Tokyo Head Office

FREUND Bldg., 6-25-13 Nishishinjuku,Shinjuku-ku, Tokyo 160-0023 Japan
TEL +81-3-6890-0793 FAX +81- 3-6890-0861

PharmaceuticalExcipients

Osaka Office

12-41, Hiroshibacho, Suita-shi, Osaka
564-0052 Japan
TEL +81-6-6338-6747 FAX +81-6-6338-6703

Hamamatsu OfficeInstitute for Technology Development
1-2-2, shin-miyakoda, kita-ku, Hamamatsu-shi
Shizuoka 431-2103 Japan
TEL +81-53-428-4611 FAX +81-53-428-4618
http：//www.freund.co.jp

FREUND CORPORATION
2019.08（02.01）01.Printed in JapanINDEXCompany Profile ……………………………………………… 3DilactoseTM…………………………………………………… 5

GranutolTM ……………………………………………………… 6
NONPAREILTM ………………………………………………… 7
NONPAREILTM-103 …………………………………… 7
NONPAREILTM-105 …………………………………… 8
NONPAREILTM-108 …………………………………… 8
Titanium Oxide FG …………………………………………… 9AdsoliderTM-101 ……………………………………………… 10
LubriwaxTM-101……………………………………………… 11

Polishing Wax -105 ………………………………………… 11
TMCMECTM……………………………………………………… 12

Freund Pharmaceutical Excipients Product Table…… 13-142

Freund’s functional excipients
which meet a variety of needs
Freund succeeded in developing the automatic film coating
equipment and film coating excipient for the first time in theworld after its inception in April 1964 and started thesebusinesses.

Pioneering the future in creativity

Freund’s technology laboratory institute with the experts ofpharmaceutical, food, applied chemical, chemical engineering,biochemistry, electronic engineering, mechanical engineering, has conducted innovative product development, haslaunched many unique products and gained high evaluationfrom various field.
The functional excipients division has countless experienceand successful performance especially in pharmaceuticalindustry. It actively pursues development of new materialand technology.

High quality excipients for better
pharmaceutical drugs
Recent years see progress of studies how drugs can beabsorbed, distributed and show their effects in human body.
Based on these results, drug formulation technologies tailoredto the characteristics of the drugs have been pursued.
In line with this, role of pharmaceutical excipients has becomefurther clarified and their importance has increased.
Pharmaceutical excipients do not have their own medicinal
effect. Nevertheless pharmaceutical excipients play so much
important roles that they affect original purpose of drugs
depending on their selection.

Institute for Technology Development

3

Freund is conducting research and development of various
excipients in order to meet the current drug formulation needs
with the corporate philosophy of “Develop the Future byCreativity”.

4Pharmaceutical Excipients
DilactoseTM

GranutolTM

DilactoseTM is developed by our unique fluid bed granulation method. It isuseful as an excipient for direct compression. DilactoseTMF (Fine) is small
particle size grade DilactoseTM. In comparison with the existing grades, bothformability and disintegration have been improved.

GranutolTM is an excipient for the direct compression of D-Mannitol, using
an application of the DilactoseTM (directly compressible lactose) technology
cultivated by our company. We have 3 different types with different particle
sizes.

Line-upLine-up

We have 2 different types with different particle sizes.
TypeWe have 3 different types with different particle sizes.

Dilactose STM

Dilactose F (Filne)

Type

GranutolTM R

GranutolTM S

GranutolTM F (Fine)

Compendial

Lactose Hydrate JP
Lactose Monohydrate USP-NF, Ph. Eur.

Lactose Hydrate JP
Lactose Monohydrate USP-NF, Ph. Eur.

Compendial

D-Mannitol JP
Mannitol USP, Ph. Eur.

D-Mannitol JP
Mannitol USP, Ph. Eur.

D-Mannitol JP
Mannitol USP, Ph. Eur.

Particle size specification

355 μm on Not more than2%355~75 μm
50-70%
75 μm pass
30-50%

180 μm on Not more than2%
180~53 μm
50-80%
53 μm pass
20-50%

500 μm onNot more than
500~75 μm
Not less than
75 μm pass
Not more than

500 μm on
Not more than
2%
500~75 μm
Not less than
50%
75 μm pass 20~50%

250 μm on
Not more than2%
250~45 μm 40~80%
45 μm pass 20~60%

Physicalproperties

Particle
size
distribution
Bulk density

TM

D1051 μm

33 μm

D50

94 μm

64 μm

D90

169 μm124 μm0.55 g/mL

0.47 g/mL

38°

39°

Angle of reposexxParticle size specification

D10
Particle
size
D50
Physical distribution
D90
properties
Bulk density
Angle of repose

2%
80%
20%78 μm

41 μm

35 μm

154 μm

83 μm

65 μm

253 μm

147 μm137 μm0.53 g/mL

0.55 g/mL

0.49 g/mL

33˚39˚34 ˚SEM images
SEM images* Physical properties are representative values, not specifications.
* Physical properties are representative values, not specifications.

