water solution
at 90° C)
Solubility:
acetone practically insoluble
ethanol practically insoluble
methanol slightly soluble
Water 1:5 90° C
Water 1:20,000 25° C
Particle morphology of Alubra™
O
ONa +
Density (bulk):
0.3 to 0.5 g/cc
Density (tapped):
0.4 to 0.6 g/cc
EINECS #:
223-781-1
CID #:
23665634
CAS No.
4070-80-8
Alubra™ offers the lubrication performance
you want.
Comparative Ejection Forces
During manufacture, an extensive amount of friction is generated
between the tablet and the surfaces of the die and punch as
the tablet is ejected. This can impart considerable amounts of
strain and shear to a tablet, resulting in defects such as sticking,
capping, and lamination.
Lubricants like magnesium stearate and sodium stearyl fumarate
have a notable effect in reducing ejection forces. The higher
the ejection force, the greater the possibility that costly tablet
defects will occur.
300
250
Ejection Force (N)
The chemistry of Alubra™ provides important
advantages.
200
Avicel® PH-102 neat
150
Avicel® PH-102 + 1% Alubra™
Avicel® PH-102 + 1% MgSt
100
50
The chemistry of Alubra™ sodium stearyl fumarate is unique
in promoting improved wettability of the tablet while still allowing
for high formulation lubricity, especially at higher tableting
speeds. Under the high melting temperatures that result,
Alubra™ allows prolonged compression times at higher
compression forces. Test results indicate that Alubra™ is equal
to magnesium stearate when it comes to ejection forces.
0
5
10
15
20
25
Compression Force (kN)
Source: FMC BioPolymer 2010
30
35
Product Benefits:
Lubricants are a vital part of the tableting manufacture
process. Formulators have typically selected magnesium
stearate to meet these needs as a familiar, well-established
lubricant.
Compared with the widely used lubricant
magnesium stearate, Alubra™ offers:
Enhanced dissolution
Given today’s challenges in formulating tablets, it is important
to ensure that the lubricant choice does not have a negative
impact on disintegration and dissolution. Scientific evidence
demonstrates that magnesium stearate can negatively impact
disintegration and dissolution1. Formulators need to consider
these variables before selecting the appropriate lubricant for
their formulation.
Compatibility with a range of APIs
Flexibility in blending
Improved compactability
Alubra™ has important solubility benefits that can be used
to advantage in developing poorly soluble drugs, orally
disintegrating tablets (ODTs)2, and effervescent dosage forms,
which all require more water-soluble type lubricants than
magnesium stearate.
Alubra™ enhances dissolution of poorly
soluble APIs.
Comparative Dissolution Properties
of 500mg Acetaminophen Tablets
Many of the new generation APIs are poorly soluble, creating
new challenges for tablet manufacturers.
120
While it is today’s most widely used lubricant, magnesium
stearate is very hydrophobic and has detrimental effects on
the dissolution profile of APIs1, especially poorly soluble APIs3.
As a highly soluble lubricant, Alubra™ sodium stearyl fumarate
has shown improved disintegration times in hydrophilic matrix
formations4 and ODTs2 when compared to magnesium stearate.
Magnesium stearate tends to form ‘envelopes’ around API
particles, slowing tablet disintegration and API dissolution, as
opposed to the more hydrophilic Alubra™, which promotes
faster API dissolution of poorly soluble APIs.
100
% API released
Alubra™ offers improved API dissolution.
80
98% acetaminophen + 2% Alubra™
(Hardness 108N; relative density 85.35%)
98% acetaminophen + 2% MgSt
(Hardness 119N; relative density 87.85%)
60
40
20
0
5
10
15
20
25
30
35
40
45
50
55
60
65
Time (min)
Similar lubrication performance
Source: FMC BioPolymer 2010
Better tablet quality
Alubra delivers better dissolution and much more.
™
In addition to offering improved water dispersability of the
molecule, the fumarate moiety of Alubra™ increases the
melting temperature, which allows greater functionality at high
press speeds when compared to magnesium stearate. The
stearate chain of Alubra™ maintains the lubricity of the compound,
supporting low ejection forces.
