LECTURE 1

by
Ass. Pro. Dr. Mohamed Akl
Assistant professor of Pharmaceutics
 CONTENT..................
❑Introduction
❑General Properties
❑Advantages
❑Disadvantages
❑Types of Tablets
❑Tablet Additives

2
 Introduction
3
 Tablets

 Solid dosage form comprises tablets and capsules

constitute about 80% of all dosage forms.

 They are used to produce systemic action.

 A tablet is a unit dosage form of medication

containing one or more drugs to which excipients are
added and compressed as granules or powder to a
definite shape.
 Advantage of tablet as dosage forms
4
1. Are convenient to use and elegant dosage form.
2. Availability in a wide range of types which offer a range of
drug release rates and duration of clinical effect.
3. Tablets may be formulated to release the drug at particular
site within G.I.T. promoting the absorption at this site. This
could not be done by other dosage forms.
4. Large scale manufacturing is feasible in comparison to other
dosage forms. Therefore, economy can be achieved.
5. Accuracy of dose is maintained since tablet is a solid unit
dosage form.
 Advantage of tablet as dosage forms
5

6. Ease of masking bad taste by coating.

7. Tablets generally are non expensive.
8. Tablets are more stable chemically, physically or
microbiologically than other dosage forms.
9. Formulation of tablets could contain more than one
drug even if there is incompatibility between each
drug.
10. All classes of therapeutic agent may be administered
orally.
 Disadvantage of tablet as dosage forms
6

1. The manufacture of tablets requires many steps of

operation and in each step an increased product loss in
manufacturing.
2. The drug absorption from tablets depends on
physiological factors e.g. gastric emptying rate and
show patient variation.
3. The compression of some drugs into dense compacts is
poor owing to amorphous nature, low density character
→may present problems in the manufacture.
 Disadvantage of tablet as dosage forms
7

1. Drugs with poor wetting, slow dissolution properties, may

be difficult to formulate or manufacture as a tablet that
will still provide adequate or full drug bioavailability.
2. Difficult to swallow in case of children, elderly peoples
and unconscious patients.

 This problem is solved by using effervescent and

chewable tablet.
 General properties of tablet
8

▪ A tablet must be strong and hard to withstand mechanical

shock during manufacturing, packing, shipping, dispensing
and use.
▪ The drug content of the tablet must be bioavailable that is, the
tablet must be able to release its content in a predictable and
reproducible manner.
▪ Must have a chemical and physical stability over time (during
manufacture, storage, and use) so as not to follow alteration of
the medicinal agents
▪ The tablet should have elegant product identity which is free
from any tablet defect (like chips, cracks, discoloration, and
contamination).
▪ Tablets must be uniform in weight and in drug content.
 Different Types of Tablets
9
I. Tablets ingested orally:
▪ Compressed tablet, e.g. Paracetamol tablet
▪ Multiple compressed tablet
▪ Delayed release tablet, e.g. Enteric coated Bisacodyl
tablet
▪ Sugar coated tablet, e.g. Multivitamin tablet
▪ Film coated tablet, e.g. Metronidazole tablet
▪ Chewable tablet, e.g. Antacid tablet
II. Tablets used in oral cavity:
▪ Buccal tablet, e.g. Vitamin-c tablet
▪ Sublingual tablet, e.g. Vicks Menthol tablet
▪ lozenges
▪ Dental cone
 Different Types of Tablets
10
III. Tablets administered by other route:
▪ Implantation tablet
▪ Vaginal or Inserts, e.g. Clotrimazole tablet
IV. Tablets used to prepare solution:
▪ Effervescent tablet, e.g. Dispirin tablet (Aspirin)
▪ Hypodermic tablets: soft, readily soluble tablets
(parental solutions)
 Types of tablets
11

1- Conventional compressed tablets (C.T.)

 These tablets are designed to provide rapid disintegration
and hence rapid drug release and represent a significant
proportion of tablets clinically used.
 These tablets are manufactured by compressing granules
or powders that containing the drug.
 On administration by the patient this tablet will
disintegrate within G.I.T. allowing the drug to dissolve in
the gastric fluid and absorbed.
 Types of tablets
12
2- Multiple compressed tablets (M.C.T.)
 These are tablets composed of at least two layers
 These tablets are prepared by subjecting the fill material
to more than one compression cycle.
 There are two designs;
a- Multiple layered (tablet within tablet)
 tablets composed of two or more layers of ingredients
 In multiple layered tablets, the first layer is formed by
light compression of granules containing the drug then a
next layer of granules containing the drug is compressed
on the first layer.
 Types of tablets
b. – Compression coated (dry/press coated tablet)
 The first layer is prepared by light compression then

removed and located in a second press machine (Manesty

Drycota) to feed granules with drug around the formed
layer (on the surface & edges) then compressed to form a
coated layered tablet.
 The inner tablet being the core and
the outer portion being the shell .
13
 Manesty drycoat
✓ Manesty Drycoat Core and Coating
Tablet Press. Consists of two rotating
Tablet Presses (one used to produce
the core, the other for the coating)
connected by a transfer system.

➢ Operation
1. The tablet core is compressed in the
first turret.
2. Tablet core pass over vacuum to
remover the dust and any granules
then transfer to the turret of the
second press.
3. The tablet core is deposited in the
coating die, coated then compressed.
 core
coat

7 Fig. 7-24. Diagram of

multiple-
compressed tablets.
A, having a core of
one drug and a shell
of another, and
B, a multiple-
layered tablet of two
drugs.
15
 Types of tablets
16

 Application of using the multiple compressed

tablets:
1- Separation of incompatible drug in separate
layered tablet.
2- The delivery of therapeutic agents at different
rates or to different sites within G.I.T. from single
tablet.
3- Production of coated tablets with an external
layer that irritant to the stomach or unstable in
acidic PH.
 Types of tablets
17

3- Enteric coated tablets (E.C.T.)

 They are compressed tablets coated with a polymer that does
not dissolve in acidic conditions (stomach) but dissolve in
alkaline conditions of small intestine (pH 7.4)→ have
delayed-release properties
 The polymers used for enteric coating inhibit the dissolution
of the drug in the stomach or protect the drug (e.g.
erythromycin) from degradation or protect the stomach
mucosa from the irritation caused by some drugs (anti-
rheumatics)
 Types of tablets
18
 Polymers used for enteric coating:
1. Cellulose acetate phthalate (CAP) or cellulose acetate
butyrate, the dissolution of the polymer occurs in solution
above pH 6.
2. Hydroxyl propyl methyl cellulose succinate (HPMCS): this
polymer dissolves in the intestinal secretions.
3. Methacrylic acid co- polymers (Eudragits): it is
characterized by presence of a wide range of functional
groups which exhibit a range of solubility’s.
o Eudragits L100 which soluble in intestinal fluids
from pH 5.5.
o Eudragits S100 which is soluble in the intestinal
fluids from pH 7.
 Types of tablets
19

4- Sugar coated tablets (S.C.T.)

