COMILLA UNIVERSITY

Department Of Pharmacy

Assignment On : Compaction and compression of powder (Bonding to

tablets, the effect of compressional force on tablet
properties)
Course Title : Pharmaceutics-II
Course Code : PHARM- 3201

Submitted To :
Rafeza Khatun
Lecturer
Department Of Pharmacy
Comilla University

Submitted By :
Md. Jabedul Alam Sarkar
ID : 11715017
Session : 2016-17
Group No. : 02
Department Of Pharmacy
Comilla University

Date Of Submission : 02-01-2020

 INDEX
Serial Topics Name Page
No. No.
1. Introduction 1
2. Advantages of the tablet dosage form 3
3. Disadvantages of tablet dosage form 3
4. General properties of tablet dosage form 4
5. Compaction of pharmaceutical powders 5
6. Characterisation of compaction behaviour 5
7. Compression forces 7
8. Bonding to tablets 7
9. Types of bonding in tablets 8
10. Properties of tablet 11
11. The effect of compressional force on tablet properties 11
12. Conclusion 17
13. References 19
 COMPACTION AND COMPRESSION OF
POWDER
(BINDING TO TABLETS, THE EFFECT OF COMPRESSIONAL FORCE
ON TABLET PROPERTIES)
INTRODUCTION :

Oral dosage forms are the most common methods of drug delivery. Among
the oral dosage forms tablets and capsules are predominantly used.
Tablets are widely used and are more popular as compared to capsules.
Tablets are defined as the solid unit dosage forms containing medicaments
with or without excipients such as binders, diluents, lubricants etc. and
prepared either by molding or compression. According to the Indian
Pharmacopoeia, “Pharmaceutical tablets are solid, flat or biconvex dishes,
unit dosage form prepared by compressing a drugs or a mixture of drugs,
with or without diluents. They vary in shape and differ greatly in size and
weight, depending on amount of medicinal substances and the intended
mode of administration”. It is the most popular dosage form and 70% of the
total medicines are dispensed in the form of Tablet. All medicaments are
available in the Tablet form except where it is difficult to formulate or
administer. Release of drug from the tablet can be controlled by altering the
design and content of the formulation. Also, since this is a dry dosage form,
tablets provide a supportive environment for drug stability and generally
have a relatively long shelf life. Tablets are manufactured by applying
pressure to a powder bed, which compresses the powder into a coherent
compact. The powder may consist of either primary particles or aggregated
primary particles (i.e. granules). When these are compressed, bonds are
established between the particles or granules, thus conferring a certain
mechanical strength to the compact.

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The properties of the tablet (e.g. mechanical strength, disintegration time
and drug release characteristics) are affected by both the properties of the
constituent materials and the manufacturing process. Excipients such as
diluents, binders and lubricants are generally needed in a formulation in
order to facilitate the manufacturing process, but also to ensure that the
resulting tablets have the desired properties. For instance, tablets should
be sufficiently strong to withstand handling during manufacturing and
usage, but should also disintegrate and release the drug in a predictable
and reproducible manner. It is thus important to choose the appropriate
excipient and manufacturing process when developing a new tablet
formulation.

The vast majority of all tablets manufactured today are made by

compression, and compressed tablets are the most widely used dosage
form. Compressed tablets are prepared by the application of high
pressures, utilizing steel punches and dies, to powders or granulations.
Recently, punching of laminated sheets, electronic deposition methods,
and three-dimensional printing methods have been used to make tablets.
Tablets have been in widespread use, since the latter part of the 19th
century, and their popularity continues. The term “compressed tablet” is
believed to have been first used by John Wyeth and Brother, Inc. of
Philadelphia. During this same period, molded tablets were introduced for
use as hypodermic tablets, for the extemporaneous preparation of solutions
for injection. Tablets remain popular as a dosage form, due to the
advantages afforded both to the manufacturer and to the patient. Although
the basic mechanical approach for most tablet manufacture has remained

2
the same, tablet technology has undergone great improvement and
experimentation.

