3. Introduction
1843 a patent was granted to Thomas
Brockedon (Englishman) for manufacturing
pills and lozenges
1874 both rotary and eccentric presses
1885 glyceryl trinitrate tablets was in the
BP
No other tablet monograph appeared until
1945
1980 nearly 300 monographs for tablets
4. Advantages
Production aspect
– Large scale production at lowest cost
– Easiest and cheapest to package and ship
– High stability
User aspect (doctor, pharmacist, patient)
– Easy to handling
– Lightest and most compact
– Greatest dose precision & least content variability
– Coating can mark unpleasant tastes & improve pt.
acceptability
5. Disadvantages
Some drugs resist compression into dense
compacts
Drugs with poor wetting, slow dissolution,
intermediate to large dosages may be
difficult or impossible to formulate and
manufacture as a tablet that provide
adequate or full drug bioavailability
Bitter taste drugs, drugs with an
objectionable odor, or sensitive to oxygen or
moisture may require encapsulation or
entrapment prior to compression or the
tablets may require coating
7. Ingredients used in tablet
formulations
Drugs
Fillers, diluent, bulking agent
– To make a reasonably sized tablet
Binders
– To bind powders together in the wet
granulation process
– To bind granule together during compression
Disintegrants
– To promote breakup of the tablets
– To promote rapid release of the drug
8. Lubricants
– To reduce the friction during tablet ejection
between the walls of the tablet and the walls of
the die cavity
Glidants
– Reducing friction between the particles
– To improve the flow properties of the granulations
Antiadherants
– To prevent adherence of the granules to the
punch faces and dies
10. Essential properties of tablets
Accurate dosage of medicament, uniform in
weight, appearance and diameter
Have the strength to withstand the rigors of
mechanical shocks encountered in its
production, packaging, shipping and
dispensing
Release the medicinal agents in the body in a
predictable and reproducible manner
Elegant product, acceptable size and shape
Chemical and physical stabilities
11. Types of tablets
Route of administration
– Oral tablets
– Sublingual or buccal tablets
– Vaginal tablets
Production process
– Compressed tablets
– Multiple compressed tablets
Tablet within a tablets: core and shell
Multilayer tablet
12. –Sugar coated tablets
Protect tablets from moisture
Mask odor and flavor
Elegance
–Film coated tablets
Thin film coat
Soluble or insoluble polymer film
14. Tablet production
Powders intended for compression into tablets must
possess two essential properties
– Powder fluidity
The material can be transported through the
hopper into the die
To produce tablets of a consistent weight
Powder flow can be improved mechanically by
the use of vibrators, incorporate the glidant
17. Tablet compression machines
Hopper for holding and feeding granulation to be
compressed
Dies that define the size and shape of the tablet
Punches for compressing the granulation within
the dies
Cam tracks for guiding the movement of the
punches
Feeding mechanisms for moving granulation
from the hopper into the dies
22. Multi-station rotary presses
The head of the tablet machine that
holds the upper punches, dies and
lower punches in place rotates
As the head rotates, the punches are
guided up and down by fixed cam
tracks, which control the sequence of
filling, compression and ejection.
The portions of the head that hold the
upper and lower punches are called the
upper an lower turrets
23. The portion holding the dies is
called the die table
The pull down cam (C) guides
the lower punches to the
bottom, allowing the dies to
overfill
The punches then pass over a
weight-control cam (E), which
reduces the fill in the dies to
24. A swipe off blade (D) at the end
of the feed frame removes the
excess granulation and directs
it around the turret and back
into the front of the feed frame
The lower punches travel over
the lower compression roll (F)
while simultaneously the upper
25. The upper punches enter a
fixed distance into the dies,
while the lower punches are
raised to squeeze and compact
the granulation within the dies
After the moment of
compression, the upper
punches are withdrawn as they
26. The tablets strike a sweep off
blade affixed to the front of the
feed frame (A) and slide down a
chute into a receptacle
At the same time, the lower
punches re-enter the pull down
cam (C) and the cycle is
repeated
27.