Chemical structure of Alubra™
sodium stearyl fumarate
HO
O
Typical Alubra™ Properties
Molecular Formula:
C22H39NaO4
Formula Weight:
390.53
Melting Point:
220-240° C
Recommended Use level:
0.5-2.0% of Formulation
Chemical name:
2-Butenedioic
acidiconoctadecyl ester,
sodium salt
Acidity:
pH 8.3 (5% water solution
at 90° C)
Solubility:
acetone practically insoluble
ethanol practically insoluble
methanol slightly soluble
Water 1:5 90° C
Water 1:20,000 25° C
Particle morphology of Alubra™
O
ONa +
Density (bulk):
0.3 to 0.5 g/cc
Density (tapped):
0.4 to 0.6 g/cc
EINECS #:
223-781-1
CID #:
23665634
CAS No.
4070-80-8
Alubra™ offers the lubrication performance
you want.
Comparative Ejection Forces
During manufacture, an extensive amount of friction is generated
between the tablet and the surfaces of the die and punch as
the tablet is ejected. This can impart considerable amounts of
strain and shear to a tablet, resulting in defects such as sticking,
capping, and lamination.
Lubricants like magnesium stearate and sodium stearyl fumarate
have a notable effect in reducing ejection forces. The higher
the ejection force, the greater the possibility that costly tablet
defects will occur.
300
250
Ejection Force (N)
The chemistry of Alubra™ provides important
advantages.
200
Avicel® PH-102 neat
150
Avicel® PH-102 + 1% Alubra™
Avicel® PH-102 + 1% MgSt
100
50
The chemistry of Alubra™ sodium stearyl fumarate is unique
in promoting improved wettability of the tablet while still allowing
for high formulation lubricity, especially at higher tableting
speeds. Under the high melting temperatures that result,
Alubra™ allows prolonged compression times at higher
compression forces. Test results indicate that Alubra™ is equal
to magnesium stearate when it comes to ejection forces.
0
5
10
15
20
25
Compression Force (kN)
Source: FMC BioPolymer 2010
30
35
Alubra™ provides greater tablet strength.
Comparative Tablet Hardness
500
450
400
Hardness (N)
Trials were run on Alubra™ to evaluate its compression
performance versus magnesium stearate. The results indicate
that Alubra™ offers superior compression versus magnesium
stearate across the complete compression profile. Furthermore,
Alubra™ shows no drop-off in hardness versus magnesium
stearate at higher compression forces.
350
Avicel® PH-102 neat
300
Avicel® PH-102 + 1% Alubra™
250
Avicel® PH-102 + 1% MgSt
200
150
When compactability was measured on a rotary press, the
blend using Alubra™ resulted in the hardest tablets, indicating
that Alubra™ is a better choice than magnesium stearate when
it comes to high-speed tableting, and/or higher compression
forces.
100
50
0
5
10
15
20
25
30
35
Compression Force (kN)
Source: FMC BioPolymer 2010
PROCEDURE
FORMULA
Ingredient
%Formula
Avicel PH-102:
Alubra™ or Magnesium Stearate:
®
99
1
• Materials: Avicel® PH-102 + 1% lubricant
(Alubra™ or MgSt) and Avicel® PH-102 neat
• One set of round, normal concave, D-type,
12 mm diameter punches (position #1)
• Sieved through 710µm
• Tablet weight: 500 mg
• Blending time 5 minutes
• Rotation speed: 34 RPM
• Rotary press: Manesty D4
• Compression force: 5, 10, 15, 20, 25, 30 kN
(for Avicel® PH-102 neat: 2, 4, 8, 12, 16, 20 kN)
tablet strength and quality.
Alubra™ Commercial Information
Alubra™ meets the highest quality standards.
Alubra™ complies with all major pharmacopoeias:
Alubra™ is manufactured under IPEC and cGMP conditions,
which comply with recognized global quality standards. FMC’s
own quality initiatives are designed to produce a lubricant that
is chemically, physically, and functionally consistent, as well
as compliant with the stringent requirements of all major
pharmacopoeias. FMC carries out systematic product evaluation
to ensure that Alubra™ continues to meet or surpass these
high standards.