ADVANTAGES OF THE TABLET DOSAGE FORM :

i) They are unit dosage form and offer the greatest capabilities of all
oral dosage form for the greatest dose precision and the least
content variability.
ii) Cost is lowest of all oral dosage form.
iii) Lighter and compact.
iv) Easiest and cheapest to package and strip.
v) Easy to swallowing with least tendency for hang‐up.
vi) Sustained release product is possible by enteric coating.
vii) Objectionable odour and bitter taste can be masked by coating
technique.
viii) Suitable for large scale production.
ix) Greatest chemical and microbial stability over all oral dosage form.
x) Product identification is easy and rapid requiring no additional
steps when employing an embossed and/or monogrammed punch
face.

DISADVANTAGES OF TABLET DOSAGE FORM :

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 i) Difficult to swallow in case of children and unconscious patients.
ii) Some drugs resist compression into dense compacts, owing to
amorphous nature, low density character.
iii) Drugs with poor wetting, slow dissolution properties, optimum
absorption high in GIT may be difficult to formulate or manufacture
as a tablet that will still provide adequate or full drug bioavailability.
iv) Bitter testing drugs, drugs with an objectionable odor or drugs that
are sensitive to oxygen may require encapsulation or coating. In
such cases, capsule may offer the best and lowest cost.

GENERAL PROPERTIES OF TABLET DOSAGE FORM:

i) A tablet should have elegant product identity while free of defects

like chips, cracks, discoloration, and contamination.
ii) Should have sufficient strength to withstand mechanical shock
during its production packaging, shipping and dispensing.
iii) Should have the chemical and physical stability to maintain its
physical attributes over the time.
iv) The tablet must be able to release the medicinal agents in a
predictable and reproducible manner.
v) Must have a chemical stability over time so as not to follow
alteration of the medicinal agents.

4
COMPACTION OF PHARMACEUTICAL POWDERS :

When pressure is applied to a powder bed, the bulk volume of the powder
is reduced and the amount of air is decreased. During this process, energy
is consumed. As the particles are moved into closer proximity to each other
during the volume reduction process, bonds may be established between
the particles.

The formation of bonds is associated with a reduction in the energy of the

system as energy is released (Coffin-Beach and Hollenbeck, 1983;
Rowlings et al., 1995). In the literature, the term compression is often used
to describe the process of volume reduction and the term compaction is
used to describe the whole process, including the subsequent
establishment of bonds. The strength of a tablet composed of a certain
material can be used as a measure of the compactibility of that material.
Volume reduction takes place by various mechanisms and different types
of bonds may be established between the particles depending on the
pressure applied and the properties of the powder.

CHARACTERISATION OF COMPACTION BEHAVIOUR :

-Deformation properties
5
Tablets were compressed at a maximum pressure of 150 MPa (papers II
and III) or 200 MPa (papers I and V) and the deformability of the materials
was characterised by recording the height of the tablets every millisecond
during the compression cycle as a function of pressure (in-die
measurements). Tablet porosity was calculated and used in the Heckel
equation (Heckel, 1961a,b). The reciprocal of the slope of the linear part of
the in-die Heckel plot was used to calculate the apparent yield pressure
(Duberg and Nyström, 1986). In paper V, out-of-die measurements were
also made, i.e. the materials were compressed at different maximum
compaction pressures and the porosity was calculated from the tablet
dimensions after compaction. An out-of-die yield pressure was calculated
from the reciprocal of the slope of the linear part of the corresponding
Heckel plot (Paronen, 1986). The elastic recovery of the tablets was
calculated as the relative difference between minimum (during compaction)
and maximum (after 48 hours of storage) tablet heights (Armstrong and
Haines-Nutt, 1972).