 They are conventional tablets coated with a concentrated

sugar solution to improve the tablet appearance or to

mask bitter taste of the drug.

 Now sugar coated tablets decreased in use for improved

techniques of film coated tablets.

 Types of tablets
20

5- Film coated tablets (F.C.T.)

 These are conventional tablets coated with a polymer or a
mixture of polymers.
 Film coated with polymers that dissolve in stomach (non
enteric) to enable tablet disintegration and dissolution
such as:
1- Hydroxyl propyl methyl cellulose (HPMC).
2- Hydroxyl propyl cellulose (HPC).
3- Eudragit E100.
 Types of tablets
21

 If the film coating is employed to control the rate and

duration of drug release in certain region of G.I.T, the
drug release occurs by diffusion through the insoluble
coating and subsequent partitioning into G.I.T fluids.
 Examples of polymers used for this purpose:
1- Ethyl cellulose (EC)
 It is insoluble in aqueous solutions at all pH values.
 2- Eudragit RS and RL:
 Are methacrylate co- polymers that are insoluble in water. The
RS differs from RL in the ratio of monomers.
 Types of tablets
22
6- Chewable tablets
These are big sized tablets which are difficult to swallow
and thus, are chewed within the buccal cavity prior to
swallowing and applied mainly for:
 Administration to children and adults who have difficulty
in swallowing conventional tablets.
 Antacid formulations in which the and the neutralization
efficacy of the tablet is related to particle size within the
stomach. e.g., magnesium trisilicate tablet
❑ If the drug taste is not acceptable, it is not recommended to
be manufactured in chewable tablet.
 Types of tablets
23
7- Effervescent tablets
 They are tablets when added to aqueous
solutions → they will rapidly disintegrate with
eff producing solution or suspension of the drug in aqueous medium.
 contain organic acids (such as tartaric or citric acid) and sodium bicarbonate
in addition to the medicinal substance or API.
 The disintegration of the tablet is due to a chemical reaction occurs between
two component in the presence of water, with the evolution of CO2 which
causes the disintegration.
 This type of tablets has the advantage of producing a solution ready for
absorption in G.I.T.
 The main disadvantage is the need of a moisture impermeable package such
as aluminum foil to inhibit the interaction between the acid and sodium
bicarbonate.
 Types of tablets
24
8- Buccal and sublingual tablets:
 Small, flat, oval tablets that are held within oral cavity and
slowly dissolve.
 The drug is absorbed across the buccal mucosa to
produce systemic effect.
 Buccal tablets are placed between the cheek (‫ )الخد‬and
the gingival (‫ )اللثة‬while the sublingual tablets
(glyceryl trinitrate) are placed under the tongue.
 These tablets are employed to achieve either rapid
absorption & avoiding first pass metabolism or for drugs that are
destroyed by the gastric juice and/or are poorly absorbed from the GIT.
 Buccal and sublingual tablets should be formulated to dissolve slowly in
vivo and not disintegrate with retaining in the site of application.
 It should not contain components that stimulate the production of saliva.
 Types of tablets
25
9- Lozenges tablets:
 These are disc-shaped solid preparations containing medicinal agents and
generally a flavouring substance in a hard candy or sugar base.
 They are intended to be slowly dissolved in the oral cavity, usually for
local effects.
 Example: Strepsils ® Dry Cough Lozenges
 Types of tablets
26

10- Vaginal tablets

 These are uncoated ovoid shaped tablets that are inserted into the
vagina using a special inserter.
 They are prepared by compression and are shaped to fit tightly on
plastic inserter devices that accompany the product
 Following insertion → retention and slow dissolution of the tablet
occur → release the therapeutic agent to provide local therapeutic
effect, e.g. for the treatment of bacterial or fungal infection.
Vaginal tablets may also be used to provide systemic
absorption of the drug.
 It is essential that dissolution & not the disintegration of the tablet
occurs in vivo.
 Types of tablets
27

11. Implantation Tablets/ Implants

 These are long-acting sterile tablets designed to provide
continuous release of drugs, often over a period of months
or a year.
 They are placed subcutaneously for systemic or local
delivery.
 Implants are mainly used for the administration of
hormones for contraception.
 They usually contain rate-controlling excipients in
addition to the active ingredient(s).
 Manufacture of tablets
28

 In this important section we will explain the following:

1- Excipients used in the manufacture of tablets
2- Methods used for the manufacture of tablets
1- Excipients used in the manufacture of tablets:
 The following excipients are used in the manufacturing of
the conventional tablets:
1- Diluents = fillers = bulking agents
2- Binders
3- Disintegrants
4- Lubricants 5- Glidants
6- Miscellaneous
29
 Excipients used in the manufacture of tablets:
Excipient Role
30 Example
Diluents Diluents increase the volume to a formulation to • Lactose
prepare tablets of the desired size. Widely used • Dextrin
as fillers • MCC

Binders Promote binding the particles of the formulation • Starch

and make them cohesive during direct • Gelatin
compression and ensure the tablet remaining • [Link]
intact after compression
Lubricants Substance that preventing the adhesion of the • Glycerylmo
tablet material to the dies and punches. It works nostearate
by coating on the surface of particles. • [Link]
Glidants Substance that is added to improve powder • Talc
flowability. • Starch
Disintegrant Agents added to tablet formulations to promote • Starch.
it is breakup into smaller fragments in an • SAA
aqueous environment thereby increasing the • Alginic acid
available surface area and promoting a more
 Tablet Ingredients
31
1- Diluents = fillers = bulking agents
 They are employed in tablet formulation by any method to increase
the size of the tablets to get a significant tablet weight that can be
handled or compressed, thereby rendering the manufacturing process
more reliable and reproducible.
 Tablets weigh normally at least 50 mg, therefore a low dose of a
potent drugs requires addition of a filler to increase the bulk volume
of the powder and hence the size of the tablet.
 Diluents must
1. exhibit good compression proprieties and not expensive
2. They should be physiologically and chemically inert,
3. non-hygroscopic, hydrophilic (water soluble)
4. Have an acceptable taste
1- Diluents = fillers = bulking agents
32
Lactose possesses many good filler properties:
➢ Anhydrous lactose:
 Is available in a range of particle sizes & used mainly as diluents in
wet granulation & dry granulation. It is a crystalline material.
➢ Lactose monohydrate:
 It is available in a wide range of grades with different physical
properties e.g.: particle size & bulk density.
➢ Spray dried lactose:
It is a mixture of crystalline α-lactose monohydrate (80- 90 %) &
10-20% amorphous lactose. It is prepared by spray drying a
suspension of α-lactose monohydrate. The specific use of spray dried
lactose for the manufacture of tablets by direct compression method.
1- Diluents = fillers = bulking agents
33
➢ Mannitol:
 It is a polyol used as diluents specially for chewable
tablets due to its sweetness (imparts a cooling sensation
when chewed). It has excellent flowability.

