Tablet PDF

Tablet
Introduction
1. Why do we need to convert an active pharmaceutical ingredient into a suitable dosage form?
2. What is a tablet?
3. Advantages and disadvantages of tablet as a dosage form
4. Key Wards
Why do we need to convert an active pharmaceutical ingredient into a suitable dosage form?
Active pharmaceutical compounds (drugs) are used for the treatment of a disease or for prophylactic purpose.
An Active Pharmaceutical Ingredient (API) may exist in solid, liquid or semisolid form. The API and excipients
are suitably processed in pharmaceutical industry to convert them into dosage forms such as tablet, capsule,
suspension, solution.
What is a tablet?
It is a solid dosage form each containing a unit dose of one or more medicament/s. Tablets are solid, flat or
biconvex discs prepared by compressing a drug or a mixture of drugs with or without suitable excipients.
Advantages of tablet as a dosage form 1. Large scale manufacturing is feasible in comparison to other dosage forms. Therefore, economy can be
achieved
2. Accuracy of dose is maintained since tablet is a solid unit dosage form
3. Tailor made release profile can be achieved
4. Longer expiry period and minimum microbial spillage owing to lower moisture content
5. As tablet is not a sterile dosage form, stringent environmental conditions are not required in the tablet
department
6. Ease of packaging (blister or strip) and easy handling over liquid dosage form
7. Easy to transport in bulk
8. Organoleptic properties (taste, appearance and odor) are best improved by coating of tablet
9. Product identification is easy and markings done with the help of grooved punches and printing with
edible ink
10. Different types of tablets are available like buccal, floating, colon targeting, effervescent, dispersible,
soluble, and chewable, etc
11. In composition to parenterals dosage form, a doctor or a nurse is not required for administration i.e. self
administration is possible
12. In comparison to capsules, tablets are more tamperproof
Disadvantages of tablet as a dosage form 1. It is difficult to convert a high dose poorly compressible API into a tablet of suitable size for human use
2. Difficult to formulate a drug with poor wet ability, slow dissolution into a tablet
3. Slow onset of action as compared to parenterals, liquid orals and capsules
4. The amount of liquid drug (e.g. Vitamin E, Simethicone) that can be trapped into a tablet is very less
5. Difficult to swallow for kids, terminally ill and geriatric patients
6. Patients undergoing radiotherapy cannot swallow tablet
Key Wards
Reasons to go for dosage form
i) To control organoleptic properties
ii) Achieve desired therapeutic level of drug
Types of tablets
With advancement in technology and increase in awareness towards modification in standard tablet to achieve
better acceptability as well as bioavailability, newer and more efficient tablet dosage forms are being developed.
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VARIOUS TYPES OF TABLETS

- ORAL TABLETS FOR INGESTION
- TABLETS USED IN THE ORAL CAVITY
- TABLETS ADMINISTERED BY OTHER ROUTES
- TABLETS USED TO PREPARE SOLUTION
ORAL TABLETS FOR INGESTION
1 Standard compressed tablet
2 Multiple compressed tablets
I. Compression coated tablet
II. Layered tablet
III. Inlay tablet
3 Modified Release tablet
4 Delayed action tablet
5 Targeted tablet
I. Floating tablet
II. Colon targeting tablet
6 Chewable tablets
7 Dispersible tablets
These tablets are meant to be swallowed intact along with a sufficient quantity of potable water. Exception is
chewable tablet. Over 90% of the tablets manufactured today are ingested orally. This shows that this class of
formulation is the most popular world wide and the major attention of the researcher is towards this direction.
TABLETS USED IN THE ORAL CAVITY
1 Lozenges and troches
2 Sublingual tablets
3 Buccal tablets
4 Dental cones
5 Mouth dissolved tablet
The tablets under this group are aimed release API in oral cavity or to provide local action in this region. The
tablets under this category avoids first-pass metabolism, decomposition in gastric environment, nauseatic
sensations and gives rapid onset of action. The tablets formulated for this region are designed to fit in proper
region of oral cavity
TABLETS ADMINISTERED BY OTHER ROUTES
1 Vaginal tablet
2 Implants
These tablets are administered by other route except for the oral cavity and so the drugs are avoided from
passing through gastro intestinal tract. These tablets may be inserted into other body cavities or directly placed
below the skin to be absorbed into systemic circulation from the site of application
TABLETS USED TO PREPARE SOLUTION
1. Effervescent tablet
2. Hypodermic tablet
3. Soluble tablet
The tablets under this category are required to be dissolved first in water or other solvents before administration
or application. This solution may be for ingestion or parenteral application or for topical use depending upon
type of medicament used.
KEY
When two or more active pharmaceutical ingredients are needed to be administered simultaneously and they are
incompatible, the best option for the formulation pharmacist would be to formulate multilayered tablet.
When we need to release the medicament slowly for long time duration after administration of a single tablet we
go for modified release formulation.
When we need to release the API at a specific site in the elementary tract, targeted drug delivery is a preferred
option.
Dispersible tablets disintegrate either rapidly in water, to form a stabilized suspension, or disperse
instantaneously in the mouth to be swallowed without the aid of water
Sublingual tablet is designed to dissolve in small quantity of saliva and used when immediate action within few
minutes is desired.
Buccal tablet is most often used when replacement hormonal therapy is to be administered.
Implants are inserted into subcutaneous tissue by surgical procedures where they are very slowly absorbed over
a period of a month or a year
Tablets Formulation
Excipients and their functionalities
Diluents
Binders
Disintegrants
Antifrictional Agents
Miscellaneous Excipients
Excipients are chosen in tablet formulation to perform a variety of functions like
1. For providing essential manufacturing technology functions (binders, glidants, lubricants may be
added)
2. For enhancing patient acceptance (flavors, colourants may be added)
3. For providing aid in product identification (colourants may be added)
4. For Optimizing or modifying drug release (disintegrants, hydrophilic polymers, wetting agents,
biodegradable polymers may be added)
5. For enhancing stability (antioxidant, UV absorbers may be added)
EXCIPIENT
Diluents or Fillers
Binders or Granulating agents or Adhesives
Disintegrants
Lubricants
Antiadherents
Glidants
MISCELLANEOUS
Wetting agents
Dissolution retardants
Dissolution enhancers
Adsorbents
Buffers
Antioxidants
Chelating agents
Preservatives
Colours
Flavours
Sweeteners
Excipients and their functions

Diluents or Fillers
Diluents make the required bulk of the tablet when the drug dosage itself is inadequate to produce tablets of
adequate weight and size.
Binders or Granulating agents or Adhesives
Binders are added to tablet formulations to add cohesiveness to powders, thus providing the necessary bonding
to form granules, which under compaction form a cohesive mass or a compact, which is referred to as a tablet.
Disintegrants
A disintegrant is added to most tablet formulations to facilitate a breakup or disintegration of the tablet when
placed in an aqueous environment.
Lubricants
Lubricants are intended to reduce the friction during tablet formation in a die and also during ejection from die
cavity.
Antiadherents
Antiadherents are added to reduce sticking or adhesion of any of the tablet granulation or powder to the faces of
the punches or to the die wall.
Glidants
Glidants are intended to promote the flow of tablet granulation or powder mixture from hopper to the die cavity
by reducing friction between the particles.
Wetting agents
Wetting agents are added to tablet formulation to aid water uptake during disintegration and assist drug
dissolution.
Dissolution retardants
Dissolution retardants as the name suggest, retards the dissolution of active pharmaceutical ingredient(s).
Dissolution enhancers
Dissolution enhancers as the name suggest, enhance the dissolution rate of active pharmaceutical ingredien(s).
Adsorbents
Adsorbents are capable of retaining large quantities of liquids without becoming wet; this property of absorbent
allows many oils, fluid extracts and eutectic melts to be incorporated into tablets.
Buffers
Buffers are added to provide suitable micro environmental pH to get improved stability and / or bioavailability.
Antioxidants
Antioxidants are added to maintain product stability, they act by being preferentially oxidized and gradually
consumed over shelf life of the product.
Chelating agents
Chelating agents are added to protect against autoxidation; they act by forming complexes with the heavy metal
ions which are often required to initiate oxidative reactions.
Preservatives
Preservatives are added to tablet formulation in order to prevent the growth of micro organisms
Colors
Colors are added to tablet formulation for following purposes: to disguise off color drugs, product identification
and for production of more elegant product.
Flavors
Flavors are added to tablet formulation in order to make them palatable enough in case of chewable tablet by
improving the taste.
Sweeteners
Sweeteners are added to tablet formulation to improve the taste of chewable tablets
Tablet formulations are usually designed to satisfy following criteria-Patient acceptability; accuracy and
uniformity of drug content; manufacturability; optimal drug dissolution and stability.
Excipients are any component other than active pharmaceutical ingredient(s) intentionally added to the
formulation of a dosage form. Excipients play a crucial role in design of the delivery system, determining its
quality and performance. Various excipients used in tablet formulation are diluents, binders, disintegrants,
lubricants, antiadherents, glidants, wetting agents, dissolution retardants, dissolution enhancers, absorbents,
buffers, antioxidants, chelating agents, preservatives, colors, flavors, sweeteners
Diluents
1 Introduction
2 Classification of diluents
2.1 Organic diluents
2.2 Inorganic diluents
2.3 Co-processed diluents
2.4 Key Phrases
Introduction
In order to facilitate tablet handling during manufacture and to achieve targeted content uniformity, the tablet
size should be kept above 2-3 mm and weight of tablet above 50 mg. Many potent drugs have low dose (for e.g.
diazepam, clonidine hydrochloride) in such cases diluents provide the required bulk of the tablet
Diluent Must Meet Certain Basic Criteria
Diluent should not react with the drug substance
It should not have any effect on the functions of other excipients
It should not have any physiological or pharmacological activity of its own
It should have consistent physical and chemical characteristics
It should neither promote nor contribute to segregation of the granulation or powder blend to which
they are added
It should be able to be milled (size reduced) if necessary in order to match the particle size distribution
of the active pharmaceutical ingredient
It should neither support microbiological growth in the dosage form nor contribute to any
microbiological load
It should neither adversely affect the dissolution of the product nor interfere with the bioavailability of
active pharmaceutical ingredient; it should preferably be colorless or nearly so
Classification of Diluents
Tablet diluents or fillers can be divided into following categories:
i)Organic materials - Carbohydrate and modified carbohydrates.