-Fragmentation properties
In order to estimate the fragmentation propensity of the materials, tablets
were compacted at different compaction pressures in a specially
constructed die using an instrumented single punch press (Korsch EK0,
Germany) (papers II and V). The specific surface area of the tablets was
determined using Blaine permeametry. The degree of particle
fragmentation during compaction was evaluated by plotting the tablet
specific surface area as a function of compaction pressure. The slope was
then used as a measure of the degree of fragmentation (Alderborn et al.,
1985b).
6
COMPRESSION FORCES :

Compression forces are applied during the compression of powders/

granules to get the final product. Pressure in the range of 300 to
3000kg/cm2 is usual for tablet presses. However, the upper limit may be
higher for mechanical or hydraulic ram presses. Tablet parameters can be
varied for different types of tablet presses as they maintain various
compression forces. The force exerted on the powder/ granule in the dies
is, therefore, should very carefully be controlled to ensure that each tablet
is perfectly formed within the specification.It is fairly common for a tablet
press to exert as little as 3,000 and as much as 40,000 lb of force in
production of tablets.
In general, the greater the pressure applied, the harder the tablets,
although the characteristics of the granulation also have a bearing on
hardness. Some tablets, which are intended to dissolve slowly, are
intentionally made hard by using high compression forces. Other tablets,
such as those for immediate drug release, are made soft by using low
compression forces. The porosity of the tablet can be decreased as the
compression force is increased which is attributed to fragmentation of
particles/ granules during the initial stages of compression followed by
bonding of the freshly formed surfaces at higher pressure.
7
BONDING TO TABLETS :

The mechanical strength of a tablet depends on the dominating bonding

mechanism between the particles and the surface area over which these
bonds act. When the surfaces of two particles approach each other closely
enough, their surface energies result in a strong attractive force, a process
called cold welding. This hypothesis is favoured as a major reason for the
increasing mechanical strength of a powder bed when subjected to
compression force. Most particles have an irregular shape, so that there
are many points of contact in the bed of powder. As the force is applied to
the powder bed, this transmission may result in generation of considerable
frictional heat. If this heat is not lost, the local rise in temperature could be
sufficient to cause melting of contact area of the particles, which would
relieve the stress in that particular region. In that case, the melt solidifies
giving rise to fusion bonding.

TYPES OF BONDING IN TABLETS :

The nature of these bonds is traditionally subdivided

into five types, known as the Rumpf classification :
1. Solid bridges
2. Bonding by liquids (capillary and surface tensionPforces)

3. Binder bridges (viscous binders and adsorptionlayers)

8
4. Intermolecular and electrostatic forces

5. Mechanical interlocking

In the case of compaction of dry powders, two of the suggested types of

bond are often considered to dominate the process of interparticulate bond
formation, i.e. bonding due to intermolecular forces and bonding due to the
formation of solid bridges.
Mechanical interlocking between particles is also considered as a possible
but less significant bondtype in tablets.Bonding by intermolecular forces is
sometimes also known as adsorption bonding, i.e. the bonds are formed
when two solid substaces are brought into intimate contact and
subsequently adsorb to each other. Among the intermolecular forces,
dispersion forces are considered to represent the most important bonding
mechanism. This force operates in a vacuum and in a gaseous or liquid
environment up to a separation distance between the surfaces of
approximately 10-100 nm.

The formation of solid bridges, also referred to as the diffusion theory of

bonding, occurs when two solids are mixed at their interface and
accordingly
form a continuous solid phase. Such a mixing process requires that
molecules in the solid state are movable at least temporarily during
compression. An increased molecular mobility can occur due to melting or
as a result of a glass-rubber transition of an amorphous solid phase.
Mechanical interlocking is the term used to describe a situation where
strength is provided by interparticulate hooking. This phenomenon usually

9
requires that the particles have an atypical shape, such as needle-shaped,
or highly irregular and roughparticles.For tablets of a porosity in the range
5-30%, it is normally assumed that bonding by adsorption is the dominant
bond type between particles.

In tablets which are formed from amorphous substances or from

substances with low melting points, it is possible that solid bridges can be
formed across the particle interface. lt is also reasonable that if tablets of a
very low porosity, i.e. close to zero, are formed particles can fuse together
to a significant degree .Often granules, i.e. secondary particles formed by
the agglomeration of primary particles, are handled in a tableting operation.
When granules are
compacted, bonds will be formed between adjacent granule surfaces. For
granules that do not include a binder, the fusion of adjacent surfaces during
compaction is probably not a significant bonding mechanism.
Thus, intermolecular bonding forces acting between intergranular surfaces
in intimate contact will probably be the dominant bond type in such tablets.
Granules often include a binder. When such binder-substrate granules are
compacted it is reasonable to assume that the binder also plays an
important role in the formation of intergranular bonds. The binder may fuse
together locally and form binder bridges between granule surfaces which
cohere the granules to each other. Such bridges may be the result of a
softening or melting of binder layers during the compression phase.