➢ Starch:
 It is a polysaccharide composed of amylose &
amylopectin used as diluent, binder & disintegrants.
 Pregelatinized grade is available in which the granules of
starch physically & chemically modified to produce free
flowing powder (granular starch)
1- Diluents = fillers = bulking agents
34

➢ Microcrystalline cellulose ( MCC): Avicel®

 It is crystalline powder prepared by controlled hydrolysis of
cellulose. Different grades are present that differ in physical &
chemical properties such as density, flow properties & particle size
distribution. E.g.: Avicel PH- 101 (powder) & Avicel PH- 102
(granular).
 Also, used as dry binders and disintegrants
➢ Dibasic calcium phosphate:
 It is available as different hydrate forms with range of particle sizes.
It is a basic excipient & may react with acidic component in
presence of moisture. It has an excellent flow & compression
properties.
 Selection of diluent
35

 Based on the experience of the manufacturer as well as on

the cost of the diluent and its compatibility with the other
tablet ingredients, the proper diluent could be chosen.
1. Calcium salts can not be used as fillers for Tetracycline
products because calcium interferes with the absorption of
Tetracycline from GIT.
2. When drug shows low water solubility, it is recommended
that water soluble diluents be used to avoid possible
bioavailability problems.
3. The combination of amine bases and salts with Lactose in
presence of alkaline lubricant results in discoloration upon
ageing.
 2. Binders (Adhesive, granulators)
36

Role:
→impart cohesive qualities to powdered materials used in
tablet manufacture →
 To bind powders together in the wet granulation process
 To bind granules together during compression
Example of commonly used binders:
1. Solution binders as starch, sucrose and gelatin.
2. Dry binders as microcrystalline cellulose and cross
linked PVP
❑ The binding action is more effective when the binder is in
a solution form than if it was dispersed in a dry form and
moisten with the solvent.
 Types of binders

sugars Polymeric materials

Natural polymers Synthetic polymers

Starches, gums and Methyl, ethyl, hydroxypropyl
gelatin cellulose and pvp.

37
 38

 Different used binders

Name Conc. Solvent
used
1. Starch 5-10% Aqueous paste
2. Pregelatinized starch 5-10% Added dry to powder
3. Gelatin 2-10% Aqueous solution
4. Polyvinyl pyrrolidon 5-10% Aqueous alcoholic solution
5. Methyl cellulose 2-10% Aqueous solution
6. Sod. carboxy methyl 2-10% Aqueous solution
cellulose
7. Ethyl cellulose 5-10% Alcohol or hydro alcoholic solution
8. Poly Vinyl alcohol 5-10% Aqueous solution
Different Ways to add a Binder:
39
1. Solution binder
 As a dry powder which is mixed with the other ingredients
before wet granulation.
 Mechanism of action: During the granulation procedure
the binder dissolves partly or completely in the liquid; as a
solution which is used during wet agglomeration.
2. Dry binder
As a dry powder which is mixed with other ingredients
before compaction.
Both binders are included in the formulation at low
concentrations, 2 – 10 %.
N.B. The use of excessive binder → will make a hard tablet that will
not disintegrate easily when the tablet meets moisture and will
also cause excessive wear of punches and dies.
 40
3- Disintegrants
 They are employed to overcome the cohesive strength
imparted during compression → facilitate the breakdown
of the tablet granules upon entry into the stomach.
 The disintegrant is essential in hydrophobic tablets with
high compression force to enable disintegration within
the pharmacopeia standards (15 minutes for conventional
tablets)
3- Disintegrants
41
 3- Disintegrants
42
Mechanisms of disintegration:
1. Swelling:
▪ Croscarmellose sodium, swell in contact with gastric fluids and
exert sufficient mechanical pressure within the tablet, the
adhesiveness of other ingredients in a tablet is overcome →
causing the tablet to break apart into small segments and thus
hasten the absorption by increasing surface area of particles.
 3- Disintegrants
43
Mechanisms of disintegration:
2. Porosity and Capillary Action (Wicking):
 Disintegrants may increasing the porosity and wettability of the
compressed tablet matrix → provides pathways for the
penetration of fluid into tablets → Liquid is drawn up into these
pathways through capillary action and rupture the inter-particulate
bonds causing the tablet to break apart.
❑ These disintegrants are mainly hydrophilic polymers.
❑ Examples: The most traditional disintegrant in conventional tablet
is Starch (10%)
❑ Super-disintegrants (1.5 %); e.g. Sodium Starch Glycolate that
swells 7-12 fold in less than 30 sec. e.g. Croscaramelose that
swells 4-8 fold in less than 10 sec
 3- Disintegrants
44

Notes
 Disintegrants may be added intra- or, extra-granularly or both

(which may be varied to achieve the best result).

 It does not always mean that the higher the concentration of

disintegrants the faster the rate of disintegration.