ii) Inorganic materials Calcium phosphates and others.
iii) Co-processed Diluents.
Addition of Diluent
Diluents are often added to tablet formulations for secondary reasons like to provide better tablet properties
such as:
i) To provide improved cohesion
ii) To allow direct compression manufacturing
iii) To enhance flow
iv) To adjust weight of tablet as per die capacity
Binders are added in tablet formulation to have required flow property and compressibility of powders.
Wet Granulation, Dry Granulation/Slugging, Direct Compression are major granule manufacturing methods.
Direct Compression Binders are more efficient than conventional binders.
Pregelatinized Starch is used as multifunctional excipient: tablet binder (wet granulating agent as well as direct
compression binder), diluent, disintegrant and flow aid.
Polyethylene Glycol used as meltable binder.
Granules are formed in three stages: Nucleation, Transition and Ball Growth.
Compatibility of binder with API and other excipients, characteristics of binder, process variables, and
apparatus variables affects the quality of granules.
Granules have to be evaluated in order to measure its suitability for tableting.
Disintegrants
1 Introduction
2 Mechanism of tablet disintegrants
3 Methods of addition of disintegrants
4 Types of disintegrants
4.1 Starch
4.2 Pregelatinized starch
4.3 Modified starch
4.4 Cellulose and its derivatives
4.5 Microcrystalline cellulose (MCC)
4.6 Alginates
4.7 Ion-exchange resin
4.8 Miscellaneous
4.9 Superdisintegrants
5 Factors affecting disintegration
5.1 Effect of fillers
5.2 Effect of binder
5.3 Effect of lubricants
5.4 Effect of surfactants
Introduction
Bioavailability of a drug depends in absorption of the drug, which is affected by solubility of the drug in
gastrointestinal fluid and permeability of the drug across gastrointestinal membrane. Disintegrants, an important
excipient of the tablet formulation, are always added to tablet to induce breakup of tablet when it comes in
contact with aqueous fluid and this process of desegregation of constituent particles before the drug dissolution
occurs, is known as disintegration process and excipients which induce this process are known as disintegrants.
The objectives behind addition of disintegrants are to increase surface area of the tablet fragments and to
overcome cohesive forces that keep particles together in a tablet
Disintegrating Mechanism
The tablet breaks to primary particles by the mechanisms listed below:By capillary action
By swelling
Because of heat of wetting
Due to disintegrating particle/particle repulsive forces
Due to deformation
Due to release of gases
By enzymatic action
CAPILLARY ACTION
Disintegration by capillary action is always the first step. When we put the tablet into suitable aqueous medium,
the medium penetrates into the tablet and replaces the air adsorbed on the particles, which weakens the
intermolecular bond and breaks the tablet into fine particles. Water uptake by tablet depends upon
hydrophilicity of the drug /excipient and on tableting conditions.
SWELLING
Perhaps the most widely accepted general mechanism of action for tablet disintegration is swelling Tablets with
high porosity show poor disintegration due to lack of adequate swelling force.
Heat of wetting (air expansion)
Disintegrating particle/particle repulsive forces
Deformation
Release of gases
Enzymatic reaction
When disintegrants with exothermic properties gets wetted, localized stress is generated due to capillary air
expansion, which helps in disintegration of tablet.
Another mechanism of disintegration attempts to explain the swelling of tablet made with non swellable
disintegrants.
During tablet compression, disintegranted particles get deformed and these deformed particles get into their
normal structure when they come in contact with aqueous media or water.
Carbon dioxide released within tablets on wetting due to interaction between bicarbonate and carbonate with
citric acid or tartaric acid. The tablet disintegrates due to generation of pressure within the tablet.
Enzymes presents in the body act as disintegrants. These enzymes destroy the binding action of binder and
helps in disintegration.
DISINTEGRATING ENZYMES
ENZYME
Amylase
Protease
Cellulase
Invertase
BINDER
Starch
Gelatin
Cellulose and its derivatives
Sucrose
Disintegrants Addition
The method of addition of disintegrants is also a crucial part. Disintegrating agent can be added either prior to
granulation (intragranular) or prior to compression (after granulation i.e.extragranular) or at the both processing
steps. Extragranular fraction of disintegrant (usually, 50% of total disintegrant requires) facilitates breakup of
tablets to granules and the intragranular addition of disintegrants produces further erosion of the granules to fine
particles.
Types of disintegrants
Starch
Pregelatinized starch
Modified starch
Starch was the first disintegrating agent widely used in tablet manufacturing. Before 1906 potato starch and
corn starch were used as disintegrants in tablet formulation. The mechanism of action of starch is wicking and
restoration of deformed starch particles on contact with aqueous fluid. The concentration of starch used is also
very crucial part
B. Pregelatinized starch is produced by the hydrolyzing and rupturing of the starch grain. It is a directly
compressible disintegrants and its optimum concentration is 5-10%. The main mechanism of action of
Pregelatinized starch is through swelling.
C. Starch is modified by carboxy methylation followed by cross linking, which is available in market as cross
linked starch. EX-SODIUM STARCH GLYCOLATE
Mechanism of action of this modified starches are rapid and extensive swelling with minimum gelling. And its
optimum concentration is 4-6 %.
DISINTEGRANTS LIST
Other Disintegrants
A. Cellulose and its derivatives
B. Microcrystalline cellulose (MCC)
C. Alginates
D. Ion-exchange resin
E. Miscellaneous
* Sodium carboxy methylcellulose (NaCMC and CARMELLOSE sodium) has highly hydrophilic structure
and is soluble in water. But when it is modified by internally crosslinking we get modified crosslinked cellulose
i.e. Crosscarmellose sodium
* MCC exhibit very good disintegrating properties because MCC is insoluble and act by wicking action. The
moisture breaks the hydrogen bonding between adjacent bundles of MCC.
* Alginic acid and salts of alginic acid. Alginic acid is insoluble in water, slightly acidic in reaction. Hence, it
should be used in only acidic or neutral granulation
* Ion exchange resin (AmbreliteIPR-88) has highest water uptake capacity than other disintegrating agents
like starch and Sodium CMC.
* The miscellaneous category includes disintegrants like surfactants, gas producing disintegrants and hydrous
aluminium silicate. GAS PRODUCING DISINTEGRATING AGENTS IS used in soluble tablet, dispersible
tablet and effervescent tablet.
Super-disintegrants
As days passes, demand for faster disintegrating formulation is increased. So, pharmacist needs to formulate
disintegrants i.e. Superdisintegrants which are effective at low concentration and have greater disintegrating
efficiency and they are more effective intragranularly. One drawback that it is hygroscopic therefore not used
with moisture sensitive drugs. Superdisintegrants act by swelling and due to swelling pressure exerted in the
outer direction or radial direction, it causes tablet to burst or the accelerated absorption of water leading to an
enormous increase in the volume of granules to promote disintegration.
SUPERDISINTEGRANTS
Factors affecting disintegration
Fillers Effect
Binders Effect
Lubricants Effect
Sarfactants Effect
1. The fillers affect both rate and mechanism of disintegration of tablet. Insoluble diluents produce rapid
disintegration with adequate amount of disintegrants.
2. As binding capacity of the binder increases, disintegrating time of tablet increases and this counteract the
rapid disintegration. Even the concentration of the binder can also affect the disintegration time of tablet.
3. Lubricants are hydrophobic and they are usually used in smaller size than any other ingredient in the tablet
formulation
4. Surfactants are recommended to decrease the hydrophobicity of the drugs the more hydrophobic the tablet the
greater the disintegration time.
Key Wards
Disintegrants are added to tablet to induce breakup when it comes in contact with aqueous fluid.
Disintegration by capillary action or by swelling is the major mechanism for disintegrants.
Disintegrant can be added intragranular or extragranular or at both stages.
Superdisintegrants have greater efficiency at low concentration and hence, their demand is increasing day by
day.
Selection of diluent
Organic diluents
Carbohydrates
Sugar and Sugar alcohols
Lactose- -lactose monohydrate, spray dried lactose and anhydrous lactose are widely used as diluent
Characteristics of -Lactose monohydrate
Lactose monohydrate is not directly compressible and therefore it is suitable for use in wet granulation.
It has poor flow properties.
-lactose monohydrate is water soluble.
It produces a hard tablet and the tablet hardness increases on storage.
Disintegrant is usually needed in lactose containing tablets.
Drug release rate is usually not affected.
It is usually unreactive, except for discoloration when formulated with amines and alkaline materials (i.e.
browning or maillard reaction).
It contains approximately 5% moisture and hence is a potential source of instability especially with moisture
sensitive drugs.
It is inexpensive.
Characteristics of Lactose spray dried
It is directly compressible diluent.
It exhibits free flowing characteristics.
It needs high compression pressures in order to produce hard tablets.
Its compressibility is adversely affected if dried below 3% moisture.
It has high dilution potential.
It is more prone to darkening in the presence of excess moisture, amines and other compounds due to the
presence of a furaldehyde.
Usually, neutral or acid lubricant should be used when spray dried lactose is employed.
Expensive compared to anhydrous and hydrous lactose.
Characteristics of Lactose anhydrous
Lactose anhydrous is a directly compressible diluent.
It does not exhibit free flowing property.
It can pick up moisture at elevated humidity as a result of which changes in tablet dimensions may occur.
It does not undergo a maillard reaction to the extent shown by spray dried lactose, although this may occur in
some cases to a slight degree.
It is inexpensive.
Sucrose
Characteristics of Sucrose or sugar
It requires high machine pressures, especially in cases with over wetted granulations.
It is water soluble.
It possesses good binding properties.
It is slightly hygroscopic.
It is inexpensive.
It produces gritty mouth feel (i.e., it is not free from grittiness).
