TABLET dosage Form.pdf

Method types of tablet coating .
Coating equipment

1. Solid Oral Dosage Forms

PRASHANT PANDEY
M.Pharm (Pharmaceutics)
C.S.J.M University, Kanpur

[email protected]

2. FORMS

« Powders
« Pills

+ Troche

» Capsules
+ Tablets

3. Most Common Dosage Forms

° Convenient

* Relatively Stable

+ Easily Administered
« Palatable

» Flexible

4. «ablets & Compactio,,

5. Introduction

+ Tablets: Solid preparations each containing
a single dose of one or more active
ingredients and obtained by compressing
uniform volumes of particles.

« They are used for local 8.
systemic effect.

« Usually used for oral administration.

6. Tablets are popular due to:
. A convenient and safe way of drug

administration.

. Compared to liquid dosage form th
more physically & chemically stable

. Enables more accurate dosing. —_—>
==

——.

7. 4,

Convenient to handle and can be
prepared in different ways according to
their use.

They can be mass produced ,
with quality-controlled productio
procedures giving an elegant
preparation of consistent quality
and low price.

—

=>

——.

8. Disadvantages of tablet:
. It's not suitable for poorly water-soluble
or poorly absorbable drugs ===} less
bioavailability.

. Enhances local irritant effect of some
drugs or cause harm to the
gastrointestinal mucosa.

. Some drugs resist compression =
into dense compacts. ar

AAA

9. 1.

|2.

aualit tiribut fablets:
The tablet should include the correct dose
of the drug.

The appearance of the tablet should be
elegant and its weight, size
and appearance should be

consistent.

. The drug should be released a 3

from the tablet in a controlled —
and reproducible way. — |

10. 4. The tablet should be biocompatible .

5. The tablet should be of sufficient
mechanical strength to withstand
fracture and erosion during handling.

6. The tablet should be = =
chemically, physicallyand |
microbiologically stable =

——.

12. Compressed Tablet

+ Un-coated

+ Inunediate Release

13. . Cam tracks for guiding the

Tablet Compression Machine

Hopper for holding and feeding granules or
powder to be compressed.

Dies that define the size and shape of the
tablet.

Punches for compressing the

granules within the dies. ==

movement of the punches.
. Afeeding mechanism for
moving granules from the
hopper into the dies.

14. Tablet tooling; punches and dies

15. Tablet machine or tablet press

16. Stages of Tablet Formation
(Compaction Cycle)
Die fill
Gravitational flow of the powder from
hopper via the die table into the die .
(The die is closed at its lower end by the lower
punch).

The upper punch descenas,

enters the die ,the powder is

compressed until a tablet is formed.

- after maximum applied force is reache:
the upper punch leaves the powder.

17. Tablet ejecti

The lower punch rises until its tip reaches
the level of the top of the die.
The tablet is subsequently removed from

the die and die table by
a pushing device.

18. _ The compression cycle fora single
| punch tablet machine

First stage Second stage Third stage

Hopgser SN
R

Granules Top
punch
holder
Top
punch

Ejected
tablet

Lower punch holder.

|

Collection and filling Compression Ejection

20. Stages of Tablet Formation
(Compaction Cycle)
1. Forcing particles into close proximity to
each other by powder compression.
2. Compression takes place in a die by the

action of two punches (lower & Upper).
Powder compression

The reduction in volume of a powde =
owing to the application of a force. ¡[2
compaction

ee

The formation of a porous specimen
defined geometry by powder compréssion.—

21. Tablet Presses

* Single Punch
+ Rotary Press
* High Speed Rotary Press
¢ Multi-layer Rotary Press

22. ‘Tablet Presses |

bench-top models that make one tablet at
a time (single-station presses)

Disadvantages: Production of
small batches of tablets
(200 tablets per minute).

23. 2. Rotary Press( Multi station Press):
It was developed to increase the output of
tablets (10 000 tablets per minute), used for
Large scale production.

It consists of a number of dies and sets of
punches ( from 3 up to 60).

The dies are mountedin a circle in =
table and both the die table &

the punches rotate together A
during operation of the machine. FT

24. Rotary Press Machine

25. al

Rotary Press Machine

26. The powder is held in a hopper whose lower
opening is located just above the die table.

The powder flows on to the die table & fed into the
die by a feed frame.

During powder compression both
punches operate by vertical
movement.

After tablet ejection, the tablet is
knocked away as the die passes the
feed frame.

28. Tablet Ingredients (excipients)

» Active + Non-Active
- Drug Substance - Diluents

- Binders
- Lubricants
- Disintegrants
- Coloring
- Flavoring
- Antiadherents
- Glidants

29. Tablets Exeipfeni

+ Their role: To ensure that tablets of
specified quality are prepared.

« The common types
of tablet's excipients
are described in the
figure.

DAS

30. | 1. Filler or Diluent

Use: Increase the bulk volume of the
powder and hence the size of the tablet
suitable for handling .

Therefore, is not necessary if the dose of
the drug per tablet is high.

Most common fillers in tablets: me
. Lactose.
. Sugar or sugar alcohol (glucose, J
sucrose, sorbitol and mannitol). a L

. Cellulose and microcrystalline cel
Dicalcium phosphate dihydrate.