 The concentration may have a direct relationship with the rate of

disintegration until it gets to maximum after which disintegration

rate decreases with increase in concentration of disintegrants.
4- Glidants
45
 Like lubricants, they act to enhance the flow properties of tablet
granules or powders within the hopper by reducing friction between
particles → is due to the ability of glidants particles to locate within
the spaces between the powder particles/ granules.
 To achieve this effect the Glidants must be small in particle size and
to be arranged on the surface of the granules.
 Their concentration must not exceed the recommended as it is
hydrophobic & may affect the disintegration of the tablet and the
dissolution of the drug.
 Examples:
1. Traditional glidant is Talc (0.5- 3 % w/w)
2. most common glidant today is Colloidal silicon dioxide (0.1 - 0.5
% w/w)
5- Lubricants 46
 Lubricants reduce the friction occurs between the walls of the
tablets and the walls of the die cavity and punches during
compression facilitate the ejection of the tablets from the die cavity.
 Insufficient lubricant will lead to tablet, with a pitted‫ محفور‬surface
 where high conc. of lubricant → will lead to reduced disintegration
and dissolution.
 In addition, the time of mixing of lubricant with granules as well as
the particle size of the lubricant will affect the performance of the
lubricant. → Over mixing may adversely affect tablet disintegration
& drug dissolution.
 Lubricants should be added after disintegrants to avoid coating it or
preferably at the final stage prior to compression to ensure mixing
time is kept to a minimum
5- Lubricants 47

 Mixing of disintegrant & insoluble lubricant together should be

avoided for this should form a film of lubricant on the
disintegrant surface which reduce wettability of disintegrant
 There are 2 main categories of lubricants:
1- Insoluble lubricants:
 They are added to the final mixing stage before tablet
compression.
 The efficacy of lubricant is enhanced if its area is increased
(decrease the particle size).
 Examples of insoluble lubricant material:
1. Magnesium stearate (0.25 - 0.5 % w/w)
2. Stearic acid (1 – 3 % w/w)
5- Lubricants 48

2- Soluble lubricants:

 They are used to overcome the bad effects of insoluble

lubricant on the tablet disintegration & drug dissolution,

although the effect of insoluble lubricant is superior than the
soluble lubricants. Examples:

 1. PEG 4000, 6000 or 8000 grades.

 2. Sodium lauryl sulfate 1- 2 % w/w.

6- Miscellaneous excipients
49

(1) Adsorbents
 They are included to be adsorbed a liquid or semisolid
component (e.g., flavour) when incorporated within the
tablet formulation.
 Examples: Magnesium oxide or carbonate and kaolin or
bentonite.
(2) Sweetening agent / flavors
 They are incorporated to control the taste and tablet
acceptability especially chewable tablets if the
components have disagreeable taste.
6- Miscellaneous excipients
50
(3) Colors
 They are used to improve the tablet appearance or to identify the
finished product.
 The color must be distributed well throughout the tablet by
adding a water soluble color to the granulation liquid in wet
granulation method.
(4) Surface active agents
 They are added to improve the wetting properties of hydrophobic
tablets → increasing the rate of tablet disintegration.
 Also they are added to increase the solubility of poorly soluble
drug in G.I.T hence increasing the rate of tablet dissolution e.g:
Sodium lauryl sulfate.
 Methods used for the manufacture of
tablets
51

 Tablets are commonly manufactured by one of the following processes:

I. Wet granulation: wet method (Discuss In Granulation)
II. Dry granulation or slugging or roller compaction (Discuss In
Granulation)
III. Direct compression
 The choice of manufacture method is dependent on these factors:
1. Physical and chemical stability of the drug during
manufacturing.
2. The availability of the necessary processing equipment.
3. The cost of manufacturing process.
4. The excipients used to formulate the product.
Tableting methods

52 52
 Granulation

What is the granulation?

➢ It is defined as a size enlargement process whereby

small primary powder particles are made to adhere

to form larger, multiparticle entities called granules.

 Why we prepare granules when
we have powders….?
1. Powder not flow well in the hopper of the tablet machine.
2. Powder do not flow uniformly in the die, which leading to
variation in tablet weight.
3. Air trapped in the powder, which causes lamination or
capping of tablet when the pressure is released

CAPPING: It is partial or complete separation of the top or

bottom of tablet.

LAMINATION: It is separation of tablet into two or more

layers.
LAMINATION
 Reasons for granulation
56

1. To prevent segregation of the constituents of the powder mix

2. To improve the flow properties of the mix
3. To improve the compaction characteristics of the mix
4. Other reasons
o Reduce the hazard of toxic dust powders (dust free
formulations).
o Reduced caking and lump formation
o More convenient for storage.
 Reasons for granulation
57

1. To prevent segregation of the constituents of the powder mix

A. Segregation is due primarily to differences in the size or

density of the components of the mix,

 The smaller and/or denser particles concentrating at the base

of a container, while the larger and/or less dense ones above

them.

 An ideal granulation will contain all the constituents of the

mix in the correct proportion in each granule, and segregation

of the ingredients will not occur (Fig. 1).
 58

58
 Reasons for granulation
59

B. Control the particle size distribution of the granules because if

there is a wide size distribution the granules themselves may
segregate.

If this occurs in the hoppers of sachet filling machines, capsule

filling machines or tablet machines, products with large weight
variations will result. This will lead to an unacceptable
distribution of the drug content within the batch of finished
product.
 Reasons for granulation
60

2. To improve the flow properties of the mix

⚫ Many powders, because of their small size, irregular shape or
surface characteristics, are cohesive and do not flow well.

⚫ Poor flow will often result in a wide weight variation within the
final product owing to variable fill of tablet dies etc.

→ Granules produced from such a cohesive system will be larger

and more iso-diametric, both factors contributing to improved flow
properties.
 Reasons for granulation
61

3. To improve the compaction characteristics of the mix

⚫ Some powders are difficult to compact even if a readily

compactable adhesive is included in the mix, but granules of the
same formulation are often more easily compacted and produce
stronger tablets. This is associated with the distribution of the
adhesive within the granule.
 Other Reasons for granulation
62

i. Reduce the hazard of toxic dust powders.

⚫ The granulation of toxic materials will reduce the hazard
associated with the generation of toxic dust that may arise when
handling powders.
ii. Reduced caking and lump formation, as in the granulation of
fertilizers.
⚫ Materials which are slightly hygroscopic may adhere and form a
cake if stored as a powder. Granulation may reduce this hazard, as
the granules will be able to absorb some moisture and yet retain
their flowability because of their size.
iii. More convenient for storage.
⚫ Granules, being denser than the parent powder mix, occupy less
volume per unit weight. They are therefore more convenient for
storage or shipment.
 Methods of granulation
63

Granulation methods can be divided into two types:

1. Wet methods, which use a liquid in the process, and

2. Dry methods in which no liquid is used.

 Dry Granulation
64

• Dry granulation converts primary powder particles into granules

using the application of pressure without the intermediate use of a
liquid.
• It therefore avoids heat-temperature combinations that might
cause degradation of the product.

Two pieces of equipment are necessary for dry granulation:

─ first, a machine for light compressing the dry powders blend into
compacts or flakes, under low pressures
─ secondly a mill for breaking up these intermediate products into
granules.
Steps in Dry Granulation

Compaction of powder

Milling

Screening
65
 When To Choose DRY method?
66

❑ Drug dose is too high.