It is a calorie contributor and is cariogenic.
Mannitol
Characteristics of Mannitol
It exhibits poor flow properties.
It requires high lubricant content.
It is probably the most expensive sugar used as a tablet diluent and is water soluble.
It is widely used in chewable tablets because of its negative heat of solution, its slow solubility and its mild
cooling sensation in mouth.
It can be used in vitamin formulation, where moisture sensitivity may create a problem.
It is comparatively non hygroscopic.
It is free from grittiness.
It possesses low caloric value and is noncariogenic.
Sorbitol
Characteristics of Sorbitol
It is highly compressible diluent and is water soluble.
It is hygroscopic in nature.
It has good mouth feel and sweet cooling taste.
It is free from grittiness.
It possesses low caloric value and is noncariogenic.
Cellulose
Powdered cellulose
Characteristics of Powdered cellulose
Powdered cellulose may be used alone or together with other fillers such as lactose, calcium phosphates,
dextrans and others.
It possesses poor compressibility and exhibits poor flow properties.
It has poor binding properties and low dilution potential.
It is water insoluble.
It possesses some degree of inherent lubricity.
It is inexpensive.
Microcrystalline Cellulose
Characteristics of Microcrystalline cellulose
Hard tablets, at low compression pressures, are usually obtained when MCC is used as tablet diluent.
It undergoes plastic deformation on compression and hence it is more sensitive to lubricants.
It exhibits fair flowability.
It exhibits binding properties.
It also possesses disintegrant activity and thus promotes fast tablet disintegration.
It is water insoluble.
Inorganic diluents
Calcium phosphates- the calcium phosphates, here includes, the dihydrate and anhydrous form of dibasic
calcium phosphate and tribasic calcium phosphate. They are granular insoluble materials. They are widely used
both as wet granulation and direct compression diluents in tablet formulation. Bulk density of calcium
phosphates is higher than that of organic fillers. Dibasic calcium phosphate is available commercially under the
trade name (Manufactured byDi-Tab Emcompress An anhydrous form of dibasic calcium phosphate is
available commercially under the trade name A-Tab Fujicalin, a novel commercially available free flowing
spherically granulated dicalcium phosphate anhydrous (SGDCPA) for direct tableting was compared with
directly compressible dicalcium phosphate dihydrate (DCPD) and it was found that SGDCPA exhibited same
good flowability and better compactibility Whereas in contrast to DCPD, SGDCPA exhibited significant
uptake of moisture when exposed to relative humidity exceeding 70 %.
Characteristic of Calcium Phosphates
They are directly compressible and are characterized by brittle fracture on compression during tableting process.
Hard tablets are produced when calcium phosphates are used as diluents. They exhibit good flow properties.
They are non hygroscopic.
They are inexpensive.
They are abrasive in nature and hence can cause wear of tablet tooling. Sometimes their alkalinity is a major
source of drug instability.
Co-processed diluents
Co-processing means combining two or more
materials by an appropriate process
Now a days direct compression technique has been one of the well-accepted methods of
tablet manufacture. An extensive range of materials from various sources have been
developed and marketed as directly compressible diluents such as lactose, starch,
cellulose derivatives, inorganic substance, polyalcohols, and sugar-based materials.
LIST OF CO-PROCESSED EXCIPIENTS USED TO ACHIEVE BETTER TABLETING
PROPERTIES
Key WARDS
Diluents make the required bulk of the tablet when the drug dosage itself is inadequate to produce tablets of
adequate weight and size.
Diluents are often added to tablet formulations for secondary reasons like to provide better tableting properties.
Tablet diluents or fillers can be divided into following categories:
i) Organic materials
ii) Inorganic materials
iii) Co-processed diluents
Tablet diluents or fillers may also be classified on the basis of their solubility in water as soluble diluent and
insoluble diluent.
Microcrystalline cellulose (MCC) is perhaps the most widely used direct-compression tablet filler.
Co-processing means combining two or more materials by an appropriate process.
The composite particles or co-processed excipients are introduced to provide better tableting properties than a
single substance or the physical mixture
Binders
Binder is one of an important excipient to be added in tablet formulation. In simpler words, binders or adhesives
are the substances that promotes cohesiveness. It is utilized for converting powder into granules through a
process known as Granulation
Contents
1 Why to go for Granulation?
2 Granulation Processes
3 Types of Binders
3.1 Direct compression (DC) Binders
3.2 Mechanism of granule formation
3.3 Near Infrared (NIR) spectroscopy : A tool for granulation end point measurement
3.4 Factors to be considered in Granulation
3.4.1 Compatibility
3.4.2 Characteristics of drugs and other excipients
3.4.3 Spreading of Binder
3.4.4 Type and quantity of Binder
3.4.5 Temperature and Viscosity
3.4.6 Method of Addition of Binder
3.4.7 Mixing Time
3.4.8 Material of Construction of Granulator
3.4.9 Type of Granulator
3.4.10 Process Variables
3.4.11 Apparatus Variables
3.4.12 Impeller Movement
3.5 Evaluation tests for Binders/Granules
3.5.1 Particle Size and Particle Size Distribution
3.5.2 Surface Area
3.5.3 Density
3.5.4 % Compressibility
3.5.5 Flow Properties
3.5.6 Friability
3.5.7 Moisture Content
3.6 Key Phrases
Granulation
Flow property or Fluidity is required to produce tablets of a consistent weight and uniform strength.
Compressibility is required to form a stable, intact compact mass when pressure is applied. These two
objectives are obtained by adding binder to tablet formulation and then proceeding for granulation process.
Granules so formed should possess acceptable flow property and compressibility.
Granulation
Granulation process are
*To improve appearance,
* To improve mixing properties,
* To avoid dustiness,
* To densify material,
* To reduce segregation,
in general to either eliminate undesirable properties or to improve the physical and chemical properties of fine
powders.
Granulation Processes
Granulation technique includes wet granulation and dry granulation/slugging wherein binders are added in
solution/suspension form and in dry form respectively. In Direct Compression, binders possessing direct
compressibility characteristics are used.
Types of Binders
CLASSIFICATION OF BINDERS
COMMONLY USED BINDERS
CHARACTERISTICS OF COMMONLY USED BINDER
Direct compression (DC) Binders
The use of Direct Compression for tableting has increased
For Direct Compression, directly compressible binders are required which should exhibit adequate powder
compressibility and flowability.
Direct Compression binders should be selected on the basis of compression behavior, volume reduction under
applied pressure and flow behavior in order to have optimum binding performance To ease of manufacture,
product stability and high efficiency directly compressible binders are used
COMMONLY USED DC BINDERS
CHARACTERISTICS OF DC BINDERS
Flow Behavior --DI TAB > SMCC(50) > DC Lactose , UNI PURE(DW) > Avicel (PH 101) > UNI PURE(LD)
Compressibility --UNI PURE (LD) > SMCC (50), Avicel (PH 101) > UNI PURE (DW), DC Lactose > DI TAB
CRUSHING STRENGTH--UNI PURE (LD) > SMCC (50) > UNI PURE (DW) > AVICEL (PH 101) > DC
Lactose &gt DITAB
Formation Of Granule
Mechanism Mainly the granules are forms in three mechanisms:
Nucleation
Transition
Ball growth or enlargement of the granule
Nucleation: Here, the particles adhere due to liquid bridges which are the initiation step of Granulation. These
adhered particles play a role of nucleus for further enlargement of granules.
Transition: Enlargement of nucleus takes place by two possible mechanisms. Individual particle adhere to the
nucleus or two or more nuclei combine among themselves.
Ball growth or enlargement of the granule:
Ball growth occurs either by Coalescence or Breakage or Abrasion Transfer or Layering. In Coalescence a
larger granule is formed when two or more granules are united. In Breakage granules break and the fragments
of granule adhere to other granules. This forms a layer of material over intact granules. In Abrasion Transfer
granule material are abraded through attrition by the agitation of granule bed and abraded material adheres to
other granules resulting into enlarged granules. In layering particles adheres to the already formed granules
increasing their size.
Granulation
Factors to be ConsideredCompatibility
Characteristics of drugs and other excipients
Spreading of Binder
Type and quantity of Binder
Temperature and Viscosity
Method of Addition of Binder
Mixing Time
Material of Construction of Granulator
Type of Granulator
Process Variables
Apparatus Variables
Impeller Movement
Evaluation tests for Binders/Granules
Particle Size and Particle Size Distribution
Surface Area
Density
% Compressibility
18. Friability
19. Moisture Content
Compressibility, particle size, surface area, porosity, hydrophobicity, solubility in binder are important while
fixing a granulation process.
1. The drug that exhibits poor compressibility requires the use of a strong binder (liquid glucose, sucrose,
etc.)
2. Hydrophilic drug/excipients exhibiting absorption characteristics require higher volume of binder as
compared to hydrophobic drug/excipients.
3. Spreading of binder/granulation solution on the powder blend is of paramount importance in successful
granulation. HPMC is a superior binder for paracetamol as compared to PVP.
4. The uniformity of the particle size, hardness, disintegration and compressibility of the granulation
depends on type and quantity of binder added to formulation.
5. Hard granulations results due to stronger binder or a highly concentrated binder solution .
6. Fragile granulations results due to insufficient quantity of binder which segregates easily.
7. Larger quantities of granulating liquid produce a narrower particle size range and coarser and hard
granules .
The temperature and viscosity of binder is also important.
1. Fluid (less viscous) binder exhibit good spreading behavior.
2. The method of addition of binder is also important.
3. The mixing time also determines quality of granules.
4. The material of construction of granulator determines the volume of binder
5. Fluidized Bed Granulator produces porous granules as compared to High Shear Granulators.
Higher degree of densification of the granules results due to higher impeller.
1. The apparatus variables in High Shear Mixer have a larger effect on granule growth than in Fluidized
Bed Granulators.
2. The characteristics of granules produced are affected by formulation and process variables.
3. The particle size of granules affect the average tablet weight, tablet weight variation, disintegration
time, granule friability, granulation flowability and the drying rate kinetics of wet granulations .