However, different types of adsorption bonds may be active between

granule surfaces. These may be subdivided into three types: binder-binder,
binder-substrate and substrate-substrate bonds.For adsorption bonds
10
between granules in a tablet, the location of the failure during fracturing of
the tablet can vary. Fractures occurring predominantly through binder
bridges between substrateparticles, as well as predominantly at the
intertace between the binder and the substrate particle, may occur. The
location of the failure has been attributed to the relative strength of the
cohesive (binder bridge) and adhesive (binder-substrate interface) forces
acting within the granules.

PROPERTIES OF TABLET :

Such properties of tablet are :

I) Hardness
II) Friability
III) Release rate
IV) Release kinetic
V) Mechanical strength
VI) Pore structure
VII) Tablet dimension

THE EFFECT OF COMPRESSIONAL FORCE ON TABLET

PROPERTIES:

I) Effect of compressional force on hardness :

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Hardness is a measure of tablet strength. Its gives insight into the force
required to break a tablet. It assesses how strong a tablet is to withstand
breakage, crumbling or chipping under the conditions of storage,
transportation and handling. Generally, hardness is dependent on type and
concentration of binder, tablet height to diameter ratio and compression
force. This study has been able to established that keeping all other
manufacturing processes constant and having compression pressure as
the
only variable, there was a great influence on the hardness of the tablet for
the three formulations. Anova analysis reveals a significant difference in
tablet hardness with increase in compression pressure (P<0.001). This is in
agreement with the study carried out by [8,10]. This could be due to gas
displacement from the powder bed in the die as compression pressure
increases bringing particles in close contact. This therefore causes
increase in the number of particle – particle contact within the material
thereby increasing particle - particle interaction leading to formation of a
strong bond which increases the mechanical strength of the tablet at high
compression pressure.

II) Effect of compressional force on friability :

The friability test for tablets is used to assess the ability of the tablets to
withstand shock and abrasion which will be encountered during packaging,
transportation and handling. The friability values were observed to
decrease as pressure increases in all the formulations. This decrease could
have been due to the formation of more solid bonds which led to the
12
formation of tablets with increasing hardness and more resistance to
fracture and abrasion. The friability values were below 1% in formulations
containing Xanthan gum but above 1% in formulations containing SCMC.
According to Odeku and Itiola, convectional tablets which loose less than
1% of their weight during the friability test are generally considered
acceptable.

III) Effect of compressional force on release rate :

Mean dissolution time (MDT), t25, t50, and t75 were obtained from the
dissolution profile and were used to characterize the drug release rate.
Some published articles have shown that compression does not have any
effect on release properties of drugs while some shows that it does. In this
study, it was observed that, the MDT, t25, t50, and t75 increased with
increase in compression pressure for both formulations. However, One way
Anova statistical analysis shows that there was no significant difference in
the release rate of the matrix tablets with changes in compression pressure
(p>0.05). Drug release from matrix tablets takes place as a result of
hydration when the matrix comes in contact with dissolution medium. The
hydrated portion leads to the formation of gel in which the drug diffuses out.
The viscosity of the gel and diffusional path length of the gel layer
determines the release rate rather than the compression pressure or tablet
hardness. It is the rate determining step in matrix tablet dissolution. While
disintegration is not desirable in a matrix tablet, dissolution will occur in the
system no matter how hard. The design of such delivery system is for the
tablet to remain intact and gradually erodes to release its content, if that
structure or
13
design is lost, drug release is not longer controlled, and all will be release
at once which can cause drug dumping. This is one of the problems of
sustained release delivery. Hardness will be of importance when the tablet
crumbles, from the friability, one would know that. And also since the
polymers are soft, at little pressure they form solid compact because they
easily undergo plastic deformation. Several authors have stated that
compression pressure is a statistically significant factor regarding tablet
hardness, but its effect on drug release was found to be minimal.