❑ Do not compress well after wet granulation as calcium lactate
❑ Heat sensitive drugs.
❑ Moisture sensitive drugs. e.g. Aspirin , Vitamins
❑ For improved disintegration since powder particles are not
bonded together by a binder.
67
 Dry granulation
68

❑ In the dry methods of granulation, the primary powder particles are

aggregated under high pressure.
❑ There are two main processes.
1. Either a large tablet (known as a 'slug') is produced in a
heavy-duty tabletting press (a process known as 'slugging') or
2. The powder is squeezed between two rollers to produce a sheet of
material ('roller compaction’).
❑ In both cases these intermediate products are broken using a
suitable milling technique to produce granular material, which is
usually sieved to separate the desired size fraction.
❑ The unused fine material may be reworked to avoid waste.
 1. Sluggers
69
Steps in dry granulation (Slugging) :
1. Compression of finely divided dry powders into large, hard tablets (slugs)
using a conventional tablet machine or, more usually into the dies of a
large capacity tablet press and compacting by means of flat faced punches.
2. Screening of slugs, a hammer mill is suitable for breaking the compacts.
❑ Slugs is typically 25 mm diameter by about 10-15 mm thick.
❑ The slugging process is still used today by only a few manufacturing firms
that have old pharmaceutical formulation processes.
Disadvantage:
This method cause weight variation from one tablet (slug) to another due to a
small particle size do not flow well into the die of a tablet pres
 1. Sluggers

❑ These are heavy-duty tablet presses that are fitted with punches
and dies of about 1 inch in diameter.
❑ Pressures up to 20.000 p.s.i. can be exerted.
 2. Roller Compaction (Chilsonator)
71
 Roller compaction is an alternative gentler
method, well suited for dry granulation in the
area of modern development of active
pharmaceutical ingredients
 The powder mix being squeezed between two
rollers to form a compressed sheet (Fig. 2).
 The sheet normally is weak and brittle and
breaks immediately into flakes.
 These flakes need gentler treatment to break
them into granules, and this can usually be
achieved by screening alone.
 It used for material that normally require
slugging two or more times, so it can be
granulated by passing single time through
“chilsonator” .
 2. Roller Compaction (Chilsonator)
72

➢ Steps
1. A feeding system, powders are fed from a hopper which contains a spiral
screw, → conveys the powder to the compaction area between the 2 rotating
rollers.
2. A compaction unit, where powder is compacted between two rotating rolls to
a ribbon by applying a force at a controlled rate and pressure regulate by
hydraulic means.
3. A size reduction unit, the product obtained in the form of compressed sheets,
which can be broken up in to granules of the desired particle size.
 2. Roller Compaction (Chilsonator)
Notes:
• The pressure between the rolls is regulated by hydraulic means.
• The screw serve to maintain a constant flow of the powder into the
compaction rolls.
 2. Roller Compaction (Chilsonator)

Advantages chilsonator over slug processing

1. Increased production capacity
2. Greater control of compaction
pressure, and
3. No need for lubrication of the
powder.

74
 Advantage and Disadvantage of Dry granulation

Disadvantages
Advantages
o It requires a specialized heavy
• We used conventional duty tablet press to form slug.
grades of excipients.
o No uniform color distribution
• Less equipment & space
o 2. Segregation may occur post
• Eliminate need of binder mixing.
solution, heat or heavy
mixing equipment and time o The final tablet produced by
consuming drying step dry granulation tends to be
required for wet softer than these of wet
granulation granulation rendering them
difficult for further process
such as coating.
o Process create more dust,
increasing the potential
contamination
 2. Wet Granulation
76

1. The granulating fluid contains a solvent which must be

• volatile so that it can be removed by drying, and be
• non-toxic.
• Typical liquids include water, ethanol and isopropanol, either
alone or in combination.
2. The granulation liquid may be used alone or, more usually, as a
solvent containing a dissolved adhesive (also referred to as a
binder or binding agent) which is used to ensure particle
adhesion once the granule is dry.
o Natural Polymers: Starch, Pregelatinized Starch.
o synthetic binders: PVP, MC, HPMC, Maltrodextrin
 Water is commonly used for economical and
ecological reasons.
77

Disadvantages of water as a solvent are:

A. It may adversely affect drug stability, causing
hydrolysis of susceptible products, and

B. It needs a longer drying time than do organic

solvents.

This increases the length of the process and

again may affect stability because of the
extended exposure to heat
 Advantage of water:
78

 It is non-flammable, which means that expensive safety

precautions such as the use of flameproof equipment are not
needed.

 Organic solvents are used when water-sensitive drugs are

processed, as an alternative to dry granulation, or when a rapid

drying time is required.

 In the traditional wet granulation method the wet mass is forced

through a sieve to produce wet granules which are then dried.

 I. Wet granulation
79
 Important steps involved in the wet granulation
• The active ingredient and excipients are weighed and
1 mixed.
• The wet granulate is prepared by adding the liquid binder–
2 adhesive to the powder blend and mixing thoroughly

• Screening the damp mass through a mesh to form pellets

3 or granules
• Drying the granules through conventional tray-dryer or
4 fluid-bed dryer.
• After the granules are dried, they are passed through a
screen of smaller size than the one used for the wet
5
mass to create granules of uniform size
 Important steps involved in the wet granulation
80

Step 1
 Mixing the therapeutic agent with the powdered
excipients (without lubricant)
 Using a mixer for a sufficient specified time and speed
till become homogenous.

Step 2
 Wet granulation of the powder mix to make
homogenous granules (0.2 - 4 mm diameter)
 Important steps involved in the wet granulation
81

 Description of wet granulation

1. To achieve cohesion between powders: we use a binder
within the formulation either in the solid state within the
powder mix or dissolved in the binding fluid (water,
isopropanol or ethanol) the wetted mass is then passed
into an oscillating granulator which forces the wet mass
through a metal screen under the action of an oscillatory
stress.
 Important steps involved in the wet granulation
82

2. Achieving wet granulation using high speed mixer/

granulator:
 This is more recent as in this machine single operation is
employed. e.g: high shear (speed) mixer
3. Using fluidized bed drier for granulation and drying. This
system of operation includes 3 steps in one operation.
■ Mixing of powder ,
■ Spraying the binder solution within mixing ,
■ Applying hot air (controlled temperature) → the solvent
will evaporate and the formed granules will be dried.
 Important steps involved in the wet granulation
83

 Advantages of granulation step in tablet manufacture

1. Prevention of segregation of powder component during
manufacture process.
2. Enhancement of the flow properties from the tablet
hopper to tablet dies in the machine to prevent the
variability in tablet weight.
3. Enhancement of the compaction properties due to the
presence of binder on the surface of granules leading
to greater intergranule adhesive interactions.
4. Lower incidence of dust production.
 Important steps involved in the wet granulation
84

Step 3
 Drying of the granules:
The produced wet granules are dried in the shelf or tray drier
which is similar to the design of conventional oven.
Step 4
 Milling of the granules: reduction of the granule size to:
a) Controlling the particle size to improve the flow of granules
into the tablet die and the fill of granules within the die.
b)The choice of the granule size is determined by the size of the
die & hence the final tablet size.
 The reduction of the granule size is performed by using:
1. Oscillating granulator 2. Using Quadro-Co mill.
 Important steps involved in the wet granulation
85

Step 5
 Mixing of granules with lubricant:
Mix the dried and milled granules with the specified
quantity of the lubricant before feeding to the tablet
press hopper.
Wet granulation
86
 Advantages and disadvantages of wet
granulation method
87

 Advantages:

1. Reduced segregation of the component during

processing.