4. Surface area of the drug effects upon dissolution rate.
5. Granule density, True Density, Bulk Density may influence compressibility, tablet porosity, flow
property, dissolution and other Properties.
6. Compressibility is the ability of powder to decrease in volume under pressure.
Antifrictional Agents
Contents
1 Lubricants
1.1 Classification of lubricants
1.1.1 Water Insoluble Lubricants
1.1.2 Water Soluble Lubricants
2 Antiadherents
3 Glidants
4 Key Phrases
Lubricants
Definition- Lubricants are the agents that act by reducing friction by interposing an intermediate layer between
the tablet constituents and the die wall during compression and ejection.Primarily lubricants are required to act
at the tooling or material interface, lubricants should be incorporated in the final mixing step, after granulation
is complete. When hydrophobic lubricants are added to a granulation, they form a coat around the individual
particles (granules), which may cause an increase in the disintegration time and a decrease in the drug
dissolution rate.
Minimum Lubrication Time
Surface area is important parameter for deciding lubricant efficiency. Lubricants with high surface area are
more sensitive to changes in mixing time than lubricant with low surface area. Therefore lubricant mixing time
should be kept minimum. Additional lubricant is often added to the tablet formulations that are to be
compressed with curved face punches. The amount of lubricant increases as the particle size of the granulation
decreases but its concentration should not exceed to 1% for producing maximum flow rate
Lubricants Classification
Lubricant are classified according to their water solubility
-water insoluble and
-water soluble.
Selection of lubricant is depends partly on
*mode of administration,
*type of tablet,
*desired disintegration and
*dissolution properties,
*physicochemical properties of granules or powder
*and cost.
Water Insoluble And Water Soluble Lubricants
Example INSOLUBLE LUBRICANTS
Example SOLUBLE LUBRICANTS
Antiadherents
Prevent sticking to punches and die walls
EX- Talc, magnesium stearate and corn starch
Talc
Corn-starch
Colloidal silica
DL-Leucine
Sodium lauryl sulfate
Stearates
Glidants
GLIDANTS are added to the formulation to improve the flow properties of the material which is to be fed into
the die cavity and aid in particle rearrangement within the die during the early stages of compression.
Starch is a popular glidant because it has additional value of disintegrant.
Talc is superior to starch
Talc has retardant effect on dissolutiondisintegration profile.
Similar to lubricants glidants act by interposing their particles between those of material and lower the overall
interparticulate friction of the system by virtue of their reduced adhesive tendencies.
Key Wards
Lubricants are added to reduce the friction during compression.
Antiadherents avoid sticking to die walls and picking by punches.
Glidants improve the flow property of material/granules.

Miscellaneous Excipients
Contents
A.Wetting Agents
B. Dissolution Retardants
C. Dissolution Enhancers
D. Adsorbents
E. Buffers
F. Antioxidants
G.Chelating Agents
H.Preservatives
I. Colourants
J.Flavours
K.Sweeteners
L.Key Phrases
Wetting Agents in tablet formulation aid water uptake and thereby enhancing disintegration and assisting in
drug dissolution. Incorporation of anionic surfactant like Sodium Lauryl Sulphate (SLS) is known to enhance
the dissolution
Wetting agents are mainly added when hydrophobic drug is to be formulated into tablet. SLS, Sodium
diisobutyl sulfosuccinate are used as wetting agent in tablet formulation. Dissolution Retardants are
incorporated into tablet formulation only when controlled release of drug is required. Waxy materials like
stearic acid and their esters can be used as dissolution retardants. Dissolution enhancer are the agents that alter
the molecular forces between ingredients to enhance the dissolution of solute in the solvent. Fructose, Povidone,
Surfactants are used as dissolution enhancer.
Adsorbents are the agents that can retain large quantities of liquids. Liquids like Vitamin E can be incorporated
into tablets by addition of adsorbents Ex-anhydrous calcium phosphate, starch, magnesium carbonate, bentonite,
kaolin, magnesium silicate, magnesium oxide and silicon dioxide. Silicon dioxide ,the liquid glidant and an
adsorbent to be adsorbed ,first mixed with the adsorbent prior to incorporation into the formulation.
Buffers are added to maintain a required pH since a change in pH may cause significant alteration in stability.
Ex-sodium bicarbonate, calcium carbonate, and sodium citrate Antioxidants are added in tablet formulation to
protect drug from undergoing oxidation. Ex-ascorbic acid and their esters , alpha-tocopherol , ethylene diamine
tetra acetic acid sodium metabisulfite , sodium bisulfite , Butylated Hydroxy Toluene (BHT) , Butylated
Hydroxy Anisole (BHA) , citric acid , and tartaric acid .
Chelating agents tend to form complexes with trace amount of heavy metal ions inactivating their catalytic
activity in the oxidation of medicaments Ex-Ethylenediamine tetracetic acid and its salts, Dihydroxy Ethyl
Glycine, Citric Acid and Tartaric Acid Preservatives may be a part of tablet formulation in order to prevent the
growth of microorganisms
Ex-Parabens like methyl, propyl, benzyl, butyl p-hydroxy benzoate
Colourants neither contribute to therapeutic activity nor do they improve product bioavailability or stability.
Facilitate identification of similar looking products avoid mix ups; to overcome colour change on aging,
disguising of off-colour drugs, for brand image in the market , aesthetic appearance of the product Ex- dyes and
lakes which are FD & C and D & C approved Lakes are usually employed as dry powders for colouring , they
do not require the FDA certification before use in drug products. care should be taken to prevent colour
migration during drying , formulation should be checked for resistance to colour changes on exposure to light.
SYNTHETIC COLOURANTS used in pharma
Flavours & Sweeteners
Flavors are commonly used to improve the taste of chewable tablets as well as mouth dissolved tablets.
Flavors are incorporated either as solids (spray dried flavors) or oils or aqueous (water soluble) flavors. Solids
that is dry flavors are easier to handle and generally more stable than oils. The maximum amount of oil that can
be added to granulation without affecting tableting characteristics is 0.5 to 0.75 %w/w. aqueous flavors are less
used because of its instability on aging.
Sweeteners are added primarily to chewable tablets.
Saccharin is 500 times sweeter than sucrose, disadvantages are that it has a bitter aftertaste and is carcinogenic.
cyclamate is carcinogenic Aspartame is about 180 times sweeter than sucrose. Key Ward -Only FD&C and
D&C approved colourants can be incorporated into tablet formulation. Flavours and Sweeteners are one of the
important ingredients of chewable and mouth dissolving tablet formulation.
Properties of API for tablets formulation
Contents
1 High Purity
2 High stability
3 Good compatibility with excipients
4 Optimum bulk powder properties
5 Optimum and Uniform particle size-particle size distribution
6 Spherical shape
7 Good flowability
8 Optimum moisture content
9 Good compressibility
10 Absence of static charge on surface
11 Good organoleptic properties
12 Miscellaneous points
13 Key Phrases
High Purity -API has to be in pure form otherwise impurities can catalyze series of chemical reactions, e.g. in
case of hydrocortisone impurity of cupric ion causes oxidation of ketone functional group. High stability- The
API should be stable against photolysis, oxidation, hydrolysis, etc. to keep the formulation a simple one.
Compatibility with excipients- There should not be any kind of interaction between excipient and API.
Bulk Powder Properties
Prevent segregation.
Have optimum size tablet particularly for low potency-low density API.
Have good flow.
Uniform particle sizedistribution
Spherical shape
Good flowability
Optimum moisture content
Good compressibility
Absence of static charge on surface
Good organoleptic properties
Miscellaneous
API should have uniform particle size and close particle size distribution to confirmUniformity of content,
Uniformity of weight,
Disintegration time,
Granule friability,
Drying rate kinetics of wet granulation,
Flowability,
Compressibility,
Stability,
Dissolution,
Bioavailability
Spherical shape & Good flowability
The shape of particles decides flowability. Spherical shaped particles exhibit good flow as compared to needle
shaped particles.
Flow is important for having uniformity of weight and uniformity of drug content Improving Flowability :
*Addition of glidants
*Addition of fines
*By wet granulation
*By densification with help of slugging
Moisture Content
Moisture Content in not only in API but also in Granules is of prime important.
i) Total lack of moisture results into brittle tablet.
ii) Moisture affects flow, which in turn affects uniformity of content.
iii) High amount of moisture gives stickiness, which will affect compaction.
iv) Picking/sticking may be observed.
Moisture content can be controlled by:
i) Use of anhydrous salts.
ii) Use of non-aqueous solvent.
iii) Optimum drying time.
iv) Addition of finely powdered adsorbent like magnesium oxide.
Compressibility
The API should exhibit good compressibility, It depends upon its intrinsic naturea. Elasticity
Intrinsic nature of particle can be changed byi) Wet massing
ii) Pre-compression
iii) Plastic tabulating matrix (micro crystalline cellulose)Elastic material is less suitable for direct compression.
b. Plasticity
The crushing strength is dependent on the time that tablet spends in a die. Changing the turret speed can
change dwell time. Plastic materials may exhibit viscoelastic deformaiton
c. Brittle fracture
A particle fractures into small particles on application of pressure in a die. Brittle fracture also promotes
tableting.
Surface Static Charge
Absence of Surface Static Charge is important becauseAffects uniformity of dose and weight variation
During mixing it may cause segregation and lead to non-uniformity of content if API and excipients are charged.
Charged API may adhere to feed frame and result into serious damage to tablet equipment.
Organoleptic Properties
Many API are unpalatable and unattractive in their natural form. In such cases, tablet formulation require
certain care. API has to be checked for colour and taste. Ex- Ranitidine Hydrochloride, Specification says
White to pale yellow; pale yellow is a confusing term,varies from men to man.Where it is darker yellow, a bad
smell evolve. Whereas the potency even after degradation shows optimum due to development of colour and
imparts in absotbance. Similarly, Albendazole has a bad smell but it is a tablet to chew; therefore, bad smell is
a big problem. In tablet formulation these type of things are to be considered, and try to avoid or remove these
problem.
