Professional Documents
Culture Documents
Avicel PH Microcrystalline Cellulose, NF, PH Eur., JP, BP: Section 11
Avicel PH Microcrystalline Cellulose, NF, PH Eur., JP, BP: Section 11
Table of Contents
Avicel Microcrystalline Cellulose............................................................................................................1
Table of Contents...............................................................................................................................1
Manufacturing Process ..........................................................................................................................2
Importance of the Commercial Introduction of Avicel PH Microcrystalline Cellulose to
Direct Compression ...........................................................................................................................4
The Tableting Characteristics of Avicel Microcrystalline Cellulose........................................................5
A Comparison of Avicel Microcrystalline Cellulose
Types and their Uses .........................................................................................................................7
Figure 3: PH-101...............................................................................................................................7
Figure 4: PH-102...............................................................................................................................8
Figure 5: PH-103...............................................................................................................................8
Figure 6: PH-105...............................................................................................................................9
Figure 7: PH-112...............................................................................................................................9
Figure 8: PH-113.............................................................................................................................10
Figure 9: PH-200.............................................................................................................................10
Figure 10: PH-301...........................................................................................................................11
Figure 11: PH-302...........................................................................................................................11
Avicel PH Microcrystalline Cellulose Functionality in the Wet Granulation Manufacturing Process ...12
Rapid, Even Wicking Action ............................................................................................................12
Controls Wet Mass Consistency......................................................................................................12
Less Screen Blocking ......................................................................................................................12
Uniform, Rapid Drying .....................................................................................................................12
Controls Color Mottling and Drug Content Uniformity ....................................................................12
Acts as an Auxiliary Binder ..............................................................................................................13
Avicel PH Microcrystalline Cellulose as a Spheronizing Agent ...........................................................13
Editors Note.........................................................................................................................................14
Bibliography/Publications ....................................................................................................................15
Manufacturing Process
In 1962, O. A. Battista and P. A. Smith
reported the preparation by the American
Viscose Company of microcrystalline cellulose from cellulose, hence the origin of the
product name Avicel. The PH designation indicates that the product is suitable
for pharmaceutical use. Cellulose is present
in much of the food of man but is inert to
human digestive enzymes making it GRAS
or generally recognized as safe for human
consumption by the United States Food
and Drug Administration (FDA) and other
governmental agencies throughout the
world. The process that produces Avicel PH
microcrystalline cellulose alters only the
cellulose physical form and eliminates
impurities. Avicel remains alpha-cellulose,
the most abundant of all organic materials,
in a highly purified powder form.
Microcrystalline cellulose is the subject
of harmonized monographs in the NF, the
European Pharmacopoeia and the Japanese
Pharmacopoeia.
If a food grade sodium carboxymethylcellulose is added to the microcrystalline cellulose, with additional wet attrition before
drying, a colloidal microcrystalline cellulose
is produced (Avicel RC/CL) which can
function as a suspending agent, emulsion
stabilizer, etc. A schematic diagram of the
PH and RC/CL manufacturing processes
is shown in Figure 1.
Dicer
Pulp
Reactor
PH
RC/CL
Filter
Na CMC
Mix
Tank
Mixer
Spray
Dryer
Drying and
Subsequent
Processing
Storage
and
Packaging
Storage
and
Packaging
Cellulose
Chemical
Derivatization
Mechanical
Disintegration
Chemical
Depolymerization
Wet Mechanical
Disintegration
Soluble
Cellulose Derivative
Fibrous
Cellulose Floc
Drying
Dispersing
Agent
+ Water
Hydrocolloid
Solution
Microcrystalline Cellulose
Powder
Colloidal
Microcrystalline Cellulose
+ Water
Aqueous Colloid
will carry most direct compression formulations, although there have been individual
applications where less (10%) was sufficient or more (50%) was necessary.
When placed in water, a pure microcrystalline cellulose tablet swells and disintegrates. While microcrystalline cellulose is not
as efficient a disintegrant on a gram for gram
basis compared to disintegrants such as
corn starch, the swelling that it exhibits has
been utilized in some formulations for disintegrant purposes. This swelling and disintegration has been attributed to penetration
of water into the cellulose matrix as a result
of pore capillary action with subsequent
disruption of the hydrogen bonds holding
the fibrils together. Swelling and disintegration is not observed in non-polar liquids.
The hydrogen bonding which holds microcrystalline cellulose compacts together contributes to the appearance and effectiveness
of a film coating regardless of whether it is
applied from an aqueous or organic system.