31. CO ND — ee

. Good technical properties

. Have an acceptable taste.

1. Filler or Diluent

Requirements for a good filler:

. Chemically inert, biocompatible, cheap.
. Non-hygroscopic.
. Good biopharmaceutical properties.

(water soluble or hydrophilic).

(compactability )

32. 2. Disintegrant

Role: To ensure that the tablet, when in
contact with a liquid, breaks up into
small fragments, which promotes rapid
drug dissolution.

33. 2. Disintegrant
St the disint ti

> First: The liquid wets the solid and

| penetrates the pores of the tablet ==» the
tablet breaks into smaller fragments

(aggregates of primary particles).

+ Second: The aggregates will
deaggregate into their primary

powder particles.

34. 2. Disintegrant

Mode of action:
1. Facilitate water uptake into the pores of tablet,
e.g. surface active agents

2. Facilitate rupture of tablet by swelling during
water sorption,

e.g. starch, modified cellulose
3, Release of gases to disrupt the
tablet structure, normally
carbon dioxide, in contact
with water. e.g. effervescent
tablets.

shape in contact with water.

35. The Method of Disint t Addition:
1. Mixed with other ingredients prior to

granulation & thus incorporated within the
granules (intragranular addition).

| 2. Mixed with the dry granules before the
complete powder mix is compa
(extragranular addition).

3. Incorporated as both an

intragranular and an extragranula——
portion. |

36. | Comme ly U | Disintegrant .

1.Starch.

2. Cellulose (e.g. sodium
carboxymethyl cellulose).

- Typical concentration of 1-5% by

weight -

3. High swelling disintegrants =

(Modified Starch or Modified
cellulose, in concentration of 152%

—

——.

37. Starch

« The typical concentration range of
starch in a tablet formulation is up to
10%.

1. Starch particles swell in contact

with water and this swelling can
subsequently disrupt the tablet.

2. Facilitate disintegration by
particle-particle repulsion.

38. 3. Binder

Role: Ensure that granules and tablets

* Starch Paste
* Glucose

* Acacia
* Sucrose
+ Sodium Alginate

can be formed with the required

mechanical strength ( glue that holds
powders together to form granule:

Gelatin Solution

39. 3. Binder
Incorporation of binder
1. Dry Powder

- As dry powder mixed with other ingredient before wet
granulation
- As a dry powder in dry granulation (roller compaction,
slugging)

2. i inder

As a solution in wet granulation. Binder can be added
either dry with other excipients for granulation or alrea
dissolved in the granulating fluid; water is the most
common granulating fluid, very occasionally in a co-
solvent system with, e.g. ethanol.

40. 3. Binder

* Typical binder concentration is 2 - 10%

by weight

« Binders can be:

— Insoluble in water, e.g. starch
— Soluble in water e.g. HPMC
— Soluble in water and ethanol e.g.

Povidone

41. - Fluid lubrication.

4 Lubricant

Role:
Lubricants prevent adherence of granule/powder

to die wall and to promote smooth ejection from
the die after compaction

Mecheni Action:

Boundary lubrication.

42. + 1 Fluid lubricati
+ A layer of fluid is located between

the

moving surfaces separating them from
each other & thus reduces the friction,

e.g. liquid paraffin.

* The sliding surfaces are separated y=
by only a very thin film of lubricant —=

So, the nature of the solid surfaces
will therefore affect friction.

a

==

——.

43. Disadvantages of lubricants

+» 1. Lubricants tend to be hydrophobic, so their
levels (typically 0.3 - 2%) need to be
optimised:

— Under-lubricated blends tend to flow poorly
and show compression sticking problems
Over-lubricated blends can adversely affe
tablet hardness and dissolution rate, as w
as tablet strength.

— To overcome these problems;
- optimum conc. < 1%
- Addition of SAA

- order of mixing, in the last step =

44. Commonly used Lubricants

« Magnesium Stearate

« Calcium Stearate

+ Talc

« Stearic Acid

« Sodium Lauryl Sulfate, liquid

Paraffin, propylene glycol
(PG)

45. - Talc ( at concentration 1-2 % ).

w Pa
. Colloidal silica ( 0.2% >

5. Glidant (flow aid}

Role: Improve flowability of the powder &
added during direct compaction and to
granulation before tabletting ( they reducing
interparticulate friction).

Common Glidants:

46. 6. Antiadherant

« Role: Reduce adhesion between the
powder and the punch faces &thus
prevent particles sticking to the punches;

due to excess moisture or engraved and/or
embossed punch face.

« Many lubricants, such as
magnesium stearate, have
also antiadherent properties.
Also tale and starch can act
as antiadherents.

47. 7, Sorbent

+ Def.: Are substances that are capable of
sorbing some quantities of fluids in an
apparently dry state.

Thus, oils or oil-drug solutions can be
incorporated into a powder
mixture which is granulated

& compacted into tablets.
e.g. Microcrystalline cellulose
& silica.

48. 8. Flavour

« Give the tablet a more pleasant taste or to
mask an unpleasant one.

