Lactose Intolerance

Lactose intolerance is the inability to digest lactose, a sugar in milk

and milk product. Lactose intolerance results from -galactosidase
(lactase) deficiency. Lactase is the enzyme necessary to metabolize
lactose. Lactose intolerance can lead to excess gas, cramping,
diarrhea, or severe allergic reaction. It is estimated that 55% of
Northern Europeans, 95% of North Americans, 90% of Asians are
lactose intolerant.
Lactose is still a commonly used excipient in pharmaceutical and
nutraceutical formulations. Alternative excipient choices prevent
the need for using lactose in tablets. Alternative excipients, such as
, or , Dibasic Calcium
Phosphate (DCP)
ARBOCEL EMCOMPRESS

Powdered Cellulose
are available.
Issue II/2006
Content page
Lactose Intolerance 1
About Cellulose 1
A Little Chemistry 2
Cellulose for Pharmaceutical Use 2
Types of 3
Applictions of 3
Versus Lactose in
Direct Compression Formulations 3-4
as a Filler in
Combination with 4
in a
Classical Wet Granulation 4
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ARBOCEL
ARBOCEL
ARBOCEL P 290
ARBOCEL P 290
VIVAPUR 12
ARBOCEL P 290

Technical
Newsletter
Page 1
Info-Hotline: + 49 (0) 79 67 / 1 52-312
ARBOCEL
ARBOCEL
ARBOCEL
ARBOCEL

is a classical excipient for pharmaceutical

formulations, which became more and more popular during the
last years. is from derived Cellulose, a renewable
source from nature .
Powdered cellulose is inert and is not metabolized by the human
body. Since it is not digested, it has no functional caloric value.
is used by formulators as an alternative to lactose.
the
lactose intolerant population continues to increase, which makes
lactose less desirable for formulation development.
1
is plant derived and no BSE/TSE risk will occur, which
had been an issue in Europe some years ago. Additionally,
ARBOCEL

Powdered Cellulose, Ph.Eur., USP/NF, JP

About Cellulose
Powdered cellulose is from
renewable sources.
Cellulose is the most common
organic substance on earth. It
is part of nearly all plants and
some microorganisms. In our
daily life we find cellulose in
paper, packaging materials, hy-
gienic articles, and of course in
all plant derived food, for exam-
ple fruits and vegetables. Cellu-
lose is found in many pharma-
ceutical solid dosage forms as
binder or filler.
Trees are the primary cellulose source. So the raw material for our
powdered cellolose or microcrystalline comes from different wood
sources.
1
For the production of the cleaned cellulose is milled, sieved and
adjusted to a special particle size. This cellulose is called .
ARBOCEL