28.
29. Although tablet compressing
machinery has undergone
numerous mechanical
modifications over the years,
the compaction of materials
between a pair of moving
punches within a stationary die
has remained unchanged
The principle modification from
earlier equipment has been an
increase in production rate
30. Special adaptations of tablet
machines allow for the
compression of layered tablets
and coated tablets
A device that chills the
compression components to
allow for the compression of
low-melting point substances
32. Direct compression
Tablets are compressed directly from
powder blends of the active ingredient
and suitable excipients
No pretreatment of the powder blends
by wet or dry granulation procedures is
necessary
34. – Elimination of granulation process
Heat (wet granulation)
Moisture (wet granulation)
High pressure (dry granulation)
Processing without the need for moisture
and heat which is inherent in most wet
granulation procedures
35. Avoidance of high compaction pressures
involves in producing tablets by
slugging or roll compaction
– Elimination of variabilities in wet
granulation processing
Binders (temp, viscous, age)
Viscosity of the granulating solution
(depend on its temp),
How long it has been prepared,
36. Rate of binder addition and kneading
can affect the properties of the
granules formed
The granulating solution, the type
and length of mixing and the method
and rate of wet and dry screening can
change the density and particle size
of the granules, which can have a
major effect on fill weight and
compaction qualities
37. Type and rate of drying
can lead not only to critical changes in
equilibrium MC but also to unblending
as soluble active ingredients migrate to
the surfaces of the drying granules
More unit processes are incorporated in
production, the chances of batch-to-batch
variation are compounded
38. – Prime particle dissociation
Each primary drug particle is liberated
from the tablet mass and is available for
dissolution
Disintegrate rapidly to the primary
particle state
39. – Uniformity of particle size
– Greater stability of tablet on aging
Color
Dissolution rate
Fewer chemical stability problems would
be encountered as compared to those
made by the wet granulation process
40. Concerns
– Excipient available from only one
supplier and often cost more than filler
used in granulation
– Procedure conservation
– Machine investments
– Lack of material knowledge
41. –Physical limitation of drug
No compressibility
No flowability
–Physical characteristics of
materials (both drug and
excipient)
Size and size distribution
Moisture
Shape and surface
43. Direct compression fillers
Common materials that have
been modified in the chemical
manufacturing process to
improve fluidity and
compressibility
44. Soluble fillers
Lactose
– Spray dried lactose
Lactose is placed in aqueous solution,
removed impurities and spray dried
Mixture of large alpha monohydrate
crystals and spherical aggregates of
smaller crystals
Good flowability but less
compressibility
Poor dilution potential
45. Loss compressibility upon initial
compaction
Problem of browning due to
contamination of 5-hydroxyfurfural
which was accelerated in the presence
of basic amine drugs and catalyzed by
tartrate, citrate and acetate ions
46. – Fast-Flo lactose (early 1970s)
Spherical aggregates of microcrystals
lactose monohydrate
Held together by a higher concentration
of glass (amorphous lactose)
Much more compressible
Highly fluid
Non hygroscopic
47. Tablets are three to four times harder than
regular spray dried
– Tabletose: aggromerate form of lactose
More compressible than spray dried but less
compressible than Fast Flo lactose
48. – Anhydrous lactose: free flowing crystalline
lactose
Produced by crystallization above 93C
which produces the beta form
Pass through steam heated rollers
Good flow property, contained high
amount of fines, its fluidity is less than
optimal
Can be reworked
49. At high RH anhydrous lactose will pick
up moisture forming the hydrated
compound increase in the size of
tablets if the excipient makes up a large
portion of the total tablet weight
Excellent dissolution property
50. Sucrose
–Di-Pac: cocrystallization of
97% sucrose and 3% modified
dextrin