« Flavouring agents are often thermolabile
and so cannot be added prior to an_
operation involving heat.

« They are often mixed with the
granules as an alcohol solution.

49. 9. Colourant

|. It is added to tablets to aid identification
and patient compliance.

¡+ It is added during coating.

« It can also be added prior to
compaction. (can be added as an : -
Insoluble powder or dissolved in the L

granulation liquid). A ——

50. 10. Sweetener

« They are used in chewable tablet to exclude or
limit the use of sugar in the tablets.

e.g. Mannitol, 72% as sweet as sucrose.

| Saccharin, 500 times sweeter than
sucrose. Disadv.: has a bitter taste after time |
and carcinogenic. =

Aspartame, Largely replace saccharin.
Disadv.: Lack of stability in the
presence of moisture.

51. tablet Productio,,

52. The Tablet Manufacturing Process

The tablet manufacturing process is the step
by step, individual operations required to
make powders into a tablet.

This is known as individual units of operation;
or commonly referred to as
Unit Operations.

Weighing, Blending and Tableting
are unit operations in the tablet
manufacturing process.

53. The Tablet Manufacturing Process

« Powders must Flow and Compress in order to
make a good tablet.

« We may need to add many unit operations to
make the powders perform.

« Each different formula may have a
different number of unit operations,
which is based completely on the
ability to Flow and Compress and
then eject from the tablet press.

54. Tablet Production

¢ Tablets are prepared either by:
« Pre-granulation.

¢ Direct compression

— Wet granulation
— Dry granulation

55. . Avoid the hazard of generation of

. Increase the bulk density of the powder.
. Improve powder's flowability, i.e. uniform

die feed.

. Reduce segregation .
. Improve powder's compactability

by adding a solution binder.

toxic dust.

. Avoid caking of hygroscopic - a

powder on storage. =

56. Segregation

. Segregation (demixing) is due to:
1. Differences in size.

Differences in density of the components of the mix

N.B.The smaller &/or denser particles at the base of the
container & larger &/or less dense ones above them.

57. * Ideal granulation : each granule will
contain all the constituents of the mix.
in the correct proportion.

¢ [tis important to control particle size
distribution of the granules,
why???

58. Granulation overview
A process of size enlarging a mix of active
ingredient and excipient powder particles into

stable aggregates exhibiting desired
properties of:

Compressibility

Cohesiveness

Flowability

Bulk density

Granules may be a final product

or an intermediate product that
needs further processing

59. Primary powder
particles

adhere

Granules
(larger free flowing multiparticles

+ Granules size 0.2 - 4 mm (depending on the ús

(In tablets & capsules (When used asa Dosage form)
production) typical size =

‚is 0.2-0.5mm.

60. Granulation Steps

- Initial dry mixing of powdered

ingredients (to achieve uniform
| distribution of each ingredient
_ through the mix.).

- Granulation.

- Mixing with other excipients prior te
tablet compaction or capsule fillin

62. WET GRANULATION

« Itinvolves massing of a mix of dry
primary powder particles using a
granulating fluid.

« The fluid contain a solvent that must be
volatile and non-toxic e.g water,
ethanol.

« The granulating solvent may con
binding agent to ensure particle
adhesion after drying.

63. Tablet Production via Wet G lator

Process description:
« Agitation of a powder by convection in the
presence of a liquid.

« It forms the granules by binding the powders
together with an adhesive.

+ Once the granulating liquid has been
added, mixing continues until uniform
dispersion is attained (15 min. to an hour).

64. The mass should merely (just) become
moist rather than wet or pasty (there is a
limit to the amount of solvent that may be
employed).

Overly wet material would block the
screens & prolong the drying
processing.

End point is tested by pressing
a portion of the mass in the
palm, if it crumbles (passed)
under moderate pressure then,
the mixture is ready for wet
screening.

65. The moist mass is broken up into coarse,

granular aggregates (using screens with large
perforations).

The purpose is to increase surface area to
facilitate removal of moisture.

Sreening the dry granules

Mixing with other tablet XIE

(lubricant, glidant, remaining of
disintegrant) and then compacto

——.

66. Mixers and Blender

Planetary Mixer

« Good horizontal mixing
* Cross contamination risk
« Poor vertical mixing

67. WET GRANULATION STEPS

Wet Granulation Manufacturing Steps

E
o

68. Drying process

A process of evaporating the liquid
contained within aggregates

produced by a wet granulation

process to a predetermined moisture
content >
Accomplished via direct (tray dry
or indirect (fluidized bed dryer)
contact of the product with the
heating medium

70. Fluid Bed Dryer

71. Single Step Technology for Wet
Granulation
Single machines utilized for both the
wet granulation and drying process in
one unit operation.
Use Fluid Bed Dryer (FBD)
It is a multiple step process performed
in the same vessel to mix, granulate
and dry the powders.
Combines wetting the powders to
form granules &then, drying them in
the same piece of equipment.