Free hydroxyl groups are present on the surface of the core tablet, which provide excellent binding sites for cellulosic films. Film
adhesion and tensile strength are increased
Figure 3: PH-101 Most widely used for direct compression tableting, wet granulation and
spheronization; also used in capsule filling processes, especially those employing tamping or
other means of consolidation as part of the process.
Figure 4: PH-102 Used as above but larger particle size improves flow of fine powders.
Figure 5: PH-103 Same particle size as PH-101; reduced moisture content (3%); used
where moisture sensitive pharmaceutical active ingredients are present.
Figure 6: PH-105 Smallest particle size; most compressible of the PH products; useful in
direct compression of coarse, granular, or crystalline materials; can be mixed with PH-101 or
PH-102 to achieve specific flow and compression characteristics; has applications in roller
compaction; poorly flowable by itself cannot determine neat compressibility.
Figure 7: PH-112 Same particle size as PH-102; much reduced moisture content (1.5%);
used where very moisture sensitive pharmaceutical active ingredients are present.
Figure 8: PH-113 Same particle size as PH-101; much reduced moisture content (1.5%);
used where very moisture sensitive pharmaceutical active ingredients are present.
Figure 9: PH-200 Large particle size with increased flowability; used to reduce weight
variation and to improve content uniformity in direct compression formulations and (as a
final mix additive) in wet granulation formulations.
10
Figure 10: PH-301 Same particle size as PH-101 but more dense providing increased
flowability, greater tablet weight uniformity, the potential for making smaller tablets, and
improved mixability; useful as a capsule filling excipient.
Figure 11: PH-302 Same particle size as PH-102 but more dense providing increased
flowability, greater tablet weight uniformity, the potential for making smaller tablets, and
improved mixability; useful as a capsule filling excipient.
11
12
as noted above. Having a uniform distribution within the dried granule will result in
tablets, after dry milling of the granules, final
mixing and compression that are uniform in
surface appearance and drug content. The
possibility of losing large amounts of active
ingredient to the dust collection system in
the fines which are generated during the
milling process as the granules first break,
is virtually eliminated, since the active
ingredient is uniformly distributed throughout
the granule and not concentrated on the
surface. This source of possible analytical
deviation from theoretical values is no
longer a concern.
Editors Note
Dr. George E. Reier died Tuesday, August 3. 1999, after a prolonged illness. He was a
retired Senior Pharmaceutical Associate of the pharmaceutical business, FMC BioPolymer.
George was a graduate student of Dr. Ralph F. Shangraw at the University of Maryland
School of Pharmacy. His and other graduate students research in the early 1960s resulted
in the first papers to appear in the scientific literature on the use of microcrystalline cellulose
in tableting. Despite his illness, he worked diligently to complete this chapter on MCC
a tribute to his work ethic and his love of pharmaceutlcal research.
Dr. Reier was a gentleman in the true sense of the word and a stellar scientist by any
measure. He was a gentleman with all the positive attributes of class, e.g., integrity,
compassion, a sense of fairness, plus a quality of graciousness in manner, speech, style
and image. George was modest and funny and self-deprecating and charitable to those
he knew, as well as to strangers. He always had a smile. He was a source of knowledge
and wisdom for all of us within FMC BioPolymer. We will miss his advice and counsel.
I will miss George.
Thomas A. Wheatley, Technical Editor
14
Bibliography/Publications
The references presented herein are not
intended to be all-inclusive for microcrystalline cellulose. They are intended to
provide a useful list of references for the
reader who wishes to learn more or to study
in greater detail the properties and applications of Avicel PH Microcrystalline
Cellulose. In some cases, references have
been included that are not specific to the
use of microcrystalline cellulose in tablets
so that the reader might supplement his/her
understanding of the applications of this
material. For copies of these publications,
please contact your local library or information services department.
15
16
17
49. Cid, E., Jaminet, F., Influence of adjuvants on the rate of dissolution and the
stability of acetylsalicylic acid in tablets,
J. Pharm. Belg., Vol. 26, (1), p. 38, 1971.
62. Marshall, K., Sixsmith, D., Some physical characteristics of microcrystalline cellulose, Drug Development Communications,
Vol. 1, (1), p. 51, 1974-1975.
18
19
96. Rowe, R.C., The adhesion of film coatings to tablet surfacesthe effect of some
direct compression excipients and lubricants, Journal of Pharm. Pharmacol., Vol.
29, (12), p. 723, 1977.
20
21
22
23
24
160. Van der Watt, J.G., Effect of the particle size of microcrystalline cellulose on tablet
properties in mixtures with magnesium
stearate, Int. J. Pharm., Vol. 36, (1), p. 51,
1987.
25
p. 643, 1995.
26
27