Small sucrose crystals
glued together by dextrin
Good flow properties and
needs a glidant only when
atmospheric moisture levels
51. Concentration of moisture
is extremely critical in
terms of product
compressibility
compressibility increases
rapidly in a moisture range
of 0.3-0.4%, plateaus at a
level of 0.4-0.5% and rises
again rapidly up to 0.8%
52. Dilution potential 20-35%
Tablets tend to harden
slightly during the first
hours after compression or
when aged at high
humidities and then dried
(this is typical of most direct
compression sucroses or
dextroses)
53. –Nutab: 95.8% sucrose, 4%
convert sugar (equimolecular
mixture of levulose and
dextrose) and 0.1 to 0.2%
each of cornstarch and
magnesium strarate
Large particle size
distribution and good
fluidity
54. Dextrose
–Emdex: spray crystallized
90-92% dextrose, 3-5%
maltose and the remainder
higher glucose
polysaccharides
Available both anhydrous
and a hydrate product
Excellent compressibility
Largest particle size,
55. Sorbitol
–Exists in a number of
polymorphic crystalline forms
and amorphous form
–Widely used in sugar-free
mints and as a vehicle in
chewable tablets
–Cool taste and good mouth
feel
–Forms a hard compact
56. –Hygroscopic and will clump
in the feed frame and stick to
the surfaces of the die table
when tableted at humidities >
50%
–Lubricant requirements
increase when the MC of the
sorbitol drops below 0.5% or
exceeds 2%
57. Mannitol
–Exists in a number of
polymorphic forms
–Not make as hard a tablet as
sorbitol
–Less sensitive to humidity
–Widely used where rapid and
complete solubility is
required
59. Insoluble fillers
Starch
–Starch 1500: intact starch
grains and ruptured starch
grains that have been
partially hydrolyzed and
subsequently aggromerated
Extremely high MC (12-13%)
Does not form hard
compacts
60. Not generally used as filler-
binder but as filler
disintegrant
–Retains the disintegrant
properties of starch without
increasing the fluidity and
compressibility of the total
formulation
–Deforms elastically when a
compression force is applied,
it imparts little strength to
61. –Spray dried starch
Era-Tab: spray-dried rice
starch
Good fluidity
MC 10-13%
Compressibility depend
on moisture
Reworkability
Low bulk density
62. Celulose
–Microcrystalline cellulose
(Avicel)
The most important tablet
excipient developed in
modern times
Derived from a special
grade of purified alpha
wood cellulose by severe
acid hydrolysis to remove
the amorphous cellulose
63. PH101 powder
PH102 more agglomerated,
larger particle size, slightly
better fluidity but not
significant decrease in
compressibility
Most compressible
Highest dilution potential
64. A strong compact is formed
due to the extremely large
number of clean surfaces
brought in contact during
the plastic deformation and
the strength of the
hydrogen bonds formed
Extremely low coefficient of
friction, no lubricant
requirement
When >20% of drugs or
65. Not used as the only filler
because of its cost and
density
Usually used in the conc of
10-25% as a filler-binder-
disintegrant, rapid passage
of water into the compact
and the instantaneous
rupture of hydrogen bonds
66. Fluidity is poor because of
its relatively small particle
size, small amount of
glidant are recommended in
the formulations containing
high conc of MCC
Tablets are soften on
exposure to high humidities
This softening is reversible
when tablets are removed
from the humid environment
>80% MCC may slow the
67. Small particles get
physically trapped between
the deformed MCC particles,
which delays wetting and
dissolution
This phenomenon can be
overcome by adding
portions of water soluble
68. Inorganic calcium salts
–Dicalcium phosphate
(Emcompress or DiTab)
Free flowing aggregates of
small microcrystals that
shatter upon compaction
Inexpensive and possesses
a high degree of physical
and chemical stability
69. Slightly alkaline with a pH of
7.0 to 7.3
Precludes its use with AI
that are sensitive to even
minimal amounts of
alkalinity
–Tricalcium phosphate (TriTab)
is less compressible and less
70. References
ยาเม็ด (ม.มหิดล)
Pharmaceutics. The science of
dosage forms design. (M.E.
Aulton)
The theory and practice of
industrial pharmacy.
Pharmaceutical dosage forms
: Tablets. Volume 2.