Colour-API should be colourless

For coloured API, the following steps shall be considered:
i) Select appropriate excipient to avoid mottling.
ii) Incorporate API in smallest particle size.
iii) Incorporate colour in dry form along with binder and activate mixture by addition of water or other
activator.
iv) Coating can be applied to conceal non- inform colour (sugar coated multivitamin tablet).
Taste -Ideally API should have no taste
The following taste masking options can be tried:
i.) Use of prodrug to decrease API solubility in saliva or to reduce affinity for taste receptor e.g.
Chloramphenicol Palmitate.
ii) Sugar coating or film coating.
iii) Addition of sweeteners like mannitol in cause of fast dissolving tablet or chewable tablet.
iv) Use of drug-ion exchange adsorbent in formulation.
v) Drug -cyclodextrin complex may exhibit good taste profile and good compressibility as well.
Miscellaneous
1. API should not exhibit sublime characteristics
2. Liquid APIs are less suitable for tablet
formulation. One of the options is conversion of
liquid in pseudosolid
Key Wards
High Purity to avoid contamination and degradation.
High stability against photolysis, oxidation, hydrolysis, etc.
Good compatibility with excipients. For example, avoid use of lactose with drugs with primary amine
functional group.
Optimum bulk powder properties to prevent segregation and to have good flow.
Optimum particle size and size distribution to have uniformity of weight, uniformity of content, good flow and
compressibility.
Spherical shape to avoid interlocking between the particles and thus to aid flow.
Good flow to have uniformity of weight and uniformity of drug content.
Optimum amount of moisture to avoid problems like brittle tablet, picking/sticking, etc.
Good compressibility to have nicely bonded tablet.
Absence of static charge on the surface to prevent demixing and damage to tableting equipment by adhering to
feed frame.
Good organoleptic properties to have better patient acceptance.
Miscellaneous: Convert liquid API to pseudosolid e.g. Valproic acid and Sodium valproate, etc.
Tablet Manufacturing Operations
Contents
1 Introduction
2 Dispensing
3 Sizing
4 Powder blending
5 Granulation
6 Drying
7 Tablet compression
8 Auxiliary Equipments
8.1 Granulation Feeding Device
8.2 Tablet weight monitoring devices
8.3 Tablet Deduster
8.4 Fette machine
9. Packaging
9.1 Key Phrases
Introduction
The manufacture of tablets is a complex multi- stage process in which the starting materials change their
Physical characteristics a number of times before the final dosage form is produced. Tablets can be made by
granulation, a process that imparts two primary requisites to formulate:
compactibility and fluidity.
In making tablet Both wet granulation and dry granulation (slugging and roll compaction) are used.
Other unit operation involves are-particle size reduction and sizing, blending, granulation, drying, compaction,
and (frequently) coating.
Typical Manufacturing Operation
Dispensing
Dispensing is the first step in any pharmaceutical manufacturing process.
Dispensing is one of the most critical steps .
Dispensing may be done by purely manual or automated dispensaries with mechanical devices
Weighing accuracy, Dust control (laminar air flow booths, glove boxes), during manual handling, Lot control of
each ingredient, Material movement into and out of dispensary should be considered during dispensing.
Sizing
Size Reduction, Milling, Crushing, Grinding, Pulverization) Is An Impotent Step (Unit Operation) Involved In
The Tablet Manufacturing
In manufacturing of compressed tablet, the mixing or blending is easier and more uniform if the ingredients are
approximately of same size.
A fine particle size is essential in case of lubricant mixing which provides a greater uniformity of dose.
Advantages of size reduction
It increases surface area, enhance dissolution rate and hence bioavailability.
Improved the tablet-to-tablet content uniformity .
Promote better flow of mixture in tablet machine.
Improved flow properties of raw materials.
Improved colour and/or active ingredient.
promote uniform drying.
Disadvantages
A possible change in polymorphic form of the active ingredient, rendering it less or totally inactive, or unstable.
Decrease in bulk density cause flow problem and segregation in the mix.
Promote the adsorption of air,by increase in surface area from size reduction cause longer dissolution rate.
Dry sizing or milling Machine- Fluid energy mill, Colloidal mill, Ball mill, Hammer mill, Cutting mill,
Roller mill, Conical mill. HUABlending
The powder/granules blending are involved at stage of pre granulation and/or post granulation stage of tablet
manufacturing.
Each process of mixing has optimum mixing time, mixing speed.
A simple tumble blender may use, V blender, Oblicone blender, Container blender,
Tumbling blender, Agitated powder blender are some example.
Granulation
Following particle size reduction and blending, the formulation may be granulated, which provides
homogeneity of drug distribution in blend.
Drying
Drying is a most important step in the formulation and development of pharmaceutical product. It is important
to keep the residual moisture low enough to prevent product deterioration and ensure free flowing properties.
The commonly used dryer includes
Fluidized bed dryer, Vacuum tray dryer, Microwave dryer, Spray dryer, Freeze dryer,
Turbo - tray dryer, Pan dryer, etc.
Tablet compression
After the preparation of granules ( wet granulation) or
Sized slugs (dry granulation) or
Mixing of ingredients (direct compression)- granules are compressed to get final product.
Tablet may be of different shapes,sizes although they are usually round or oval.
Each tablet is made by pressing the granules inside a die by two punches (UPPER-LOWER)
Turret & Cams
The punches and dies are fixed to a turret that spins round. As it spins, the punches are driven together by two
fixed cams - an upper cam and lower cam. The top of the upper punch (the punch head) sits on the upper cam
edge .The bottom of the lower punch sits on the lower cam edge.
The shapes of the two cams determine the equence of movements of the two punches.
This sequence is repeated over and over because the turret is spinning round.
Other Necessary Equipment
Granulation Feeding Device
Mechanized/Force feeder
Tablet weight monitoring devices
Tablet Deduster
Metal Detector
Chilling Device for thermolebile product
Blister Packing
Strip Packing
Bottle Packing
Key wards
Particle size reduction and sizing
Blending
Granulation
Drying, compaction
Coating.
Tablet
The Methods of Manufacture
Two main methods are practiced world wide in manufacturing of Pharmaceutical Tablets
Direct Compression
Wet Granulation
Direct compression
Contents
1 Introduction
2 The events that motivates the industry people to use direct compression technique
3 Merits
4 Merits over wet granulation process

5 Demerits
6 Manufacturing steps for direct compression
7 Direct compression Excipients
7.1 An ideal direct compression excipient should possess the following attributes
7.2 Major excipients required in direct compression
7.2.1 Diluents
7.2.2 Binders
7.2.3 Disintegrants
8 Key Wards
Introduction
Definition:
The term direct compression is defined as the process by which tablets are compressed
directly from powder mixture of Active Pharmaceutical Ingredients (API) and suitable excipients.
No pretreatment of the powder blend by wet or dry granulation procedure is required.
The Events Of Motivation For Direct Compression
I.Commercial availability of the directly compressible excipients possessing both good compressibility and
good flowability.
II. Major advances in tablet compression machinery,
i) Improved positive die feeding
ii) Precompression of powder blend
Merits Of DIRECT COMPRESSION
Direct compression is more efficient ,involves only dry blending and compaction of API and necessary
excipients.
Important advantage of direct compression is economical process.Reduced processing time, reduced labor costs,
fewer manufacturing steps, and less number of equipments are required, less process validation, reduced
consumption of power.
Elimination of heat and moisture, thus increasing not only the stability but also the suitability of the process for
thermolabile and moisture sensitive APIs.
Particle size uniformity.
Prime particle dissolution.
The chances of batch-to-batch variation are negligible, because the unit operations required for manufacturing
processes is fewer.
Chemical stability problems for API and excipient would be avoided.
Provides stability against the effect of aging which affects the dissolution rates.
Demerits of Direct Compression
Excipient Related
Process Related
Problems in the uniform distribution of low dose drugs.
High dose drugs having high bulk volume, poor compressibility and poor flowability are not suitable for direct
compression. The choice of excipients for direct compression is extremely critical. Direct compression diluents
and binders must possess both good compressibility and good flowability. Many active ingredients are not
compressible either in crystalline or amorphous forms. Direct compression blends may lead to unblending
because of difference in particle size or density of drug and excipients. Similarly the lack of moisture may give
rise to static charges, which may lead to unblending. Non-uniform distribution of colour, especially in tablets of
deep colours. Capping, lamination, splitting, or layering of tablets is sometimes related to air entrapment during
direct compression. When air is trapped, the resulting tablets expand when the pressure of tablet is released,
resulting in splits or layers in the tablet. In some cases require greater sophistication in blending and
compression equipments.
Direct compression equipments are expensive.
Three Steps Operation

Milling of drug and excipients.
Mixing of drug and excipients.
Tablet compression.
Excipients For Direct compression- Direct compression excipients mainly include diluents, binders and
disintegrants. The success of direct compression formulation is highly dependent on functional behavior of
excipients.
Expected Characters for Direct Compressible Excipients*It should have good compressibility.
*It should possess good hardness after compression, that is material should not
possess any deformational properties; otherwise this may lead to capping and lamination of tablets.
*It should have good flowability.
*It should be physiologically inert.
*It should be compatible with wide range of API.
*It should be stable to various environmental conditions (air, moisture, heat, etc.).
*It should not show any physical or chemical change in its properties on aging. Cont-*It should have high dilution potential. i.e. Able to incorporate high amount of API.
*It should be colourless, odorless and tasteless.
*It should accept colourants uniformity.
*It should possess suitable organoleptic properties according to formulation type, that
is in case of chewable tablet diluent should have suitable taste and flavor. For example
mannitol produces cooling sensation in mouth and also sweet test.
*It should not interfere with bioavailability and biological activity of active ingredients.
*It should be easily available and economical in cost.
Diluents-Selection of direct compression diluent is extremely critical, because the success or failure of direct
compression formulation completely depends on characteristics of diluents. Properties of API (particle size and
shape, bulk density, solubility), flowability, compressibity . stability (moisture, light, and other environmental
factors),
Binders- Binders are the agents used to impart cohesive qualities to the powdered material. direct compressible
materials are not only free flowingbut also sufficiently cohesive to act as binder.