72. Advantages of FBD

+ Reduced product handling
+ Closed process suitable to:
O Potent compounds
Minimizing product/operator
Ü exposure
O Minimizing cross contamination and
product loss
o Reduced cleaning and overall
process time

+ Reduced equipment and floor space
requirements

73. FBD

« Powder bed is fluidized

for dry mixing and is |
wetted with an \ na Joa
agglomeration solution Vo =
introduction as a fine jo J \ note

. \ dejó]
mist. as “a

+ The agglomerated y

material remains = ao
fluidized during hot air N

drying

74. Spray Drying
Best granules, regarding homogeneity,
flowability and compactability.
The tablet components are suspended
/or dissolved in a suitable vehicle
according
to their nature.
The slurry is pumped to an atomizing
wheel which whirls the materialinto a #
stream of hot air Under constant stirring 7
to maintain good distribution.
The heat removes the liquid carrier and
the solids fall to the bottom of the dryer f
as a fine spherical granulate (10 - 250
um).

75. Steps of granule (agglomerate)
formation by FBD

spraying wetting solid fying final granule

¿eye 7)
RER

binder powder liquidbridges — solidbridges — “raspbery"-structure
droplet

77. (1) Avoid exposure of the powder to
moisture and heat.

| (2) Used for powders of very low

| bulk density to T their bulk density,
|

- Tablet disintegration and dissoluti
may be retarded due to doubl —
lubrication and compaction “=~

78. ¢ The blend of finely divided powders is
forced into the dies of a large capacity
tablet press.

« Then, compacted by means of flat faced

| punches (Compacted masses are called slugs

and the process is slugging) Or roll
compactor to produce sticks or
sheets.

e Slugs or sheets are then milled/scréé
to produce granules (flow more than ,
the original powder mixture). a

79. Roller compactor

80. Primary powder particles
aggregated under high
Pressure. Granulating fluid

Mix of dry primary powder particles

Wet mass

Slugging Roller Forced through a

To produce a compaction

large tablet Powder is
(slug) ina squeezed
heavy duty between 2 +

tabletting rollers to
press produce a

sheet of
material

Wet granules

y

Break agglomerate

granules & remove
Intermediate product particles.

81. +Hrtermediateproduct

broken
(suitable
milling
technique)

Granular material
sieved
Separate the

desired size
fraction.

Typi
%

The fluid-contains a solvent,; which
must be:

volatile so that it can be removed

by drying.
be non-toxic.

ical liquids include:
water may adversely affect drug

stability, causing hydrolysis ‚it .
needs a longer drying time. This

increases the length of the

process. The advantage :non-
flammable and

Ethanol, Isoprop)

when rapid dryingtime is
required. u ~

83. Tobe produced by dec! compression

e It involves only two unite operations
powder mixing and tabletting.
+ Advan Direct C tion:
1. Reduced production time &Cost. =
2. Product stability can
be improved.
3. Faster drug dissolution due to fast yl
disintegration into primary parier

84. Large particles must be used > (acceptable
flowability and bulk density)

If the drug powder has low compactabilty, it is
difficult to form into tablets.

Needs directly compressible filler that

is usually expensive, e.g. microcrystalline’
cellulose (Avicel), spray dried lactose.

85. - D Lin Direct C Hom

1. Soluble drugs which can be processed as
coarse particles (to ensure good flowability).

2. Potent drugs which are present in a few

mgs in each tablet (mixed with relati
coarse excipient particles).

86. st Tablet presinchion by Direct

Compaction:
- Drug
- Filler

¢ Dry binder
e Disintegrant
¢ Lubricant

87. NB.

Every granulation should start with
materials that have been ground to the
same approximate particle size, so that
they will blend uniformly in the mixing
step.

88. Technical pı problems during tabletting:

BINDING | Chipping 8:
Cracking |

89. . Binding:

It is the adhesion of the granules to the die wall
and this cause the resistance of the tablet to
eject from the die, it is usually due to insufficient
lubrication, which produce tablets with rough
and vertical score marks on the edges.

Solution:

1. Increasing lubrication.

2. Improve lubricant distribution.

3. Increasing the moisture content
of the granulation.

90. Adhesion of the material to the punch faces.
Sticking : (whole adhesion)

Is usually due to improperly(incorrectly) dried or
lubricated granulation causing the whole tablet
surface to stick to the punch faces — dull,
scratched, or rough tablet faces.
Pickina : (localized adhesion)

Is a form of sticking in which a small
portion of granulation sticks to

the punch face & a portion of the
tablet surface is missed.

91. =

Stickingoccurs when particles
adhere to the punch face

92. Picking

93. Eilming: is a slow form of sticking and is largely
due to excess moisture in the granulation.

94. à Capping & Laminofina:

Capping occurs when the upper
segment of the tablet separates from the

main portion of the tablet & comes off as
a cap.

e It is usually due to air entrapped :
in the granulation which is :
compressed in the die during the
compression & then expands
when the pressure is released.

95. Capping Lamination

96. « Reasons of capping: 1. large amount of fines in
the granulation &/or the lack of sufficient
clearance between the punch and the die wall.

2. In new punches and dies that are tight fitting.

3. Too much or too little lubricant or excessive
moisture.

Lamination is due to the same
causes as capping except that
the tablet splits at the sides into
two or more parts.