IV) Effect of compressional force on release kinetics :

To study the effect of compression pressure on drug release, data were

fitted to zero-order, first order, Higuchi and Korsmeyer-Peppas equations.
In this study, the drug release from the two formulations could be best
expressed by Korsmeyer-Peppas equation as the plots showed high
linearity (r2) of 0.998 and 0.988 for formulation containing Xanthan gum
and Sodium Carboxymethylcellulose, respectively. The dissolution data
were also fitted to Korsmeyer- Peppas equation in order to describe the
drug release mechanism from the matrix system. The slope n, diffusion
exponential which indicates the mechanism of drug release was observed
to be between 0.411 and 0.586 and 0.277 and 0.345 for formulation
containing Xanthan gum and Sodium Carboxymethylcellulose respectively.
For cylindrical matrix tablets, an n value ≤ 0.45 indicates a release
mechanism governed by diffusion and 0.45 < n < 0.89 indicates a release
mechanism governed by combination of diffusion and macromolecular
chain relaxation. The n results clearly indicated that drug release is
generally controlled by a combination of diffusion and chain relaxation in
14
formulations containing Xanthan gum while in formulations containing
Sodium Carboxymethylcellulose, drug release is controlled mainly by
diffusion. Therefore, it can be concluded that compression pressure does
not have a significant effect on release rate and mechanisms but rather
polymer type.

V) Effect of compressional force on mechanical strength :

The compaction pressure and speed, and the tablet dimensions, can affect
the mechanical strength of the resulting tablet (Davies and Newton, 1996).
A material which undergoes time-dependent plastic or elastic deformation
is referred to as a viscous or viscoelastic material. For such a material, a
change in the compression speed significantly affects the deformation of
the material (e.g. Roberts and Rowe, 1985; Armstrong and Palfrey, 1989).
The effect of compression speed has been evaluated by calculating the
strain rate sensitivity, which is the relative difference between yield
pressure values at a high and low compression speed (Roberts and Rowe,
1985). For a material known to deform by plastic flow, the volume reduction
generally decreases as the compression speed increases, thus allowing a
shorter time for plastic deformation and a subsequent decrease in
mechanical strength of tablets (David and Augsburger, 1977; Armstrong
and Palfrey, 1989; Cook and Summers, 1990). A fragmenting material, on
the other hand, has been shown to be less affected by variations in
compression speed (Roberts and Rowe, 1985; Armstrong and Palfrey,
1989; Cook and Summers, 1990). The relative humidity and temperature
can affect the compaction process as well as the mechanical strength. The
mechanical strength of a tablet can also be influenced by the time that
15
elapses between compaction and strength characterisation. For example,
in a study of the postcompressional changes of fine particulate sodium
chloride tablets, it was suggested that moisture facilitated the bond
formation process (Eriksson and Alderborn, 1994).

VI) Effect of compressional force on pore structure of tablets :