Disintegrants- Disintegrants are the agents
Key Wards- advanced technologies to prepare tablets , requires only blending and compression of excipients,
economical process , suitable for heat and moisture sensitive API and not suitable for very low and very high
dose drugs.
Wet granulation
1 Introduction
2 Wet granulation
2.1 Introduction
2.2 Important steps involved in the wet granulation
2.3 Limitation of wet granulation
2.4 Special wet granulation techniques
2.4.1 High shear mixture granulation
2.4.2 Fluid bed granulation
2.4.3 Extrusion and Spheronization
2.4.4 Spray drying granulation
2.5 Lists of equipments for wet granulation
2.6 Current topics related to wet granulation
3 Dry granulation
3.1 Introduction
3.2 Advantages
3.3 Disadvantages
3.4 Steps in dry granulation
3.5 Two main dry granulation processes
3.5.1 Slugging process
3.5.2 Roller compaction
3.6 Formulation for dry granulation
4 Advancement in Granulations
4.1 Steam Granulation
4.2 Melt Granulation / Thermoplastic Granulation
4.3 Moisture Activated Dry Granulation (MADG)
4.4 Moist Granulation Technique (MGT)
4.5 Thermal Adhesion Granulation Process (TAGP)
4.6 Foam Granulation
5 Key Phrases
Introduction
Definition - Granulation may be defined as a size enlargement process which converts small particles into ically
stronger & larger agglomerates.
Characteristics of granules- The ideal characteristics of granules include spherical shape, smaller particle size
distribution with sufficient fines to fill void spaces between granules, adequate moisture (between 1-2%), good
flow, good compressibility and sufficient hardness.
Properties of granulation
Particle size of the drug and excipients
Type of binder (strong or weak)
Volume of binder (less or more)
Wet massing time ( less or more)
Amount of shear applied
Drying rate ( Hydrate formation and polymorphism)
Steps involved in the wet granulation
Wet granulation process simply involves wet massing of the powder blend with granulating liquid, wet sizing
and drying.
i) Mixing of the drug(s) and excipients
ii) Preparation of binder solution
iii) Mixing of binder solution with powder mixture to form wet mass.
iv) Coarse screening of wet mass using a suitable sieve (6-12 #screens).
v) Drying of moist granules.
vi) Screening of dry granules through a suitable sieve (14-20 #screen).
vii) Mixing of screened granules with disintegrant, glidant, and lubricant.
Wet Granulation-Limiting Factors
The greatest disadvantage of wet granulation is its cost. It is an expensive process because of labor, time,
equipment, energy and space requirements.
Loss of material during various stages of processing
Stability may be major concern for moisture sensitive or thermo labile drugs
Multiple processing steps add complexity and make validation and control difficult
An inherent limitation of wet granulation is that any incompatibility between formulation components is
aggravated.
Wet Granulation Techniques
*High shear mixture granulation
High shear mixture has been widely used in Pharmaceutical industries for blending and granulation. Blending
and wet massing is accompanied by high mechanical agitation by an impeller and a chopper.
AdvantagesShort processing time

Less amount of liquid binders required compared with fluid bed.
Highly cohesive material can be granulated.
*Fluid bed granulation
Fluid bed granulation is a process by which granules are produced in a single equipment by spraying a binder
solution onto a fluidized powder bed. The material processed by fluid bed granulation are finer, free flowing
and homogeneous.
*Extrusion-spheronization
It is a multiple step process capable of making uniform sized spherical particles=
AdvantagesAbility to incorporate higher levels of active components without producing excessively larger particles.
Applicable to both immediate and controlled release dosage form.
*Spray drying
It is a unique granulation technique that directly converts liquids into dry powder in a single step. This
method removes moisture instantly and converts pumpable liquids into a dry powder.
AdvantagesRapid process
Ability to be operated continuously
Suitable for heat sensitive product
Special wet granulation techniques
High shear mixture granulation
High shear mixture has been widely used in Pharmaceutical industries for blending and ranulation. Blending
and wet massing is accompanied by high mechanical agitation by an impeller and a chopper.
Advantages:
1. Short processing time
Less amount of liquid binders required compared with fluid bed.
Highly cohesive material can be granulated.
ii) Fluid bed granulation
Fluidization is the operation by which fine solids are transformed into a fluid like state.
Fluid bed granulation is a process by which granules are produced in a single equipment by spraying a binder
solution onto a fluidized powder bed.
iii) Extrusion-spheronization
It is a multiple step process capable of making uniform sized spherical particles. It is primarily used as a
method to roduce multi-particulates for controlled release application.
Advantages:
Ability to incorporate higher levels of active components without producing excessively larger particles.
Applicable to both immediate and controlled release dosage form.
iv) Spray drying
It is a unique granulation technique that directly converts liquids into dry powder in a single step. This
method removes moisture instantly and converts pumpable liquids into a dry powder.
Advantages:
Rapid process
Ability to be operated continuously
8. Suitable for heat sensitive product
Lists of equipments for wet granulation
High Shear granulation:
Little ford Lodgie granulator
Little ford MGT granulator
Diosna granulator
Gral mixer
Granulator with drying facility:
Fluidized bed granulator

Day nauta mixer processor
Double cone or twin shell processor
Topo granulator
Special granulator:
Roto granulator
Marumerizer
Dry granulation
Introduction - In dry granulation process the powder mixture is compressed without the use of heat and solvent.
It is the least desirable of all methods of granulation. The two basic procedures are to form a compact of
material by compression and then to mill the compact to obtain a granules.
Advantages
The main advantages of dry granulation or slugging are that it uses less equipments and space.
For moisture sensitive material
For heat sensitive material
For improved disintegration since powder particles are not bonded together by a binder
Disadvantages
It requires a specialized heavy duty tablet press to form slug
It does not permit uniform colour distribution as can be achieved with wet granulation where the dye can be
incorporated into binder liquid.
3. The process tends to create more dust than wet granulation, increasing the potential contamination.
Steps in dry granulation
i) Milling of drugs and excipients
ii) Mixing of milled powders
iii) Compression into large, hard tablets to make slug
iv) Screening of slugs
v) Mixing with lubricant and disintegrating agent
vi) Tablet compression
Factors which determine how well a material may slug
i) Compressibility or cohesiveness of the mater
ii) Compression ratio of powder
iii) Density of the powder
iv) Machine type
v) Punch and die size
vi) Slug thickness
vii) Speed of compression
viii) Pressure used to produce slug
Advancement in Granulations
Steam Granulation
Melt Granulation / Thermoplastic Granulation
Moisture Activated Dry Granulation (MADG)
Moist Granulation Technique (MGT)
Thermal Adhesion Granulation Process (TAGP)
Foam Granulation
Steam Granulation
It is modification of wet granulation. Here steam is used as a binder instead of water.
Benefits includes :
Higher distribution uniformity,
Higher diffusion rate into powders,
More favourable thermal balance during drying step,
Steam granules are more spherical,

Have large surface area hence increased dissolution rate of the drug from granules,
Processing time is shorter therefore more number of tablets are produced per batch,
Compared to the use of organic solvent water vapour is environmentally friendly,
No health hazards to operators,
No restriction by ICH on traces left in the granules,
Freshly distilled steam is sterile and therefore the total count can be kept under control,
Lowers dissolution rate so can be used for preparation of taste masked granules without modifying availability
of the drug.
Key Wards
In wet granulation process a granulating liquid is used to facilitate the agglomeration process. Wet granulation
has been and continues to be the most widely used agglomeration process. Typically wet massing of
pharmaceutical powder is carried out in the high shear mixture before wet screening and dried in fluidized bed
equipment.
In the dry granulation process granulation takes place without utilizing liquid. In this process dry powder
particles may be brought together mechanically by compression into slug or by rolled compaction.
Steam Granulation, Melt Granulation, MADG, MGT, TAGP, Foam Granulation are some of the new
advancements in granulation and show better quality granule formation as compared to conventional
granulation methods.
Introduction
Coated tablets are defined as tablets covered with one or more layers of mixture of various substances such as
natural or synthetic resins ,gums ,inactive and insoluble filler, sugar, plasticizer, polyhydric
alcohol ,waxes ,authorized colouring material and some times flavoring material .
Aspects of tablet coating
1. Therapy
i) Avoid irritation of oesophagus and stomach
ii) Avoid bad taste
iii) Avoid inactivation of drug in the stomach
iv) Improve drug effectiveness
v) Prolong dosing interval
vi) Improve dosing interval
vii) Improve patient compliance
2. Technology
i) Reduce influence of moisture
ii) Avoid dust formation
iii) Reduce influence of atmosphere
iv) Improve drug stability
v) Prolong shelve life
3. Marketing
i) Avoid bad taste
ii) Improve product identity
iii) Improve appearance and acceptability
The Basic principle
Tablet coating is the application of coating composition to moving bed of tablets with concurrent use of heated
air to facilitate evaporation of solvent.
INVOLVE
i) Insulation which influences the release pattern as little as possible and does not markedly change the
appearance.
ii) Modified release with specific requirement and release mechanism adapted to body function in the digestive
tract.
iii) Colour coating which provides insulation or is combined with modified release coating.
Coating Process
Type of coating
Sugar coating
Sugar coating provides a combination of insulation, taste masking, smoothing the tablet core, colouring and
modified release.
Film Coating------Film coating is more favored over sugar coating and widely used
Sugar Coating Five Separate Operations
1. Sealing/Water proofing: provides a moisture barrier and harden the tablet surface.
2. Subcoating: causes a rapid buildup to round off the tablet edges.
3. Grossing/Smoothing: smoothes out the subcoated surface and increases the tablet size to predetermine
dimension.
4. Colouring: gives the tablet its colour and finished size.
5. Polishing: produces the characteristics gloss.
Sealcoating
Sealcoating is also known as water proofing
The tablet cores must be sealed, thoroughly dried and free of all residual solvents, prior to applying any sugarsyrup.