If tablets laminate only at certain
stations, the tooling is usually the cause a

97. Solutions! —

. Increasing the binder.
. Adding dry binder such as gum acacia ,
PVP or powdered sugar.
Decreasing the upper punch
diameter.

98. It is an Unequal distribution of color on the surface
of the tablet.

99. + Cause: 1. A drug that differs in color from its
excipients or whose degradation products
are highly colored.

2. Migration of a dye during drying
of a granulation (change the solvent
system, reduce the drying temperature,
or grind to a smaller particle size).

100. Tablets Types

« Tablets can be classified according to
their drug-release characteristics into:

Immediate release |

101. The drug is intended to be released rapidly
after administration, or the tablet is
dissolved and administered as a solution.

This is the most common type of tablet &
includes disintegrating, chewable,

effervescent, sublingual & buccal .
tablets. +

- Should normally be swallowed intact.
- Different excipients than —
immediate release tablets.

102. The drug is released from an extended-release
tablet slowly at a nearly constant rate.

Delayed-release tablets

The drug is liberated from the tablet some time
after administration.

After this period has elapsed, the release is
normally rapid.

e.g. Enteric tablet, for which the drug is =
released in the upper part of

the small intestine after the
preparation has passed the stomach.

103. A delayed-release can also be
combined with a slow drug release, e.g.
for local treatment in the lower part of
the intestine or in the colon.

105. 1. Disintegrating tablets

e Most common type is intended to be
swallowed and release the drug in a relatively
short time after disintegration and dissolution

| thus fast & complete drug release in vivo
(conventional or plain tablets).

« A disintegrating tablets include the following
types of excipients: filler (if the dose of drug is
low), disintegrant, binder, glidant, lubricant
and antiadherent.

Tablet à Drug h \ Drug

_’ disintegration “ “dissolution / 4 absorption 4

Steps of drug release from disintegrating tablets

106. — 2. Chewable tablets
« They are chewed so mechanically disintegrated in the

mouth.
« The drug is not dissolved in the mouth but swallowed
and dissolves in the stomach or intestine.

Lo of chewable tablets:
. Quick and complete disintegration of the tablet - and

tablets.
3. Can be taken when water is not available, { ==

They are similar in composition to conventional tablets
except that a disintegrant is normally not ie ud ed .

107. 3. Effervescent tablets

Effervescent tablets are dropped into a glass of water

before administration, during which carbon dioxide is
liberated.

[ weakacia \ |
a CO, |
NY >

facilitates tablet |
disintegration and drug ~
dissolution; the dissolution
of the tablet should be
complete within a few

108. Uses of effervescent tablets:
1. Rapid drug action, e.g. analgesic drugs .
2. Facilitate the intake of the drug, e.g. vitamins.

temporarily
increases the pH
of the stomach.

Dissolution of buffered water
| tablets > solution —>

rapid emplying
of the stomach
and shortening
the residence
time |

fast drug bioavailability

(As drugs are absorbed
more effectively in the
small intestine than in the
stomach) e.g.

analgesics Drug-induced gastric irritation can

be avoided (due to short residence
time) e.g. aspirin tablets

109. Effervescent tablets usually
contain

Carbonate or
bicarbonate and
a weak acid such
as citric or tartaric,
The amount of
sodium
bicarbonate in an
effervescent
tablet is often
quite high (about
1g)

Flavor and a
colourant

N.B. binder and
disintegrant are
normally not
included in the
composition

A water-soluble
lubricant is
preferable in
order to avoid
a film of a
hydrophobic
lubricant on
the surface of
the water after
tablet
dissolution.

110. ——Effervescent tablets are prepared

by: —

Compaction via
granulation;
traditional wet
granulation is rarely
used.

Direct compaction

| Effervescent tablets
packaging:

They must be protected against moisture by

usin
waterproof containers, often including blister Ser
aluminium foils, otherwise it will be self destructed.

112. 4. Lozenges
* They are tablets that dissolve slowly in the

mouth and so release the drug dissolved in
the saliva.

. They can thus be described as slow-release
tablets for local drug treatment.

Use of lozenges: —
Local medication in the mouth or t
common cola, to treat cough by ==
1.local anesthesia, a
2.antiseptic E
3.antibiotic drugs.

113. Lozenges are usually contain:
1.They are similar in composition to conventional
tablets.

2.Disintegrants are not used.
3.Colour and flavour.

4. High concentration of Fillers which are mainly sugars,
such as glucose, sorbitol or mannitol.

5.High concentration of binder; e.g. gelatin:
Lozenges are prepared by

Compaction at high applied pressures in
obtain a tablet of high mechanical streng
| Porosity which can dissolve slowly in the mouth——

114. 5. Sublingual and buccal tablets

Used for drug release in the mouth followed
by systemic uptake of the drug.

Rapid systemic drug effect can thus be
obtained without first-pass liver metabolism.
Sublingual tablets are placed under the
tongue and buccal tablets are plage
the side of the cheek.

release. ——

115. 6. Soluble tablets

+ Soluble tablets are uncoated or
MISS GRASS HE
water before administration. The___
solution produced may be /
slightly opalescent due to the
added excipients used in the
manufacture of the tablets.