Powdered Cellulose
Technical
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Page 2
Issue II/2006
Info-Hotline: + 49 (0) 79 67 / 1 52-312
Fig. 2 : C C C U ellulose hain, omposed from -Glucose nits
Cellulose for Pharmaceutical Use
As mentioned above, the cellulose is primarily used for pharma-
ceuticals.
Native cellulose shows two different areas, crystalline and amor-
phous. The crystalline region is an area where the cellulose chains
are ordered. In the amorphous region the cellulose chains are
randomly ordered.
As a pharmaceutical excipient, two types of cellulose are in use,
powdered and microcrystalline. Both are derived from raw
cellulose.
During microcrystalline cellulose manufacture, most of the amor-
phous area is removed. Powdered cellulose is not chemically modified,
so amorphous material remains. During powdered cellulose manu-
facture, the raw cellulose is washed, milled, sieved and adjusted
to a specific particle size distribution.
a-
Table 1
Powdered Cellulose 45 % crystalline 55 % amorph
Microcrystalline Cellulose 70 % crystalline 30 % amorph
crystalline
region
am
orphous
region
Fig. 3 : Single Fiber
HO
H
O
HO
H
H
H
O
O
OH
H
H
HO
O
H
H
H
OH
O
H
OH
O
HO
H
H
O
HO
H
O
H
O
H
H
H
O
O
OH
H
H
HO
O
H
H
H
OH
O
H
OH
O
HO
H
O
HO
H
O
H
O
H
H
H
O
O
OH
H
H
HO
O
H
H
H
OH
O
H
OH
O
HO
H
O
HO
HO
OH
OH
OH
O
H
H
H
H
C
H
2
C
C
C
C
C
H
Fig. 1 : -Glucose, the Unit for the Cellulose Chain
A Little Chemistry
bonds with each other, holding the chains firmly together and con-
tributing to their high tensile strength (Figure 2). Given a cellulose
material, the portion that does not dissolve in a 17.5% solution of
sodium hydroxide at 20 C is cellulose, which is true cellulose,
primarily used for pharmaceuticals; the portion that dissolves and
then precipitates upon acidification is -cellulose; and the portion
that dissolves but does not precipitate is -cellulose. For humans
this material is absolutely inert, not absorbable and noncaloric.
Additionally, the cellulose is not a good medium for
microorganisms which decreases the risk of microbial spoilage.
a
g
-
Cellulose (C H O )n is a long-chain polymeric polysaccharide carbo-
hydrate, of monomers
1 > 4 glycosidic bonds by conden-
sation. This forms a straight chain polymer which molecule adopts
an extended rod-like conformation. The degree of polymerization
gives the average number of the residues in the chain. In microfibrils,
the multiple hydroxyl groups on the glucose residues form hydrogen
6 10 5
-glucose (Figure 1). Cellulose ( -glucose)
are linked together through
Info-Hotline: + 49 (0) 79 67 / 1 52-312
Technical
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Issue II/2006
Types of ARBOCEL

Table 2
Form Powder Powder Granulate
Particle Size 60 m 80 m 150 m
Bulk Density 0,22,g/ml 0,30 g/ml 0,35 g/ml
Angle of Repose 62 49 36
M 80 P 290 A 300
JRS supplies two types of powder and a granulated material
(Table 2). Type M 80 is designed for wet granulation. P 290
can be used for direct compression in combination with other
binders, e.g. , or
. The A 300 with a particle size of 150 m is
recommended for capsule filling due to improved flow.
VIVAPUR 102
VIVAPUR 12

Microcrystalline Cellulose
The differences between the powder and the granulated material
can be seen in the SEM pictures. Both, the M 80 (Figure 4) and
the P 290 (Figure 5) have a fine, fibrous structure, while the
Fig. 5 : ARBOCEL P 290

Fig. 6 : ARBOCEL A 300

The compression profile shows the compressibility of the 3

types. The M 80 and P 290 provide more robust tablets
than A 300, which is recommended for capsule filling (Figure 7).
ARBOCEL

Applications of ARBOCEL

0 25
180
160
140
120
100
80
60
40
20
0
5 10 15 20
H
a
r
d
n
e
s
s
[
N
]
Compression Force [kN]
Fig. 7 : Compression Diagram of the 3 Grades. ARBOCEL

ARBOCEL P 290
ARBOCEL A 300
ARBOCEL M 80

ARBOCEL P 290

Versus Lactose in Direct Compression Formulations

Table 3 : Parameters of Placebo Tablets Compressed with Lactose DC or resp. ARBOCEL

Compressibility of Powered Cellulose

ARBOCEL
EMCOMPRESS

49.5
50.0 %
Magnesium Stearat 0.5 %
Powdered Cellulose
CalciumHydrogen Phosphate
A comparison between tablets compressed from a MCC / lactose
blend vs. tablets compressed from a MCC / powdered cellulose
blend (Table 3). There is no significant difference in tablet proper-
ties, which infers that lactose can be substituted by cellulose with-
out issue.
A 300 (Figure 6) is compacted to larger, sometimes round shaped
particles. It is obvious that P 290 has more binding properties and
A 300 shows better flowability.
50 % 50 %
50 % Lactose DC 50 %
VIVAPUR 102 VIVAPUR 102
ARBOCEL P290

(Microcrystalline Cellulose) (Microcrystalline Cellulose)

(Powdered Cellulose)
Compression Force 6,0 kN 6,0 kN
Hardness 6,9 kp 6,8 kp
Tablet Weight 436 mg 423 mg
Rel.stand.dev 2,1 % 2,3 %
Fig. 4 : ARBOCEL M 80