Alubra™ sodium stearyl fumarate is included in the FDA
Inactive Ingredient Database for oral capsules and tablets,
as well as in the Canadian List of Acceptable Non-Medicinal
Ingredients.
1. Chowhan, Z.T. and Chi, L.H. (1986); Drug Excipient Interactions Resulting from
Powder Mixing IV: Role of Lubricants and their Effect on In Vitro Dissolution ;
Journal of Pharmaceutical Sciences, 75: 542-545. doi: 10.1002/jps.2600750604
2. Gebert, K. Meyer-Bohm, A. Maschke and K. Kolter; Compression Characterization
and Lubricant Sensitivity of Orally Disintegrating Tablets Based on Lubiflash ;
Pharmaceutical Technology Europe, January 1, 2009, Volume 21, Issue 1
• NF
• JPE
• PH. Eur.
• BP
• CP
Commercial packaging:
• 1 KG (fiber)
• 5 KG (fiber)
• 20 KG (fiber)
Available supporting documentation for Alubra™:
• Specification Sheet
• MSDS
• COAs
• BSE/TSE Certificate
• GMO Certificate (Generally Modified Organism)
• Residual Solvent Certification (as per USP Chapter 467)
• Not of Human/Animal Origin Certificate
• Allergen-Free Certificate
3. G.K. Bolhuis, C.F. Lerk, H.T. Zijlstra and A.H. de Boer; Pharm. Weekblad 110 317
(1975)
4. Tommasina Coviello, Antonio Palleschi, Mario Grassi, Pietro Matricardi, Gianfranco
Bocchinfuso and Franco Alhaique; Scleroglucan: A Versatile Polysaccharide for
Modified Drug Delivery ; Molecules 31, January 2005, 10, 6-33
Alubra™ provides greater tablet strength.
Comparative Tablet Hardness
500
450
400
Hardness (N)
Trials were run on Alubra™ to evaluate its compression
performance versus magnesium stearate. The results indicate
that Alubra™ offers superior compression versus magnesium
stearate across the complete compression profile. Furthermore,
Alubra™ shows no drop-off in hardness versus magnesium
stearate at higher compression forces.
350
Avicel® PH-102 neat
300
Avicel® PH-102 + 1% Alubra™
250
Avicel® PH-102 + 1% MgSt
200
150
When compactability was measured on a rotary press, the
blend using Alubra™ resulted in the hardest tablets, indicating
that Alubra™ is a better choice than magnesium stearate when
it comes to high-speed tableting, and/or higher compression
forces.
100
50
0
5
10
15
20
25
30
35
Compression Force (kN)
Source: FMC BioPolymer 2010
PROCEDURE
FORMULA
Ingredient
%Formula
Avicel PH-102:
Alubra™ or Magnesium Stearate:
®
99
1
• Materials: Avicel® PH-102 + 1% lubricant
(Alubra™ or MgSt) and Avicel® PH-102 neat
• One set of round, normal concave, D-type,
12 mm diameter punches (position #1)
• Sieved through 710µm
• Tablet weight: 500 mg
• Blending time 5 minutes
• Rotation speed: 34 RPM
• Rotary press: Manesty D4
• Compression force: 5, 10, 15, 20, 25, 30 kN
(for Avicel® PH-102 neat: 2, 4, 8, 12, 16, 20 kN)
tablet strength and quality.
Alubra™ Commercial Information
Alubra™ meets the highest quality standards.
Alubra™ complies with all major pharmacopoeias:
Alubra™ is manufactured under IPEC and cGMP conditions,
which comply with recognized global quality standards. FMC’s
own quality initiatives are designed to produce a lubricant that
is chemically, physically, and functionally consistent, as well
as compliant with the stringent requirements of all major
pharmacopoeias. FMC carries out systematic product evaluation
to ensure that Alubra™ continues to meet or surpass these
high standards.
Alubra™ sodium stearyl fumarate is included in the FDA
Inactive Ingredient Database for oral capsules and tablets,
as well as in the Canadian List of Acceptable Non-Medicinal
Ingredients.