2. Useful technique for the manufacture of tablets

containing low concentration of therapeutic agents.

3. Employs conventional excipients [Link] dependent

on special excipients such as direct compression
method.
 Disadvantages:
88

1. Several proceeding steps are required increase the time ,

loss of material and effort.
2. It is not used with heat and/or moisture – sensitive
material.
3. Solvents are required in this process; this may lead to
different problems such as:
a. Drug degradation may occur in the presence of the
solvent.
b. Drug may be soluble in the granulation fluid.
c. Heat is required to remove the solvent; → this could result
degradation of the thermally labile therapeutic agents.
 Disadvantages:
89

4. Cost is high because of long procedures and use number

of expensive equipments.
5. It requires a large area with temperature and humidity
control as it require many steps.
➢ Tablet manufacturing methods
Wet granulation: suitable for drugs that are stable to
Granulation moisture and heat

Dry granulation: suitable for drugs that are sensitive to

moisture and heat
Powder compression : suitable for drugs that are sensitive to
Direct moisture and heat, fill material possessing good flowability
compression and compressibility

Crystal compression：suitable for drugs with proper

crystal form and good flowability
• Tablet machine:
a. single-punch Tablet machine
b. multi-station rotary presses (rotary tablet)
 1. single-punch tablet machine

✓ The basic mechanical parts of single-punch tablet machine:

1. Stationary Die fitted with upper and lower punch.

o Upper punch is out of the die, while the lower punch is at the
lowest position of die.
2. Movable feed hopper
3. Feed shoe connected to the movable hopper
 Main part and it is function
1 Die The die cavity is where the powder granules are compressed
into tablet by allowing the lower and upper punch to come
close together to compress the material.
The die determines;
1. The diameter of the tablet
2. The size and shape of the tablet
3. To some extent the thickness of the tablet.
2 Upper punch Form the upper surface of the tablet
3 Lower punch Form the lower surface of the tablet
It control the weight of tablet by controlling the size of the
die cavity
4 Feed shoe Connect the hopper to the die
5 Hopper This is connected to the feed shoe and it is used to hold
the materials (drug or the drug with excipients/
granules) to be compressed and supply the material to
the die and removes the tablet after its compression. It
can be filled manually or by using mechanical equipment
93tableting.
during subsequent
1. single-punch tablet machine
 ❑ The Compression cycle of a single Punch tablet machine
Filing

Position 1 – The upper punch is raised and lower punch drops to create a cavity
in the die.
Position 2 – Feed shoe moves over the die cavity and granules fall into the die
cavity under the influence of gravity from the hopper.

Compression

Position 3 – Feed shoe moves out of the way and the upper punch descends to
compress the granules/powder mixture into tablets by progressive reduction of
the porosity of the die content and forcing of the particles into close contact with
one another.

Ejection

Position 4 – The upper punch retracts and the lower punch moves upwards too to
form the lower surface of the tablet then the feed shoe eject the compressed
tablet. The whole events repeat over and over again unit the feed material is
exhausted.
Stages of tablet formation
➢ The high to which the lower punch rises is adjustable because of:
✓ If too low the feed shoe would split or cap the tablet during ejection.
✓ If too high feed shoe strike the lower punch with mutual damage
1. The single punch structure is rational and small.
2. Easy to operate and it operates at a high utilization ratio.
3. The compression time is very short.
4. It can manufacture odd shaped products with a diameter of up to 20
mm.
5. It is ideal for development of tablets and small batch production (100
tab/ min).
6. Single punch tablet press utilizes a high amount of pressure to reduce
weight variations between tablets while maintaining a low noise level at
the same time.
 2. Rotary tablet machine
➢ Rotary tablet machine (Multi-station press) is a mechanical device that unlike
the single punch tablet press has movable die and stationary feed hopper
➢ Multi-station press are also referred to as rotary tablet press because it is about
circular rotating head carrying an :
• the upper punches in the upper part
• The dies ( ≥ 60 dies ) in central part with the feed frame placed over it.
• The lower punches in lower part.
➢ Rotary press employs the principle of compression.
➢ This tableting machine was developed to increase the output of tablets (up to
10000 tablet / minute).
 hopper
feed-frame

head: upper turret, lower turret, die table

upper turret
die table
lower turret
 ❑ The Compression cycle of a rotary tablet machine
Filing

➢ The head revolve, the die come under the feed frame and filed with granules.

Compression

➢ The upper and lower punch pass between rollers and compress the granules
as follow:
o The upper punch is in raised position and lower punch drop to the lowest
position
o The upper punch descend to enter the die cavity and lower punch pass
between roller then compress the tablet.

Ejection

➢ The upper punch to it is raised position and lower punch rises to completely
eject the compressed tablet. The whole events repeat over and over again unit
the feed material is exhausted.
Rotary tablet press
 ❑ Advantages of Rotary Tablet machine

1. High productivity can be gained with a minimal number of labor while saving
money.
2. Rotary press has an output of between 9000 – 234000 tab/hour thus saves
time and meets up with the high demand of tablet dosage form.
3. The powder filled cavity can be automatically managed by a moving feeder.
4. Rotary press decreases waste of valuable formulation in non-specific tablets.
5. The machine allows independent control of both weight and hardness.
 Quality Control Tests
of pharmaceutical dosage forms
Manufacturing problems
1. 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.
2. Sticking, Picking & Filming:
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.
❑ Picking : (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.
2. Sticking, Picking & Filming:
❑ Filming: is a slow form of sticking and is
largely due to excess moisture in the
granulation, high humidity, high
temperature, or loss of highly polished
punch faces due to wear.