117. <ablet's Testing

This test may be official or unofficial.

Official tests are:
. Weight variation 2. Content uniformity
. Dissolution. 4. Disintegration. „—

Non official tests are:
. Friability .
. Hardness. 3.Thickness .

118. Official Tests
1. Weloht vere

* Collecting a sample of tablets(normally 20)
and determining their individual weights.

« The average weight of the tablets is then
calculated.

e The sample complies with the
standard if the individual weights
don’t deviate from the mean mor
than is permitted in terms of

percentage. =>

119. Ranges in which weigh deviation is
accepted:

weight “à
8 difference

120. If the drug forms the greater part
of the tablet mass, any weight
variation reflects variations in the
content of active ingredients.

correlation between tab
weight and amount of acti L
ingredient can be poor. a

121. « What is the significance of the
weight variation test????

« If tablet batch not pass the test,
what processing factors are th
cause for such Failure?? An
what is the possible solution????

122. C {Weight Variation:

1. The size & distribution of the granules being
compressed (presence of too large or too fine
granules).

2. Poor flow (cause incomplete filling of the die).

3. Poor mixing. (Sometimes the lubricants & glidants
have not been well distributed).

4, When lower punches are of
unequal lengths the fill of each
die varies because the fill is volumetric:
Solution: (Only a good punch & die
control program can provide tooling
of uniform dimensions). Change lubricate à

glidant. E

123. 2, Content Unit ity:

« Determining the amount of drug in a sample of
tablets (10).

« The average drug content is calculated.

« The content of the individual

tablets should fall within

| specified limits in terms of % deviation

repeat using 20 more tablets.

No one should be 75- 125% deviation
Causes: ???

Solution: ????

124. 3. Disint tion:

The test is carried out by:

° Agitating a given number of tablets in an aqueous
medium at a defined temperature & the time to
reach the end-point of the test is recorded.

| + The end-point of the test is the

point which all visible parts of the tablets
have been eliminated from tubes in which
the tablets has been held during agitation.

« The preparation complies with

the test if the time to reach this —

end-point is below given limit; 15-30 minutestor
uncoated immediate release tablets.

125. The disintegration basket

Fig. 2 Schematic of a tablet disintegration apparatus.

126. A disintegration apparatus

127. * Special cases
* Effervescent tablets

« Place 1 tablet in a beaker
containing 200 ml of water at 25°C;
the tablet should evolve bubbles
and disintegrate within 5 mings
use 6 tablets

« Soluble tablets

+ Soluble tablets disintegrate “pale
min when placed in water ar25%€7 |

128. « Sugar coated tablets???

« Enteric coated Tablets????

129. « What is the significance of
the disintegration test???

« If tablet batch not pass the
test, what processing
factors are the cause for
such failure?? And what is
the possible solution???

130. 4. Dissolution:

* Itis an important tool to assess
factors that affect the

bioavailability of a drug from
a solid preparation.

131. Di | ti i i . ] i f | |
reasons.

. To evaluate the possible effect of

formulation & process variables on the
bioavailability of a drug.

. To indicate the performance
of the preparation under in vivo

conditions.

132. * To study the cumulative amount of drug
that passes into solution as a function of
time.

« Locate the tablet in a chamber
containing a flowing dissolution medium.

« All factors that can affect the diss
process must be standardized.
This includes factors that affect
the solubility of the substance i

(i.e. the composition, rotation 8température of
—

the dissolution medium) € E

133. Dissolution tests can be classified into
two main groups:
Stirred-vessel methods.

. Continuous-flow methods.

stirred Vessel Methog

The most important Stirred Vesse F
methods are:

. Rotating-basket method (Appa a:
. Paddle method (Apparatus II).

134. The dissolution test apparatus

135. Paddle Rotating Basket
Method Method
Both use the same type of vessel, which is filled

with a dissolution medium of controlled volume
and temperature.

The tablet is placed in |The tablet is plac o/o
the vessel & the small basket formed
dissolution medium is | from a screen. This is
agitated by a rotating
paddle.

dissolution medium
& rotated at a givers
speed. :

137. Basket type

Paddle type

138. Motor

Solvent (HCL)

Tablet
Paddle

139. « The amount of drug dissolved within a
certain time period is determined by
taking samples from the dissolution
medium and analyzed after specified
time intervals.

« Limit: 75% of the drug should be dissolved
within 30 minutes, unless otherwi

specified by the manufacturer.

140. Unofficial Tests

* Mechanical strength
a. Hardness
b. Friability
c. Thickness

141. 1. Hardness (Fracture-resistance test):
Tablets require a certain amount of
strength or hardness. Why?

1. Withstand mechanical shocks of
handling in manufacture, packaging

and shipping. =
2. Withstand reasonable abuse =
when in the hands of the consumer.

3. The relationship of hardness |
to tablet disintegration, dissolution . ===

142. + Tablet Hardness: The force required to break a
tablet along its diameter by applying compression
loading.

« Test Description:

A tablet is placed between two anvils,
force is applied to the anvils, & the
crushing strength that just causes

| the tablet to break is recorded (in kg).
Hence, Hardness is thus sometimes
termed the tablet crushing strength.