The seal coat provides a moisture barrier and hardness the surface of the tablet
The sealants are generally water-insoluble polymers
Common sealant include :Shellac, Zine, Cellulose acetate phthalate (CAP), Polyvinylacetate phthalate,
Hyroxylpropylcellulose, Hyroxypropylmethylcellulose
Subcoating
Generally two methods are used for subcoating:
i)The application of gum based solution followed by dusting with powder and then drying. This routine is
repeated until the desired shape is achieved.
ii)The application of a suspension of dry powder in gum/sucrose solution followed by drying
TYPICAL SUBCOATING SOLUTION
DUSTING POWDER FOR SUBCOATING
FORMULATION FOR SUBCOATING SUSPENSION
Smoothing
To increases the tablet size to a predetermined dimension.
The smoothing process is specifically for smoothing and filing the irregularity on the surface generated during
subcoating.
Smoothing usually can be accomplished by the application of a simple syrup solution (approximately 60-70 %
sugar solid).
Colour
The successful completion of a sugar coating process is often most critical.
coating
The process and involves the multiple application of syrup solution (60-70 % sugar solid) containing colouring
matter.
Soluble dyes are used in the sugar coating to achieve the desired colour.
Polishing
Sugar-coated tablets needs to be polished to achieve a final elegance. Polishing is achieved by applying the
mixture of waxes like beeswax, carnubawax, candelila wax or hard paraffin wax to tablets in polishing pan.
Film
Coating
Film coating Process description
Definition-Film coating is deposition of a thin film of polymer surrounding the tablet core.
Traditionally Conventional pan equipments is used, but now a days more sophisticated equipments are
employed to have a high degree of automation and coating time.
The drying conditions cause removal of the solvent.
The Process
Usually spray process is employed in preparation of film coated tablets. Accela cota is the prototype of
perforated cylindrical drum providing high drying air capacity. Fluidized bed equipment has made considerable
impact where tablets are moving in a stream of air passing through the perforated bottom of a cylindrical
column. With a smaller cylindrical insert, the stream of cores is rising in the center of the device together with a
spray mist applied in the middle of the bottom.
Process Requirements
Adequate means of atomizing the spray liquid for application to the tablet core.
Adequate mixing and agitation of tablet bed.
Sufficient heat input in the form of drying air to provide the latent heat of evaporation of the solvent.
Good exhaust facilities to remove dust and solvent is necessary.
Formulations Development
Why to go for film Coating?
Is it necessary to mask objectionable taste, colour and odor?
Is it necessary to control drug release?
What tablets size, shape, or colour constrains must be placed on the developmental work?
Colour, shape and size of final coated tablet are important for marketing.
Film Coating Materials
Film formers, which may be enteric or nonenteric
Solvents
Plasticizers
Colourants
Opaquant-Extenders
Miscellaneous coating solution components
1. Film formers
Film coating materials should have the following characteristicsi) Solubility in solvent of choice for coating preparation
ii) Solubility requirement for the intended use e.g. free water-solubility, slow water-solubility or pH -dependent
solubility
iii) Capacity to produce an elegant looking product
iv) High stability against heat, light, moisture, air and the substrate being coated
v) No inherent colour, taste or odor
vi) High compatibility with other coating solution additives
vii) Nontoxic with no pharmacological activity
viii) High resistance to cracking

ix) Film former should not give bridging or filling of the debossed tablet
x) Compatible to printing procedure
Film Formers
Hydroxy Propyl Methyl Cellulose (HPMC)
Methyl Hydroxy Ethyl Cellulose (MHEC)
Ethyl Cellulose (EC)
Hydroxy Propyl Cellulose (HPC)
Povidone
Sodium carboxy methyl cellulose
Polyethylene glycols (PEG)
Acrylate polymers -----and so on
HPMC-It is available in different viscosity grades. It has solubility characteristic in gastric fluid, organic and
aqueous solvent system
Advantages -it does not affect tablet disintegration and drug availability, it is cheap, flexible, highly resistant to
heat, light and moisture, it has no taste and odor, colour and other additives can be easily incorporated.
Disadvantage -when used alone, the polymer has tendency to bridge or fill the debossed tablet surfaces. So
mixture of HPMC and other polymers/ plasticizers is used.
Methyl Hydroxy Ethyl Cellulose -It is available in wide variety of viscosity grades. It is not frequently used as
HPMC because soluble in fewer organic solvents.
Ethyl Cellulose -Different viscosity grades are available, insoluble in water and gastric fluids , it is used in
combination with water-soluble additives like HPMC and not alone.
Povidone -It is available in four viscosity grades i.e. K-15, K-30, K-60 and K-90. Average molecular weight of
these grades is 10000, 40000, 160000 and 360000 respectively. K-30 is widely used as tablet binder and in
tablet coating.
Sodium carboxy methyl cellulose -It is available in medium, high and extra high viscosity grades. It is easily
dispersed in water to form colloidal solutions but it is insoluble in most organic solvents and hence not a
material of choice for coating solution based on organic solvents.
Polyethylene glycols (PEG)-Lower molecular weights PEG (200-600) are liquid at room temperature and are
used as plasticizers. High molecular weights PEG (900-8000series) are white, waxy solids at room temperature.
Combination of PEG waxes with CAP gives films that are soluble in gastric fluids.
Acrylate polymers -EudragitIt is marketed under the name of Eudragit E is freely soluble in gastric fluid up to
pH 5 andco-polymer . It is available as organic solution (12.5% in isopropanol/acetone), solid material or 30%
aqueous RLdispersion. They produce films for delayed action.
Solvents
Solvents are used to dissolve or disperse the polymers
i) Should be either dissolve/disperse polymer system
ii) Should easily disperse other additives into solvent system
iii) Small concentration of polymers (2-10%) should not in an extremely viscous solution system creating
processing problems
iv) Should be colourless, tasteless, odorless, inexpensive, inert, nontoxic and nonflammable
v) Rapid drying rate
vi) No environmental pollution.
Plasticizers
Internal or External plasticizing technique is used to modify quality of film.
Combination of plasticizer may be used to get desired effect. Concentration of plasticizer is expressed in
relation to the polymer being plasticized. Recommended levels of plasticizers range from 1-50 % by weight of
the film former.
EX-castor oil, PG, glycerin, lower molecular weight (200-400 series), PEG, surfactants, etc.
Colourants
Most common colourants in use are certified FD & C or D & C colourants. These are synthetic dyes or lakes.
Lakes are choice for sugar or film coating as they give reproducible results.
The inorganic materials (e.g. iron oxide) and the natural colouring materials (e.g. anthrocyanins, carotenoids,
etc) are also used to prepare coating solution.
Homogenous distribution of suspended colourants in the coating solution requires the use of the powdered
colourants (<10 microns).
Opaquant-Extenders
Opaquant are very fine inorganic powder used to provide more pastel colours and increase film coverage.
Colourants are expensive and need higher concentration.
Ex- titanium dioxide, silicate (talc &aluminum silicates), carbonates (magnesium carbonates), oxides
(magnesium oxide) & hydroxides (aluminum hydroxides).
Miscellaneous
Flavors, sweeteners, surfactants, antioxidants, antimicrobials, etc. may be incorporated into the coating solution.
Enteric coating
This type of coating is used to protect tablet core from disintegration in the acid environment of the stomach for
one or more of the following reasonsTo prevent degradation of acid sensitive API
To prevent irritation of stomach by certain drugs like sodium salicylate
Delivery of API into intestine
To provide a delayed release component for repeat action tablet Several kinds of enteric layer systems are now
availableOne layer system
Two layer system
Properties of enteric coating material
Susceptible/permeable to intestinal fluid
Resistance to gastric fluids
Compatibility with most coating solution components and the drug substrate
Formation of continuous film
Nontoxic, cheap and ease of application
Ability to be readily printed
Polymers for enteric coating
Cellulose acetate phthalate (CAP) composed of solid or semisolid polymer spheres of CAP ranging in size from
0.05 3 microns CAP films are brittle and usually used with other hydrophobic film Acrylate polymers
EudragitL & EudragitS are two forms of commercially available enteric acrylic resins. Both of them
produce films resistant to gastric fluid.
Hydroxy propyl methyl cellulose phthalate (HPMCP)
HPMCP 50, 55 & 55-s (also called HP-50, HP-55 & HP-55-s) is widely used. HP-55 is recommended for
general enteric preparation while HP-50 & HP-55-s for special cases.
These polymers dissolve at a pH 5-5.5.
Polyvinyl acetate phthalate stable and pH dependent solubility
Enteric sugar coating
Here the sealing coat is tailored to include one of the enteric polymers in sufficient quantity to pass the enteric
test for disintegration. The sub coating and subsequent coating steps are then as for conventional sugar coating.
Enteric film coating
Enteric polymers are capable of forming a direct film in a film coating process. Sufficient weight of enteric
polymer has to be used to ensure an efficient enteric effect.
Controlled release coating
Polymers like modified acrylates, water insoluble cellulose (ethyl cellulose), etc. used for control release
coating.
Specialized coating
Compressed coating the tablet core cannot tolerate organic solvent or water and yet needs to be coated for taste
masking or to provide delayed or enteric properties
Electrostatic coating
A strong electrostatic charge is applied to the substrate. The coating material containing conductive ionic
species of opposite charge is sprayed onto the charged substrate.
Dip coating
Coating is applied to the tablet cores by dipping them into the coating liquid
Vacuum film coating
Vacuum film coating is a new coating procedure that employs a specially designed baffled pan
Equipments
Three general types of equipments are available
1.Standard coating pan e.g., Pellegrin pan system
Immersion sword system
Immersion tube system
2.Perforated pan system e.g.,Accela cota system
Hicoater system
Glattcoater system
Driacoated system
3.Fluidized bed coater
Process parameters
Air capacityThis value represents the quantity of water or solvent that can be removed during the coating process which
depends on the quantity of air flowing through the tablet bed, temperature of the air and quantity of water that
the inlet air contains.
Coating composition/compound
The coating contains the ingredients that are to be applied on the tablet surface and solvents which act as carrier
for the ingredients.