Technical
Newsletter
Page 4
WORLDWIDE HEADQUARTERS USA+Canada
JRS PHARMA GMBH+CO.KG JRS PHARMA LP, USA
JRS PHARMA
LEADING
THE WORLD
IN EXCIPIENTS
A Member of the JRS Group
2981 Route 22, Suite 1
Patterson, NY 12563-2359
Toll-Free: (800) 431-2457
Phone: (845) 878-3414
Fax: (845) 878-3484
E-mail: info@jrspharma.com
www.jrspharma.com, www.jrs.de
Holzmhle 1
D-73494 Rosenberg (Germany)
Phone: + 49 (0) 79 67 / 1 52-0
Fax: + 49 (0) 79 67 / 1 52-345
E-mail: info@jrspharma.de
www.jrspharma.de,
www.jrs.de
Customer Service: Customer Service: ++49 (0) 7967 / 152-312 (845) 878 3414
Issue II/2006
Table 5: Ambroxol Formulation with ARBOCEL P 290

Table 4 : Ascorbic Acid Formulation Where Lactose is Replaced by ARBOCEL P 290

Ambroxol HCl 30.0 mg 20.0 %

69 3 mg 46 2 %
46 2 mg 30 8 %
3 0 mg 2 0 %
1 5 mg 1 0 %
Tablet Weight 150 mg
Diameter 8 mm
Compression Force 12.5 kN
Hardness 6.4 kp
Disintegration Time 15 sec
VIVAPUR 12 . .
ARBOCEL P 290 . .
VIVASOL . .
PRUV . .

(Microcrystalline Cellulose)
(Powdered Cellulose)
(Croscarmellose Sodium)
(Sodium Stearyl Fumarate)
Table 6: Piroxicam Formulation with ARBOCEL P 290

Way of preparation : Piroxicam, and

were granulated using an 20% ethanolic povidone solution.
, Aerosil and magnesium stearate were then added and
mixed for 5 minutes. The blend was compressed at a compaction
force of about 17.5 kN (Table 6).
VIVAPUR 101 ARBOCEL P 290
VIVASOL

ARBOCEL P 290

in a Classical
Wet Granulation
A formulation with as a plant-derived filler is shown
(Table 5). provides the hardness and the flowability.
adds to the hardness as well.
ARBOCEL P 290
VIVAPUR 12
ARBOCEL

ARBOCEL P 290
VIVAPUR 12

as a Filler in
Combination with
In an ascorbic acid formulation, the lactose was replaced by
(Table 4). Hardness vs. compression force is the same in both
tablets formulations. This indicates that can be used
as an alternativ to lactose. The lactose-free version demonstrates
better disintegration time.
ARBOCEL
P 290
ARBOCEL P 290

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.
ARBOCEL P 290

Versus Lactose in Direct

Compression Formulations
Ascorbic Acid 50.0 % 50.0 %
24 5 % 24 5 %
24 5 %
Lactose 24.5 %
Magnesiumstearate 1.0 % 1.0 %
Tablet Weight 200 mg 200 mg
Diameter 10 mm 10 mm
Compression Force 11.0 kN 11.4 kN
Hardness 10.8 kp 10.7 kp
Disintegration Time 50 sec 62 sec
VIVAPUR 102 . .
ARBOCEL P 290 .

(Microcrystalline Cellulose)
(Powdered Cellulose)
Piroxicam 10.00 mg 6.7 %
76 80 mg 51.2 %
51 20 mg 34.1 %
3.00 mg 2.0 %
PVP Kollidon 25 7.50 mg 5.0 %
Magnesium Stearate 0.75 mg 0.5 %
Fumed Silica 0.75 mg 0.5 %
Tablet Weight 150 mg
Diameter 8 mm
Compression Force 17.5 kN
Hardness 5.8 kp
Disintegration Time 39 sec
VIVAPUR 101 .
ARBOCEL P 290 .
VIVASOL

(Microcrystalline Cellulose)
(Powdered Cellulose)
(Croscarmellose Sodium)
4
2
9
1
E
3
.
0
0
6
0
9
K
E