Features

5Tablet hardness(N)Excellent compression formability and fluidity
GranutolTM has good compression formability to avoid compression problems such as capping andsticking. It also has excellent fluidity for direct compressive excipient.
Suitable excipient for orally disintegrating and chewable tablets
D-Mannitol is moderately sweet and has
cool taste so that it has good dose
feeling. Combination with appropriate
volume of disintegrating agents provides
quickly disintegrating effect to tablets inthe mouth.
It has a finer particle grade
GranutolTM F, finer grade of GranutolTM, has
excellent disintegrating effect with thesame compression formability in comparison with spray dried mannitol.

Physical Properties of Granutol Tablets
Formulation

S, R : Granutol: Mg-St=100:1.0
F: Granutol: Mg-St=100:1.2

Tabletting

8mmφ -10R, 200 mg/Tab, Speed : 50 rpm

180160140120100F
S
R

80604046810 12 14Compression Pressure (kN)

500
Disintegration time (sec)Excellent Storage Stability
Absorbency is not as high as spray dry lactose so there is
extremely low potential for the occurrence of caking overtime.

FeaturesHardness (N)Excellent Mixability and Fluidity
Even though the particle size of DilactoseTM S is very finein order to enhance mixability with API, it has excellent
fluidity. This comes from the manufacturing process
because lactose crystals are all finely granulated.

Disintegration time(sec.)

Well-balanced between compression formability and disintegration
Lactose manufactured by high-shear granulation is generally inferior in compressive formulation.
On the other hand, lactose manufactured by the spray dry method has excellent compressive
formability but conversely tends to be inferior in disintegration. In comparison, DilactoseTM, which
is manufactured by the fluid bed granulation method, isexcellent on both counts so it is possible to obtain tabletswith high hardness and fast disintegration.

R400S

300200F

1000050100 150Hardness (N)2006Pharmaceutical ExcipientsNONPAREILTM

NONPAREILTM-105

High sphericity makes it possible to calculate volume and surface dimension and it is easy to control film thickness in controlled-release drugs.
Narrow particle size distribution When layering drugs, granules with sharp
particle size distribution can be obtained. In addition, the thickness of film
does not vary in the layering process and the speed of API release very
stable.

NONPAREILTM-105 is a spherical granule made from lactose and microcrystalline cellulose.

Line-up
GradeNONPAREIL®-108 (150)Line-upNONPAREILTM-105 (50-83)

NONPAREILTM has 3 different types of composition and it is possible toselect a type according to API interaction or usage. There are following
grades with different particle sizes.
TypeNONPAREILTM-103

NONPAREILTM-105

Ingredients

Purified sucrose

Compendial

Purified Sucrose Spheres
JPE(US DMF registered)

LactoseMicrocrystalline cellulose
Lactose.Microcrystalline
Cellulose Spheres JPE(US DMF registered)

Grade(particle size)

20-24 (850-710 μm)
24-32 (710-500 μm)
32-42 (500-355 μm)

50-83 (300-180 μm)
150 (212-106 μm)

ASTM

Loss on drying
Bulk density

NONPAREILTM-108

50-83

150

300-18050-80

212-106
70-140Not more than
5.0%

Not more than
5.0%

0.76 g/mL

0.73 g/mL

Angle of repose

31°

33°

Friability

0.29%

0.18%

* Physical properties are representative values, not specifications.

D-MannitolFeatures

D-Mannitol JP
Mannitol USP, Ph. Eur.
(US DMF registered)High Mechanical Strength
As granule hardness is high and has excellent wear-resistance, there is little
damage during granulating/coating process and it makes handling easier.

32-42 (500-355 μm)
200 (250-150 μm)
100 (150-75 μm)

Sugar Free Composition
Low reactivity with API and low in calories.

NONPAREILTM-103

Low Cohesiveness
Blocking hardly occurs during storage.

NONPAREILTM-103 is a spherical granule consists of purified sucrose.

NONPAREILTM-108

GradeParticle size

20-24

24-32

32-42

Microns

850-710710-500

500-355

ASTM

20-25

25-35

35-45

Not more than
0.20%

Not more than
0.20%

Not more than
0.20%

Loss on drying
Physicalpropertie

Bulk density

0.88 g/mL

0.87 g/mL

NONPAREILTM-108 is a spherical granule made from D-Mannitol.