The pore structure of a tablet can be expressed in terms of porosity and

pore size distribution and is influenced by the mode of volume reduction
during compaction and the compaction pressure applied. Increasing the
compaction pressure brings the particles closer to each other, resulting in a
reduction in tablet porosity. Tablet properties such as mechanical strength
and disintegration are in turn affected by the pore structure. However, the
relationship between mechanical strength and pore structure appears to be
ambiguous. For example, a linear relationship between porosity and the
logarithm of the strength of tablets has been reported (Ryshkewitch, 1953).
This suggests that tablets of low porosity will have high mechanical
strength. Further, the total pore surface area has been suggested to be
directly proportional to the breaking force of lactose tablets, i.e. an increase
in the total pore surface area resulted in an increase in tablet strength
(Vromans et al., 1985; de Boer et al., 1986). However, in another study this
relationship could not be established for lactose or for other materials
(Juppo, 1996). An increase in tablet strength was instead proposed to be
related to a decrease in the volume of large pores and to a shift in the pore
size distribution towards smaller pore diameter (Juppo, 1996). Although it is
reasonable to assume that a low porosity is beneficial to a high tablet
strength, linear relationships are seldom obtained, probably partly because
16
of the influence of the whole pore size distribution. The porosity of tablets
made of plastically deforming materials has been shown to increase with
increased compression speed (Armstrong and Palfrey, 1989; Cook and
Summers, 1990). This is consistent with a decrease in the time available
for plastic deformation as the compression speed increases. Also, a
decrease in particle size of the powdered material has been shown to
increase tablet porosity (McKenna and McCafferty, 1982; de Boer et al.,
1986).
The pore size distribution of a tablet may be assessed by methods such as
gas adsorption (e.g. Stanley-Wood and Johansson, 1980; Westermarck et
al., 1998) or mercury porosimetry (e.g. Stanley-Wood and Johansson,
1980; Juppo, 1996; Westermarck et al., 1998). These techniques are
complementary, in that mercury porosimetry can be used to measure larger
pores (the lower size limit is about 0.003 μm in diameter) while gas
adsorption allows measurement of smaller pores.

VII) Effect of compression pressure on tablet dimensions :

Tablet thickness reduces as compression pressureincreases. This is

expected as increase compression pressure tends to displace gas from a
powder bed due to particle rearrangement which leads to reduction in the
height of the powder bed in the die, thereby leading to volume reduction.
As pressure increases, further rearrangement is prevented, at this stage;
volume reduction is accompanied by deformation. However, statistically,
17
Anova analysis shows that compression pressure had no significant effect
on tablet thickness.

CONCLUSION :

Compaction and compression are an integral processes for the

manufacture of tablets, and it is pertinent to understand the underlying
physics of compaction. Complete understanding of compaction physics still
eludes us, many variables such as inherent deformation behaviour of
drugs/excipients, solid- state properties, and process parameters are
known to affect the final attributes of tablets. A due consideration to the
variables of compaction process, can aid a pharmaceutical scientist to
design optimum formulation devoid of problems such as capping,
lamination, picking, and sticking. Various granulating steps, surface area,
particle size & shape, strength & friability, density and flow properties can
help in deciphering the dynamics of the process. Optimization of excipient,
granulation and compaction forces & equations can help in achieving
satisfactory tensile strength and desired biopharmaceutical properties in
tablet drug products. Using two novel indicators, the initial dissolution rate
(DRi) and extent of dissolution (AUC). The linear relationship between the
DRi and AUC confirmed that the extent of dissolution was almost entirely
dependent on the initial dissolution rate of the drug. Although an increase in
compression force increased the disintegration times of tablets. proved to
be an efficient disintegrant at relatively low concentrations of 2.5-10 %
because it has the ability to rapidly release hydrophobic drug particles from
tablets. However, tablets containing high concentrations of this disintegrant
18
must be protected from atmospheric moisture because storage at high
relative humidities lead to the softening of tablets. This effect must be taken
into account by formulators in countries where tablets will be exposed to
high relative humidities, climatic zones II and IV. Tablets manufactured and
distributed in these regions must be adequately protected against moisture.

REFERENCES :

[1] Sumedha,P. (2015). Evaluation of Compression Force on the

Dissolution
Profile of Paracetamol Tablets.Middle-East Journal of Scientific
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[2] Sofia, M. (2000). Pharmaceutical Binders and Their Function in Directly
Compressed Tablets(kindle version). Retrieved from
https://www.researchgate.net

[3] Olutayo,A. (2015). Effect of compression pressure on mechanical and

release properties of tramadol matrix tablets. Current Issues in Pharmacy
and Medical Sciences, 28(2),120-125. doi: 10.1515

[4] Andries,M. (2003). Effect of compression force, humidity and

disintegrant concentration on the disintegration and dissolution of directly
compressed furosemide tablet.Tropical Journal of Pharmaceutical
Research, 2(1), 125 135. doi: 10.4314

[5] Aulton, E. (2014). Aulton's Pharmaceutics. New York, NY: Elsevier

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