1. Chowhan, Z.T. and Chi, L.H. (1986); Drug Excipient Interactions Resulting from
Powder Mixing IV: Role of Lubricants and their Effect on In Vitro Dissolution ;
Journal of Pharmaceutical Sciences, 75: 542-545. doi: 10.1002/jps.2600750604
2. Gebert, K. Meyer-Bohm, A. Maschke and K. Kolter; Compression Characterization
and Lubricant Sensitivity of Orally Disintegrating Tablets Based on Lubiflash ;
Pharmaceutical Technology Europe, January 1, 2009, Volume 21, Issue 1
• NF
• JPE
• PH. Eur.
• BP
• CP
Commercial packaging:
• 1 KG (fiber)
• 5 KG (fiber)
• 20 KG (fiber)
Available supporting documentation for Alubra™:
• Specification Sheet
• MSDS
• COAs
• BSE/TSE Certificate
• GMO Certificate (Generally Modified Organism)
• Residual Solvent Certification (as per USP Chapter 467)
• Not of Human/Animal Origin Certificate
• Allergen-Free Certificate
3. G.K. Bolhuis, C.F. Lerk, H.T. Zijlstra and A.H. de Boer; Pharm. Weekblad 110 317
(1975)
4. Tommasina Coviello, Antonio Palleschi, Mario Grassi, Pietro Matricardi, Gianfranco
Bocchinfuso and Franco Alhaique; Scleroglucan: A Versatile Polysaccharide for
Modified Drug Delivery ; Molecules 31, January 2005, 10, 6-33
FMC is today’s global leader in high-quality excipients for pharmaceuticals and supplements.
As the world’s leading manufacturer of high-quality pharmaceutical and supplement excipients, FMC has extensive experience
in formulation and processing. When customers use Alubra™, they get the benefit of this unparalleled experience, in the form
of exceptional technical support.
FMC’s technical service professionals perform a number of essential tasks for customers, including conducting functionality,
stability, and other tests, helping customers find solutions to their processing problems, conducting training for customer
personnel, and providing access to comprehensive reference libraries.
For further information on FMC’s outstanding products and services, contact us at 1-800-526-3649 or go to our website at
www.fmc.com
Sales Offices
United States
Philadelphia, PA
Europe
Brussels, Belgium
Asia-Pacific
Hong Kong
Latin America
Montevideo, Uruguay
Sales/Technical
Assistance:
Tel: 1-215-299-6534
Fax: 1-215-299-6669
Sales/Technical
Assistance:
Tel: +32-2-775-8311
Fax: +32-2-775-8300
Tel: +852-2839-6600
Fax: +852-2576-3770
Tel/Fax: +5982-6043030
Tel/Fax: +5882-6043104
Tokyo, Japan
Middle East
Amman, Jordan
Customer Service:
Tel: 1-800-526-3649
Fax: 1-215-299-6475
Customer Service:
Tel: +353-21-4354-133
Fax: +353-21-4353-057
Tel: +81-3-3402-3739
Fax: +81-3-3402-3700
Tel: +962-5-4618150
Fax: +962-5-4618156
Patents
FMC Corporation is owner and/or licensee of several patents related to its products. The products, processes, and uses of such products referred to in this document may be covered by
one or more patents or pending applications in the United States and/or other countries. FMC does not warrant against any infringement claim arising from the sales and/or use of any
FMC product in combination with other materials; the use of any FMC product in the operation of any process; any FMC product manufactured to a customer’s designs or specifications;
or any FMC product manufactured by any process requested by a purchaser.
Product Suitability
The information contained in this document (as well as any advice or assistance) is provided by FMC only as a courtesy and is intended to be general in nature. Any uses suggested
by FMC are presented only to assist our customers in exploring possible applications. FMC makes no warranty, express or implied, as to its accuracy or completeness, or the results
to be obtained from such information, advice, or assistance. Each customer is solely responsible for determining whether the FMC products are suitable for each customer’s intended
use, and for obtaining any necessary governmental registrations and approvals for such customer’s production, marketing, sale, use and/or transportation of finished goods using or
incorporating the FMC products.
www.fmcbiopolymer.com/pharmaceutical
[email protected]
FMC logo, Alubra and Avicel are trademarks of FMC Corporation.
© 2010 FMC Corporation. All rights reserved. Alubra.09.2010-1.PTG