Line-up
GradeParticle size

0.86 g/mL

Angle of repose

30°

30°

32°

Friability

0.40%

0.20%

0.04%

* Physical properties are representative values, not specifications.

Features100% Purified sucrose
Granule hardness is high and has excellent wear-resistance.
It is completely soluble in water.
Low Free Water (less than 0.1%)
It has very little influence on the stability of API that are interactive with water.
Perfect for Powder Layering
By the high solubility of sucrose in water, layering effectively progresses
with a low binder quantity.

7Particle size

Physicalpropertie

Line-upNONPAREILTM-103 (32-42)

Microns

NONPAREILTM-108 (200)

Microns
ASTM

Loss on drying
Physicalpropertie

Bulk density

32-42

200

100

500-355

250-150

150-7535-45

60-100100-200

Not more than
0.5%

Not more than
0.5%

Not more than
0.5%

0.77 g/mL

0.72 g/mL

0.72 g/mL

Angle of repose

31°

33°

37°

Friability

0.28%

0.12%

0.31%

* Physical properties are representative values, not specifications.

FeaturesD-mannitol 100%
Chemically stable and low interaction with API due to less free water.
It is soluble in water completely.
Small particle size grades are available
100 and 200 grades are effective for capsule miniaturizing, and for ensuring
uniformity of minute amounts of API.
Especially 100 grade is most appropriate for core particle for OD tablets.

8Pharmaceutical Excipients
Titanium Oxide FG

AdsoliderTM-101

Titanium Dioxide is widely used to protect the colouring of granules,
tablets, capsules and API from light. Our high purity titanium oxide
has excellent dispersiveness.

AdsoliderTM-101 is a fine powder of silicon dioxide manufactured by theliquid phase method, consisting of high purity silica sand as its rawmaterial.
Compared to products manufactured with the vapor phase method,
AdsoliderTM-101 is rich in porosity with large interior specific surface area.
TypeType
Compendial
Mean diameter

Titanium Oxide FG
Titanium Oxide JP
Titanium Dioxide USP, Ph.Eur.
Brightness (dispersion liquidof FG 10 g /water 3.5 mL)

0.55 μm

Compendial
Mean diameter (μm)
Loss on drying (%)
Volume of oil absorption (mL/100g)
pH
Volume test (mL/5g)
Specific surface area (m²/g)

87* Physical properties are representative values, not specifications.

AdsoliderTM-101
Light Anhydrous Silicic Acid JP
Silicon Dioxde USP-NF
Colloidal Hydrated Silica Ph.Eur.
3.2
2.63107.690300* Physical properties are representative values, not specifications.

SEM imageFeatures
High concealment
Concealing original color by coloring and whitening for tablets and capsules.
Excellent Light-proofing
Protects sensitive API from UV rays and improves stability.
Excellent Dispersiveness in water

Usage Method
This product is usually used by dispersing in water with a homogenizer andadding film or sugar coating liquid.

FeaturesExcellent effects in improving fluidity.
In many formulations, adding 0.1 - 0.5% of AdsoliderTM improved fluidity.
The optimum volume to be added differs depending on the property ofmixed powder.
Pill solidity and tablet hardness improves by adding AdsoliderTM.
With addition of AdsoliderTM, the hardness of tablet improves by 5-15%
without losing disintegration.
Compression
pressure

Adding volume

10 kN

0%
0.4%

AdsoliderTM-101
Tablet hardness(N) Disintegration time(sec)
54.7
34
58.830* Tablet formulation: Dilactose® S (granulated lactose)/corn starch/microcrystalline cellulose/acetaminophen/Mg-St

Suitable for the powderization of liquids.
Adding 0.5-2 AdsoliderTM-101 to 1 liquid-type API makes easypowderization.
The pH of AdsoliderTM-101 is around neutrality (6.0– 8.0). It is lessinteractive with API.

910

Pharmaceutical Excipients
LubriwaxTM-101

CMECTM

It is suitable as a lubricant or a wax matrix former.

CMECTM (Carboxymethylethylcellulose) contains cellulose as a raw materialand is mixed ether that is obtained by carboxymethylation and ethylation.
Listed in JPE and this is mainly used as a base for enteric film coating andcontrolled-release formulation. In addition, it can be used as a carrier forsolid dispersion with the aim of improving the solubility of poorly solubledrugs.

TypeLubriwaxTM-101
Hydrogenated Oil JP
Hydrogenated Caster Oil
USP-NF, Ph.Eur.

Compendial
Physical propertie

Mean diameter
22 μm

Bulk density
0.36 g/mL

Melting point
86℃* Physical properties are representative values, not specifications.