These may be overcome by:

1. Decreasing the moisture content of the granulation.
2. Polishing the punch faces.
3. Cleaning and coating the punch faces with light mineral oil
3. Capping & Laminating:

o These two defects occur during the ejection

stage of the manufacturing process.
❑ Capping occurs when the upper segment of
the tablet separates from the main portion of
the tablet & comes off as a cap.
▪ It is usually due to air entrapped in the
granulation that is compressed in the die
during the compression & then expands
when the pressure is released.
• 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
3. Capping & Laminating:
❑ 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.

❑ Solutions for capping & laminating:

1. Increasing the binder.

2. Adding dry binder such as gum acacia, PVP or powdered sugar.
3. Decreasing or changing lubrication.
4. Decreasing the upper punch diameter
4. Mottling:
▪ It is an unequal distribution of color on the surface of the tablet with
light or dark areas standing out in an otherwise uniform surface.
• Reasons of Mottling :
1. A drug is differs in color from its excipients or whose degradation
products are highly colored.
2. Migration of a dye during drying of a granulation.

To overcome this difficulty,

▪ The formulator may change the solvent system, reduce the drying
temperature, or grind to a smaller particle size.
5. Chipping and Cracking:
❑ Chipping: Breaking of tablet edges, while the tablet leaves the press
or during subsequent handling and coating operations.
❑ Reasons of Chipping
1. Incorrect machine settings, specially mis-set ejection take-off.

2. These problems are similar to those of capping and laminating, and

are annoying and time consuming.
❑ Cracked tablets are usually cracked in the
upper and lower central surface of the
tablets or very rarely on the side wall.
❑ different from capping.
Causes:
• It often occurs where deep concave
punches are used.
• Large size of granules
• Too dry granules
• - tablets expanding

Solutions for Chipping & Cracked :

1. Polishing punch faces.
2. Replacing nicked or chipped punches.
3. Reducing fines.
4. Adding dry binder such as pregelatinized starch, gum acacia,
PVP,
Tablets evaluation
Evaluation of tablets includes:
1- General appearance
2- Weight variation
3- Friability
4- Disintegration test
5- Dissolution rate
6- Hardness
7- Content uniformity
8- Thickness
1- General appearance
Size, shape, and thickness:
This is important to facilitate packaging and to decide which
tablet compressing machine to use.
-Organoleptic properties:
which include color, taste and odor of the tablets
2. Weight variation
- To ensure that the tablet formulation is uniform in
weight.
- Weight variation test is applicable when the tablets
containing 50 mg or more of drug substance or when the
drug substance represents 50% or more (by weight) of the
dosage form unit.
1. Twenty tablets are dusted and weighed.
2. The average weight (Mean) is calculated (X).
3. Each tablet is then weighed individually .
4. Calculate the % of deviation for each tablet
according to the Formula.
- % Deviation = [(weight of tablet – mean) / mean ] X
QC of dosage forms
100
Weight variation:

- According to USP, B.P The batch accepted when :

❑ Not more than 2 tablets are permitted to deviate from the average
weight by greater than the permissible deviation listed.

❑ No tablet is permitted to deviate from the average weight by more

than double deviation

Notes :

o The test not carried out for coated tablets due to the content of
coating materials are not calculated.

o The test indicates the uniformity of drug content if the drug content
is more than 50 mg QC of dosage forms 122
 USP 32 B.P
Average weight % Average weight %
mg Deviation mg Deviation

120 mg or less ± 10 130 mg or less ± 10

>120 mg to < 300 mg ± 7.5 >130 mg to < 324 mg ± 7.5

300 mg or more ±5 324 mg or more ±5

QC of dosage forms 123

123
⦿ Limit:
⦿ Upper limit = average weight + (average weight * %error)
⦿ Lower limit = average weight - (average weight * %error)
⦿ The individual weights are compared with the upper and
lower limits.
>>Not more than two of the tablets differ from the average
weight by more than the % error listed, and no tablet differs
by more than double that percentage.
Tablets that are coated are exempt from these
requirements but must conform to the test for content
uniformity if it is applicable.
 Problem 1
Solve the following
• The tablet below provides the weight of each of 20 tablets sampled
during drug production for in-process weight variation test (tablet
specified weight is 300 mg). Guided by the USP, state whether this
given batch will be accepted or rejected.
• Justify your answer.

Tablet 1 2 3 4 5 6 7 8 9 10
Weight
286 305 311 300 307 290 310 314 311 304
(mg)

Tablet 11 12 13 14 15 16 17 18 19 20

Weight
301 299 309 289 295 301 287 313 291 307
(mg) QC of dosage forms 125
 Solution
Tablet 1 2 3 4 5 6 7 8 9 10
Weight (mg) 286 305 311 300 307 290 310 314 311 304
Tablet 11 12 13 14 15 16 17 18 19 20
Weight (mg) 301 299 309 289 295 301 287 313 291 307

Average Percentage of Lower limit of Upper limit of

weight deviation deviation deviation
300 mg 5% 285 315

Double limit of Double lower limit of Double upper limit of

deviation deviation deviation
10% 270 330

No. of tablets No. of tablets Approval of batch

within limit without limit
20 QC of0
dosage forms Accepted 126
 Problem 2
• Solve the following
• The table below provides the weight of each of 20
ibuprofen tablets sampled during drug production for in-
process weight variation test (tablet specified weight is
200 mg). Guided by the USP, state whether this given
batch will be accepted or rejected.
• Justify your answer.

Tablet 1 2 3 4 5 6 7 8 9 10
Weight (mg) 187 204 255 200 200 190 210 215 190 204
Tablet 11 12 13 14 15 16 17 18 19 20
Weight (mg) 201 198 189 202 197 201 199 213 191 208
QC of dosage forms 127
 Solution
Tablet 1 2 3 4 5 6 7 8 9 10

• 204
Weight (mg) 187 204 255 200 200 190 210 215 190
Tablet 11 12 13 14 15 16 17 18 19 20
Weight (mg) 201 198 189 202 197 201 199 213 191 208
Average weight Percentage Lower limit Upper limit of
of deviation of deviation deviation
200 mg 7.5 % 185 215
Double limit of Double lower limit Double upper limit of
deviation of deviation deviation
15% 170 230

No. of tablets within No. of tablets without limit Approval of batch

limit
19 1(no.3 without double limit Rejected
of
QC deviation)
of dosage forms 128
 Problem 3
• Solve the following
The table below provides the weight of each of 20 tablets sampled
during drug production for in-process weight variation test
(tablet specified weight is 90 mg). Guided by the USP, state
whether this given batch will be accepted or rejected.
Justify your answer.