- Tablet hardness should be between
6-10kg

144. Hard Variation:
+ It depends on:
- compression force,

- concentration and type of binding agent

|e If the tablet initially is too hard, it may not
disintegrate in the requisite period of time.

« Ifitis too soft, it may not withstand
the necessary multiple shocks
occurring during handling,
shipping, and dispensing.

+ N.B. Hardness generally increase with
normal storage of tablets.

145. | 3, Can also add to a tablet's weight

2. Friability (attrition-resist test):
It's another measure of a tablet's strength.

Why measure friability?
Tablets that tend to powder, chip &
fragment when handled:

| 1. lack elegance & consumer acceptance,
| 2. Create excessively dirty

processes in areas of manufacturing a
coating & packaging.

variation or content uniformity proble

146. « The laboratory friability tester is known as the

Roche friabilator.

+ It subjects a number of tablets to the

| combined effects of abrasion & shock by

utilizing a plastic chamber that revolves at 25

rom, dropping the tablets with each
revolution.

+ A preweighed tablet sample is
placed in the friabilator, which is
then operated for 100 revolutions.

148. The Roche friabilator

149. Tablets damaged during friability testing

150. ¢ Tablets are then dusted and reweighed.

« Conventional compressed tablets that
lose less than 1.0% of their weight are
generally considered acceptable.

° % friability = (Wo- W;/ Wo) x%. æ
Wo = initial weight. A
W, = final weight.

151. 3. Iablet's Thickness:

e Thickness can vary with no change in
weight due to difference in the density of

the granulation & the pressure applied to
¡the tablets.

+ If the tablets are thicker than

specified, a given number no longer *

may be contained in the volume
of a given size bottle.

152. TABLET COATING

153. What is the rationale for coating a solid
dosage form?

Therapy

+ To minimise irritation of the oesophagus and stomach.
+ Minimise inactivation in the stomach.
+ Improve drug effectiveness.

+ Improve patient compliance e.g. easier to
masks unpleasant taste.

154. What is the rationale for coating a solid
dosage form?

Technology
Minimise dust formation and contamination with respect
to tablets.

Masks batch differences in the appearance q
materials.

Facilitates their handling on high speed autof
and packaging equipment. ae -

Improves drug stability e.g. Protection of a

: a!
from environment such as sunlight, MS me 1

155. What is the rationale for coating a solid
dosage form?

Marketing

+ Aid sales appeal as improved
appearance and acceptability with
respect to gloss and colouration.

+ Mask unpleasant taste.

Improve product identity.

156. Definition

Coated tablets are defined as
tablets covered with one or
more layers of mixture of
various substances with the
intention of (adding) conferring
benefits and properties to the
dosage form over the
uncoated one.

157. coating processes

1. Sugar coating

2. Film coating

3. Press coating

158. |

SUGAR COATING

159. - Sugar coating

Traditionally sugar coatings formed the bulk of coated tablets but today
film coatings are the more modern technology in tablet coating.

Description of tablets: Smooth, rounded and polished to a high gloss.

Process: Multistage process involving 6 separate operations.

1. Seal tablet core
2. Sub coating =
3. Smoothing =_

4. Colouring
5. Polishing
6, Printing

160. Multistage process

1. Sealing tablet core- application of a water impermeable
polymer such as Shellac, cellulose acetate phthalate and
polyvinyl acetate phthalate, which protects the core from
moisture, increasing its shelf life.

2. Sub coating -by adding bulking agents such a coin
carbonate or talc in combination with sucros

SS =

3. Smoothing process -remove rough layers fof
2 with the application of sucrose syrup.

161. Multistage process

Colouring - for aesthetic purposes often titanium based
pigments are included.

Polishing - effectively polished to give
shine, commonly using beeswax, carnauba

Printing -permanent ink for characterization

162. Sugar coating Pans (drum coating)

163. Example of sugar coated tablets

Brufen® POM
— Available in 200mg and
400mg strength

Premarin® POM
— Conjugated oestrogens
625mcg (maroon) and
1.25meg (yellow)

Colofac ® P
— Mebeverine hydrochloride
100mg Round, white,
sugar coated

164. ntation of sugar
coating process

Particle
Coating droplets

Layer build-up

165. + Ideal fan of a

- Perfect smooth rounded countour

- Even colour coverage
- Polish to high gloss

* Coating faults
* Coat splitting caused by inadequat
coat during application

166. Film coating

+ Modern approach to coating tablets, capsules, or pellets by
surrounding them with a thin layer of polymeric material.

+ Description of tablets: Shape dictated by contour of original core.

Process; Single stage process, which involves spraying a coating
solution containing the following;

1. Polymer

2. Solvent

3. Plasticizer

4. Colourant
The solution is sprayed onto a rotating tablet J
by drying, which facilitates the removal o

leaving behind the deposition of thin fil
materials around each tablet.

167. Film coating

Advantages

Produce tablets in a single step
process in relatively short period of
time. Process enables functional
coatings to be incorporated into the
dosage form.

