Tablets

Wetting, drying and granulating mechanisms,

classification, formulation, quality control and
elaboration.
Tablet
• They are solid pharmaceutical forms of unit dosage obtained by
mechanical compression of granules or powdery mixtures of one or
several active ingredients with the addition, in most cases, of various
excipients.
The size usually ranges between .5 and 17 mm and the weight between 0.1 and 1.0 g, depending on the dose
of active ingredient, its characteristics and the use for which the tablet is intended.
 Dust
• The FEUM defines powders as solid pharmaceutical forms that
contain the active ingredient(s) and additives finely ground and
mixed to guarantee their homogeneity.

simplest pharmaceutical ma and it is, tablets, capsules, suspensions

 Rheology of solids (powders)

Apparent Flow capacity

volume

Study the Factors that determine the flow properties of solids. Methods for
evaluating flow properties: angular methods, flow through orifices,
compaction, etc.

Apparent and Relative Density Analysis

Granulometric
 GRANULATION METHODS
• Granulation is the process by which primary dust particles are
prepared to adhere and form larger multi-particle structures, known
as granules. 0

• Pharmaceutical granules typically have a size range between 0.2

and 4 mm, depending on their future use.
 The reasons why granulation is often necessary are: o

□ Prevent segregation of powder

mixture components

Polydisperse powder Segregated powder

>e sieve to homogenize the size:

Adantarn da IEDN R4917A7OR_C

The smaller particles are granulated again and

the larger ones are divided by grinding.
 Tablet manufacturing
Binder Liquids
Spraying Granulation
n Accumulation
Mixed
drug excipient Knead or
U
or

Reduction
of size
Screening

Tablet Lubrication
n * Granulation
Formulation
The active ingredients the essential components

Excipients are inert materials that provide characteristics for

satisfactory handling and compression as well as
confer physical, chemical and physicochemical properties.
1 .- Diluents. Chemically and physiologically inert, good compressibility, easily
digestible, cheap and with a tolerable flavor. To adjust weight and obtain a
suitable mass for compressing. Examples are lactose, starch, microcrystalline
cellulose.

2 .-Adsorbents. Substances capable of incorporating fluids while maintaining

an apparently dry state. The most used are starch, lactose, microcrystalline
cellulose, bentonite,
kaolin, magnesium carbonate.

3 .- Binders. Solid substances that act as

cohesive adhesives between particles of powdery materials, subjected to
pressure to form granules. The most used are acacia gum, tragacanth gum,
gelatin, starch mucilage, methylcellulose.

4.- Disintegrants. They promote and accelerate the disintegration of the tablet
when it comes into contact with media of aqueous nature or digestive juices.
Examples are starch, microcrystalline cellulose, sodium carboxymethylcellulose.
5 .- Antifriction agents. They reduce the friction between granules (sliding),
prevent adhesion of the granules with the punches and the matrix (non-stick)
and reduce the friction between particles in compression (lubricants). Talc, corn
starch, magnesium stearate.

6 .- Wetting solvents. To carry out wet granulation, water is used; if water

causes hydrolysis problems, it is replaced with ethyl alcohol or isopropyl alcohol.
7 .- Colorants. They improve the appearance of the tablet, aesthetically, and
serve for product identification. They are incorporated in solution with the
granulating liquid or dry powder in the final mixing stage. It is used at a level of
approximately 0.05%

8 .- Flavorings. They mask the taste of the formulation especially in chewable

tablets. Flavorings used are phenols (menthol, thymol), fruit essences and
chocolate. Also saccharin and aspartame, in some cases sucrose

MIXED
Three essential mixing mechanisms are known: a) by convection, in which a group of
particles of one component moves en bloc to regions occupied by another; b) by
diffusion, when the transfer of isolated particles of one component to regions occupied by
another occurs, and c) by shear, a category that is still a variant of convective.
 DRYING
Operation by which water and other solvents or volatile substances are removed
from a solid body, through heat and mass transfer.

Stove
Perforated or non-perforated trays
 WET GRANULATION

This is the most used method in the pharmaceutical industry as a prior stage in the
manufacture of tablets. It is based on the addition of a binder dispersed in a liquid to
form a solution or suspension. Water is almost always used; sometimes alcohol or
other organic solvent.
DRY GRANULATION

□ In dry granulation methods, particle adhesion takes place due to the

applied pressure.
□ A compact or rolled product is generated which is larger in size than the
required granule size and therefore the required size can be achieved by
crushing and sieving.
Granulation Advantages Disadvantages
Sifting
V Fewer stages □ Special
that equipment
moist. required.
V Densifies the □ It does not
material. improve the
dry Process that has
V Improves compactness of
different separate the
component
object fractionsflow. of components.
a mix □ Problem with
powdery adhesive
granulated depending on
Sieve classification
u 1- ' Improvement
assets.
8N
EITHER
either. Sieve Sieve light (mm)
8 compactness
2.38
□ Problems with
hydrolyzable
EITHER
• 10 2,00 Classification of Powders according to
g

co
14
16
1,40
1,18
d. USP
No. Sieve

O
o
co
EITHER -
in O
Or 1
20
25 8 V Improves flow.
0,850
0,710
drugs (high
Classification
of the Dust
Origin drugs
vegetable
Substance
chemistry

energy
C
U 30 Yo 0,600
V
5 very thick 8 -
C (u
—40 8
Densifies
0,425
the Thick
Moderately thick
20
40
20
40
EITHER 60
80
100
g
YO
ugh
0.250
0,180
material.
0,150
operations).
Fine
Very delicate
60
80
80
120

Wet
a or -
cu C.U.
c
either
200
325
0,075
0,045
□ Many
EI
U nj
400 0,038
T
H r CC
E
R ASTM: American Society for testing and materials
Compression
The term compression is considered as an
increase in the density of the powder as a
result of the displacement of air from the
solid phase.

Compression occurs due to the deformation

of the particles, that is, the change in their
shape and volume when they are subject to
a mechanical force; and this will depend on
the characteristics of the material.
TABLET MACHINE
 Aspect
Characters Color, Flavor
organoleptic Texture

ace Shape and markings

Dimensions
(diameter,
Characters crown, border)
Resistance to
geometric fracture
(Hardness)
Endurance
Characters mechanics
I ( d F e ri n a t b id il a id

CONTROL OF mechanical d a de ) l

active principle
QUALITY Essay of
active principle
(Assessment)
Composed of
degradation
Contained in
water
Characters (Humidity)
Uniformity of
posological weight
Uniformity of
content

Bioavailability Time of
disintegration
characteristics Dissolution
 Component mg/Tablet
Active ingredient 150
Microcrystalline cellulose 100
Starch 100
croscarmellose sodium 75
Magnesium stearate 75
Tablet Weight 500
COMPONENTS PERCENTAGE BY Content in
WEIGHT/UNIT milligrams/dose unit
DOSE

Tinidazole 50 500mg
Fluconazole 3.7 37.5mg
Clindamycin (As clindamycin hydrochloride 32.5 312.5mg
Clindamycin) 1

Microcrystalline cellulose PH 102 7.5 85mg

Sodium starch glycolate 0.6 6.5mg
Crospovidone 1.6 17mg
sodium lauryl sulfate 0.6 7mg
Polyvinyl pyrrolidone 1.9 20mg
Magnesium stearate 0.3 3.2mg
Methacrylate derivatives (white Opadry) 1 10.5mg

Isopropyl alcohol — —

Purified water cbp cbp