FeaturesFeatures
The standard additive volume of LubriwaxTM-101 : 0.5 to 5%
Less interaction with API
As it does not contain metal components such as calcium and magnesiumor free acids, there are less influences on API stability.
Less influence on tablet hardness
The hardness is less influenced when added to and mixed with tabletpowder.

In addition, the combination with controlled release base of pH
independency enables forming various dissolution patterns.

LubriwaxTM-101

400Matrix-Forming Material
CMECTM is also used for a matrix-forming material with API. By changing
the ratio of API and CMECTM, it can control releasing speed.

Magnesium stearate

05101520Mixing time for V-type mixer(min)Polishing waxTM-105
Polishing waxTM-105 is a finely powdered Carnauba Wax and it complies withJP, USP-NF, Ph. Eur.
Carnauba wax has the highest melting point among all vegetable-based
waxes and it forms glossy layer of shiny membrane so that it is particularly
suitable for polishing surface of tablets.

Features
Type

Polishing waxTM-105
Carnauba Wax JP
USP-NF, Ph.Eur.

Compendial
Physical propertie

Mean diameter Angle of repose
14 μm

45°

Bulk density
loose
tap
0.51 g/ｍL
0.25 g/mL* Physical properties are representative values, not specifications.

Improve dissolution of poorly soluble drugs
CMECTM is a carrier of solid dispersion for improving solubility of poorlysoluble API.
Protective coating for sugar-coated tablet
CMECTM is effective as protective coating agent, for tablets containing
water-sensitive API by moisture prevention effect with apprx. 100µmthickness.
120100
Disintegration time(min)20Agent for enteric and controlled release
The disintegration behavior of tablet coated with CMECTM depends on pHand independent from buffer solution type. Low pH gives slow
disintegration and high pH gives fast disintegration.
CMECTM is suitable as an enteric base through controlled-release drugs.

60
Tablet hardness(N)Influence on hardness by mixing timeis minimalHigh chemical stability
Consisting of ether linkage, it is chemically stable and hydrolysis hardly
occurs.

80
60
40
2005

67

8

pH of buffer solution
Clark-Labs buffer

Mcilvaine buffer

Polishing waxTM forms glossy surface on sugar coated and filmcoatedtablets.
It improves tablets smoothness and handling.

1112FREUND Pharmaceutical Excipients Product Table
Trade Name

Grade

CompendialComponents

Appearance

Packing Unit

Conventional
TabletODT
MUPS

HardCapsule

GranuleFine GranulePowderMain Applications

For Pharmaceutical
DilactoseTM

S

30kg plastic drum
Lactose Hydrate JP
Lactose Monohydrate
USP-NF, Ph.Eur.

DilactoseTM

F

GranutolTM

R

GranutolTM

S

GranutolTM

F

Lactose Hydrate100%

White granulated powder

Directly Compressible Lactose
20kg carton

D-Mannitol JP
Mannitol USP, Ph. Eur.

D-Manitol 100％

White granulated powder

20kg carton

Directly Compressible Mannitol

NONPAREILTM-103

20-24
24-32
32-42

Purified Sucrose Spheres JPE(US DMF registered)

Sucrose100%

White spheres20kg carton

NONPAREILTM-105

50-83
150

Lactose・Microcrystalline
Cellulose Spheres JPE(US DMF registered)

Lactose Hydrate
60.0〜80.0%
Microcrystalline Cellulose
40.0〜20.0%

White to pale yellowish
white spheres20kg carton

D-Mannitol JP
Manitol USP, Ph.Eur.
(US DMF registered)

D-Manitol 100％

White spheres20kg carton

Titanium Oxide JP
Titanium Dioxide USP, Ph.Eur.

Titanium Dioxide

White powder

25kg carton

Coloring agent

5kg kraft paper bag

Absorbent
Glidant

32-42

NONPAREIL -108
TMTitanium Oxide FG

AdsoliderTM-101

200100Light Anhydrous Silicic Acid JPSilicon Dioxide USP-NF

Silicon Dioxidelight, fine powder

Colloidal Hydrated Silica Ph.Eur.

LubriwaxTM-101

Polishing waxTM-105

CMECTM

Hydrogenated Oil JP
Hydrogenated Castor Oil
USP-NF Ph.Eur.

HydrogenatedCastor Oil

White powder

20kg kraft paper bag

LubricantSustained release baseCarnauba Wax

White to light yellow
powder

5kg carton

Gloss agent

Carboxymethylethyl
cellulose

White to yellowish
white powder or granules

10kg carton

Solid Dispersion
Enteric film coating and controlled
release agent

Carnauba Wax JP
Carnauba Wax USP-NF Ph.Eur.

Carboxymethylethyl
cellulose JPE

White to bluish white,

Spherical core for enteric corting
Sustained release granules◎ most suitable13〇 suitable
14