Disadvantages
There are environmental and safety
implications of using organic solvents
as well as their financial expense.

169. Accela Cota

inlet air

spray gun

exhaust air

mixing blades

The vast majority of film coated tablets are produced by a process
which involves spraying of the coating material onto a bed of tablets.
Accela Cota is one example of equipment used for film coating.

170. Film Coating by Fluidized bed |

171. Mechanism of Film Formation

a latex particles dispersed

in liquid vehicle
” —
é ¿9909
CL? TOA
“ . =

172. Examples;

Polymer used in film coating

Cellulose derivatives;
Hydroxypropyl
methylcellulose (HPMC), MC,
HPC, water soluble

- Ethylcellulose is water
insoluble

Methacrylate amino ester
copolymers;
- pH selective polymer

173. Plasticizer used in film coating

- Reduce film brittleness
- Examples;

+ Polyols - Polyethylene glycol
400

» Oils/glycerides - fractional
coconut

oil

174. Colourants used in film coating

Examples;

+» Iron oxide pigments
+ Titanium dioxide
+ Aluminium lakes.

Water insoluble pigments are more fi
water soluble colours for the following reas

Y” Better chemically stability in light
Y” Optimised impermeability to water vapour
v Better opacity
Y” Better covering ability

175. Solvents

Traditionally, organic solvents had been used to
dissolve the polymer but modern techniques rely on
water because of significant drawbacks. Below lists
some of the problems associated with organic
solvents.

+ Environmenta
+ Safety
+ Financial

+ Solvent residues

176. Solvents

1.Environmental

Venting of untreated organic solvent vapour
into the atmosphere is ecologi
unacceptable but removal of gaseo
matter is expensive.

177. Solvents

Safety

Organic solvents are a safety hazard, such that they are:

Toxic

Explosive

Fire hazard

178. Solvents

Financial
The hazards associated with

organic solvents necessitates the
need for building flame- and
explosive- proof facilities. In
addition, the cost of their
storage and ingredients are
relatively expensive.

179. Solvents

Solvent residues

For a given process the amount of residual
organic solvent in the film must be
investigated. Thus, stringent re
controls exist.

180. Ideal characteristics of film-coated tablets

« Even coverage of film and
colour,

« No abrasion of tablet edges,

¢ Logos and break lines should be
distinct and not filled,

+ Comply with the pharmacopeial
requirement.

181. Problems of Film Coating
I * picking/chipping
Ss * roughness
a. * sticking

f 11 « film cracking/peeling p :
ee

182. Film coating
'ablet appearance

Retains shape of original core

Small weight increase of 2-3%
due to coating material

Y logo or ‘break lines’ possible

Process
Can be automated e.g. Accela
Cota

v Easy training operation
Y Single stage process
Y Easily adaptable for controlled

release allows for functional
coatings.

Why is film coating favoured over
sugar coating ?

Sugar coating

Tablet appearance

Y Rounded with high degree of
polish
Larger weight increase 30-50%
due to coating material
Logo or ‘break
impossible
Process
Y Difficult to a
traditional coatin
v Considerable traii
Y Multistage proce
v Not able to be uses
release apart fro:

183. Press coating

core. The technique differs from sugar and film coating process.
Advantages

This coating process enables incompatible materials to be formulated.
that one chemical or more is placed in the core and the other (s)
material.
Disadvantages

Formulation and processing of the coating layer requires some
= A . f . À
complexities of the mechanism used in the compressing equipní

Press coating process involves compaction of coating material around a preformed

tive

184. Functional coatings

Functional coatings are coatings, which perform a
pharmaceutical function.

These include;
+ Enteric coating

» Controlled release coating

185. Enteric coating

The technique involved in enteric coating is protection of the
tablet core from disintegration in the acidic environment of the
stomach by employing pH sensitive polymer, which swell or
solubilize in response to an increase in pH to release the drug.

Protection of active ingredients, from the acidic of

the stomach.
Protection from local irritation of the stomach muc;

Release of active ingredient in specific "oro om al

gastrointestinal tract.

186. -Enteric coating

* An enteric coating is a barrier
applied to oral medication that
controls the location in the
digestive system where it is
absorbed.

« Enteric refers to the small
intestine, therefore enteric
coatings prevent release of
medication before it reaches
the small intestine.

e used for drugs that are
unstable, irritating to stomach

187. Examples of enteric coated OTC products

« Enteric coated aspirin E.g.
Micropirin® 75mg EC
tablets

« Enteric coated peppermint
oil E.g. Colpermin®

188. Summary of Polymers used in pharmaceutical formulations
as coating materials.

Polymer Trade name Application
Shellac EmCoat 120 N o Enteric Coatings, pH 7

Marcoat 125 o targeting to distal small
intestine

ose acetate Aquacoat CPD® | 0 Enteric Coatings
thalate Aquacoat® ECD | o Sustained release coati
o Sub coat

barrier sealant/f

lyvinylacetate Sureteric® o Enteric Coat

phthalate

ethacrylate Eudragit® o Enteric SA
o Sustained Reléase oatings ||

oRapidly disintegrating Films

189. Film coating of Beads and
spheres
« Fluid bed dryer is used