Tablet 1 2 3 4 5 6 7 8 9 10
Weight (mg) 93 105 83 92 89 93 89 94 97 87
Tablet 11 12 13 14 15 16 17 18 19 20
Weight (mg) 96 98 99 84 81 83 90 92 88 94

QC of dosage forms 129

 Solution
Tablet 1 2 3 4 5 6 7 8 9 10
Weight
93 105 83 92 89 93 89 94 97 87
(mg)
Tablet 11 12 13 14 15 16 17 18 19 20
Average
Weight weight Percentage of Lower limit of Upper limit of
96 98 99 84 81
deviation 83 90
deviation 92deviation
88 94
(mg)
90 mg 10 % 81 99

Double limit of Double lower limit of Double upper limit

deviation deviation of deviation
20% 72 108

No. of tablets within No. of tablets without Approval of batch

limit limit
19 1(no.2) Accepted
QC of dosage forms 130
 4. Tablet friability ( official in USP)
- To determine the ability of the tablets to withstand abrasion
during packaging, handling and shipping.
- Friability is a property related to the hardness of the tablet.
• Ten tablets are dusted, weighed then placed in the drum of
the friabilator which is allowed to rotate for 4 minutes or for
100 revolutions.
• During each revolution, the tablets fall from a distance of 6
inches to undergo repeated shocks.
• The tablets are then re-dusted and re-weighed (only the
intact ones) .
131
 Initial weight − Final weight after rotation 4 min .
% Friability =  100
Initial weight

❑ Friability (% loss) =It must be less than or equal to1% but

❑ Some chewable tablets and most effervescent tablets are highly
friable and require special unit packaging.
 Friability test

Initial weight − Final weight after rotation 4 min .

% Friability =  100
Initial weight

❑ Friability (% loss) =It must be less than or equal to1% but

❑ Some chewable tablets and most effervescent tablets are highly
friable and require special unit packaging.

QC of dosage forms 133

 The % loss in weight is calculated to indicate the friability.
According to USP, The weight loss should not be more than
0.8%

134 Roche
QC ofFriabilator
dosage forms
4- Disintegration test
❑ It is the time required for the tablet to break into particles, the
disintegration test is a measure only of the time required under
a given set of conditions for a group of tablets to disintegrate
into particles which will pass through 10 mesh screen.

Generally the disintegration time is as follow:

1. For uncoated tablets is 30 minutes.
2. For coated tablets is 1 hour.
3. For soluble tablets and effervescent tablets should disintegrate
within 3 minutes.
4. Enteric-coated tablet should not disintegrate in simulated
gastric fluid (2 hour), but should disintegrate in simulated
intestinal fluid in 2 hours.
5. Chewable tablets are not subjected to the disintegration test.
4- Disintegration test
- Consists of a rack holding 6 glass or plastic tubes each having a 10-
mesh screen at its bottom.
- The tubes are raised and lowered at a fixed rate ( 30 cycle/ min.) in
the fluid maintained at 37 ± 2°C (body temp) by a water bath.

- Six tablets are placed one in each tube along with a plastic disk
over each tablet (to prevent tablet floating and impart a slight pressure
on the tablet to force any soft mass through the screen).
 ⦿ Liquids used in disintegration
⦿ Water,

⦿ simulated gastric fluid (PH =

1.2 HCl),
⦿ or Simulated intestinal fluid
Disintegration test

QC of dosage forms 138

 5- Dissolution rate

• Dissolution is the process by which a solid enters a solution .

• The dissolution rate is defined as the amount of drug substance
that goes into solution per time under standardized conditions of
liquid / solid interface, temperature, and solvent composition .
• Dissolution is one of most important quality control tests and
consider as tool for predicating bioavailability , in some cases,
replacing clinical studies to determine bioequivalence.
• In fact, a direct relationship between in vitro dissolution rate of
many drugs and their bioavailability has been demonstrated and is
generally referred as in vitro- in vivo correlation, IVIVC.
 5- Dissolution rate
The batch will be accepted if not less than 70% of the
labeled drug content of each tablet from 6 tablets
tested have released (dissolved) within 45 minutes.

- If 1 or 2 tablets fail the test, 6 more tablets are

tested. At least 10 of the 12 tablets must meet the
requirements.

-The dissolution results are plotted as concentration

versus time.
6. Dissolution test

QC of dosage forms 141

6- Hardness
❑ Tablet hardness, or tablet crushing strength is the
force required to break a tablet. Hardness of 4-6 Kg
is considered satisfactory to the tablet.
To change Newton (force) to kilogram (mass), use the
following equation:
1 Newton = 1 kilogram X 9.8 meter second-2
N.B.
- Acceleration = 9.8 m s-2
- Force = mass X acceleration
Newton = kilogram X meter second-2
- e.g. 40 Newton = 40/9.8 = 4.08 K
- e.g. 6 K = 6 X 9.8 = 58.8 Newton
Tablet hardness devices:
1- Monsanto or stokes hardness tester:
2- Pfizer hardness tester:
3- Electrical instrument:
It is digital instrument in which the force is applied
electrically. It gives more reproducible results e.g.
“Erweka” and “Pharma test” hardness testers.
 7- Content uniformity
This test to ensure that every tablet contains the labeled amount of
the drug within the prescribed limits (generally ±15%).
B.P Method:
1. Take 20 tablets randomly, mill and assay the content
according to the procedures in pharmacopeia.
2. Calculate the concentration of drug in 20 tablets and in
each tablet by dividing over 20.
. % Recovery = (content x 100 )/labeled amount.
The B.P permit ± 10% , i.e. the amount of active ingredient must
be 90% - 110%.
The batch rejected if one tablet deviate from limits.
• USP method :

1. Take 10 tablets from random samples of 30 tablets

and assay. If only one tablet deviate from USP
limits ± 15 % (85%-115%)

2. select another 30 tablets and assay individually .

The batch are accepted, if Not less than 29 tablets

obey the limits.
147 QC of dosage forms
Factors affecting content uniformity:

1. Non uniform distribution of the drug in

powder mixture or granulation.
2. Segregation of the powder mixture or
granulation during manufacture
processes.
3. Weight variation of the tablets.
8- Thickness

Tablet thickness is determined with a

micrometer. The allowed limit of thickness
variation is ±5% of the size of the tablet.
Variation in tablet thickness leads to
counting and packaging problems.
Thickness of the tablet depends on the
density of granulation, the pressure
applied to the tablet and the speed of
tablet compression.