Tablet surface area
It plays an important role for uniform coating. The total surface area for unit weight decreases significantly
from smaller to larger tablets. Application of a film with the same thickness requires less coating composition.
Equipment efficiency
Tablet coaters use the expression coating efficiency a value obtained by dividing the net increase in coated
tablet weight by the total nonvolatile coating weight applied to the tablet. Ideally 90-95 % of the applied film
coating should be on the tablet surface.
Coating efficiency for conventional sugar coating is much less and 60% would be acceptable.
Key Wards
The sugar coating involves several steps like, sealing, subcoating, colour coating and printing.
Sugar coating process yields elegant and highly glossed tablet.
Newer techniques utilize spraying systems and varying degree of automation to improve coating efficiency and
product uniformity.
Film coating is deposition of a thin film of polymer surrounding the tablet core.
Film coating is more favored than sugar coating because weight increase is 2-3%, single stage process, easily
adaptable to controlled release, it retains colour of original core, high adaptability to GMP, automation is
possible, etc.
Accela cota and fluidized bed equipments are widely used for film coating.
Basic formula is obtained from past experience or from literature and modifications are made accordingly.
Common modifications are to alter polymer-to-plasticizer ratio or addition of different plasticizer/polymer.
Experimentation of this type can be best achieved by fractional factorial study.
Materials used in film coating include film formers, solvents, plasticizers, colourants,
opaquant-extenders, surfactant, anti oxidant, etc.
Widely used film formers are Hydroxy Propyl Methyl Cellulose (HPMC),Methyl Hydroxy Ethyl Cellulose
(MHEC), Ethyl Cellulose (EC), Hydroxy Propyl Cellulose (four grades available i.e. K15, K-30, K-60and K90), Sodium(HPC), Povidone carboxy methyl cellulose, Polyethylene glycols (PEG) and Acrylate polymers
(Eudragit, EudragitRL, EudragitRS, EudragitE) are used for film coating. EudragitL & S are used for
enteric coating. EudragitRL, EudragitRS, EudragitS are available as organic solution and solid while
EudragitL and EudragitE are available as organic, solid or aqueous dispersion. Quality of film can be
modified by plasticizer. Commonly used plasticizers include PG, glycerin, low molecular weight PEG, castor
oils, etc. Castor oil and spans are more used for organic solvent based coating solution while PE and PEG are
used for aqueous coating. FD & C or D & C certified colourants are used. Lakes are choice for film coating as
they give reproducible results. Opaspray (opaque colour concentrate for film coating) and Opadry (complete
film coating concentrate) are promoted as achieving less lot-to-lot variation. Colourants are expensive and
higher concentration is required.
So materials like titanium dioxides, silicates, and carbonates are used to provide more pastel colours and
increase film coverage.
Enteric Coating -Enteric coating is used to protect tablet core from disintegration in the acid environment of
stomach to prevent degradation of acid sensitive API, prevent irritation to stomach by certain drugs, delivery of
API into intestine, to provide a delayed release components for repeat action, etc.
Several kinds of enteric layer systems are available like one layer system and two-layer system. Polymers used
for enteric coating are cellulose Acetate Phthalate (CAP), Acrylates (EudragitL and EudragitS, Hydroxy
Propyl Methyl Cellulose Phthalate (HPMCP50, HPMCP55 & HPMCP 55s) and polyvinyl acetate phthalate
Enteric sugar coating
Here sealing coat is modified to comprise one of the enteric polymers in sufficient quantity to pass the enteric
test for disintegration. The sub coating and subsequent coating steps are then as for conventional sugar coating.
Enteric polymers are capable of forming a direct film in a film coating process. Sufficient weight of enteric
polymer has to be used to ensure an efficient enteric effect.
Enteric coating can be combined with polysaccharides, which are enzymatically degraded in colon. For example,
Cyclodextrin & Galactomannan
Controlled release coating:
Polymers like modified acrylates, ethyl cellulose, etc are used for the same.
Tablet Manufacturing
Problems in Tablet
Contents
1 Introduction
1.1 Capping
1.2 Lamination / Laminating
1.3 Chipping
1.4 Cracking
1.5 Sticking / Filming
1.6 Picking
1.7 Binding
1.8 Mottling
1.9 Double impression
2 Problems and remedies for tablet coating
2.1 Blistering
2.2 Chipping
2.3 Cratering
2.4 Picking
2.5 Pitting
2.6 Blooming
2.7 Blushing
2.8 Colour variation
2.9 Infilling
2.10 Orange peel/Roughness
2.11 Cracking/Splitting
3 Key Phrases
Introduction
An ideal tablet should be free from any visual defect or functional defect.
In Manufacturing technology a lot of advanchment happened in last 50 years,in technoly, in the process and in
the materials being used but problems has not been decreased.
Demands of Quality have increased in one hand on the other hand the process is a complex one.
Manufacturing pharmacist often encounters number of problems during manufacturing.
Majority of visual defects are due to inadequate fines or inadequate moisture in the granules ready for
compression or due to faulty machine setting. Functional defects are due to faulty formulation.
Knowledge of granulation processing and tablet presses may help solving the problems
The Imperfections
The imperfections or VISUAL DEFECTS may happen for the following factorsTableting Process
Excipient
Machine
Process Related Defects
i) CAPPING: It is due air-entrapment in the granular material.
ii) LAMINATION: It is due air-entrapment in the granular material.
iii) CRACKING: It is due to rapid expansion of tablets when deep concave punches are used.
Excipient Related Defects
iv) CHIPPING: It is due to very dry granules
v) STICKING
vi) PICKING
vii) BINDING
viii) MOTTLING- more than one factor-Due to a coloured drug, which has different colour than the rest of the
granular material? (Excipient- related); improper mixing of granular material (Process-related); dirt in the
granular material or on punch faces; oil spots by using oily lubricant.
Machine Related Defect
ix) DOUBLE IMPRESSION -due to free rotation of the punches.
Causes And Remedies

Capping
Capping is the term used, when the upper or lower segment of the tablet separates horizontally, either
partially or completely from the main body of a tablet and comes off as a cap, during ejection from the tablet
press, or during subsequent handling.
Reason: Capping is usually due to the airentrapment in a compact during compression, and subsequent
expansion of tablet on ejection of a tablet from a die.
CAUSES AND REMEDIES OF CAPPING RELATED TO FORMULATION
CAUSES AND REMEDIES OF CAPPING RELATED TO MACHINE-DIES, PUNCHES AND TABLET
PRESS
Lamination / Laminating
Definition: Lamination is the separation of a tablet into two or more distinct horizontal layers.
Reason: Airentrapment during compression and subsequent release on ejection.
The condition is exaggerated by higher speed of turret.
CAUSES AND REMEDIES OF LAMINATION RELATED TO FORMULATION (GRANULATION) and
Lamination related to MACHINE (Dies, Punches and Tablet Press)
Chipping
Definition: Chipping is defined as the breaking of tablet edges, while the tablet leaves the press or during
subsequent handling and coating operations.
Reason: Incorrect machine settings, specially mis-set ejection take-off.
CAUSES AND REMEDIES OF CHIPPING RELATED TO FORMULATION (GRANULATION) ARE AS
FOLLOWS
CAUSES AND REMEDIES OF CHIPPING RELATED TO MACHINE (DIES, PUNCHES AND TABLET
PRESS)
Cracking
Definition: Small, fine cracks observed on the upper and lower central surface of tablets, or very rarely on the
sidewall are referred to as Cracks.
Reason: It is observed as a result of rapid expansion of tablets, especially when deep concave punches are used.
HUA
CAUSES AND REMEDIES OF CRACKING RELATED TO FORMULATION (GRANULATION)
CAUSES AND REMEDIES OF CRACKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET
PRESS)
Sticking / Filming
Definition: Sticking refers to the tablet material adhering to the die wall.
Filming is a slow form of sticking and is largely due to excess moisture in the granulation.
Reason: Improperly dried or improperly lubricated granules.
CAUSES AND REMEDIES OF STICKING RELATED TO FORMULATION (GRANULATION)
CAUSES AND REMEDIES OF STICKING RELATED TO MACHINE (DIES, PUNCHES AND
PRESS)
TABLET
Picking
Definition: Picking is the term used when a small amount of material from a tablet is sticking to and being
removed off from the tablet-surface by a punch face.
The problem is more prevalent on the upper punch faces than on the lower ones. The problem worsens, if
tablets are repeatedly manufactured in this station of tooling because of the more and more material getting
added to the already stuck material on the punch face.
Reason: Picking is of particular concern when punch tips have engraving or embossing letters, as well as the
granular material is improperly dried.
CAUSES AND REMEDIES OF PICKING RELATED TO FORMULATION (GRANULATION)
CAUSES AND REMEDIES OF PICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET
PRESS)
Binding
Definition: Binding in the die, is the term used when the tablets adhere, seize or tear in the die. A film is
formed in the die and ejection of tablet is hindered. With excessive binding, the tablet sides are cracked and it
may crumble apart.
Reason: Binding is usually due to excessive amount of moisture in granules, lack of lubrication and/or use of
worn dies.
CAUSES AND REMEDIES OF BINDING RELATED TO FORMULATION (GRANULATION)
CAUSES AND REMEDIES OF BINDING RELATED TO MACHINE (DIES, PUNCHES AND TABLET
PRESS)
Mottling
Definition: Mottling is the term used to describe an unequal distribution of colour on a tablet, with light or
dark spots standing out in an otherwise uniform surface.
Reason: One cause of mottling may be a coloured drug, whose colour differs from the colour of excipients used
for granulation of a tablet.
CAUSES AND REMEDIES OF MOTTLING
Double impression
Definition: Double Impression involves only those punches, which have a monogram or other engraving on
them.
Reason: At the moment of compression, the tablet receives the imprint of the punch, the punch rotates and at
this point, the punch may make a new impression on the bottom of the tablet, resulting in Double Impression.
CAUSES AND REMEDIES OF DOUBLE IMPRESSION
Blistering
Definition: It is local detachment of film from the substrate forming blister.
Reason: Entrapment of gases in or underneath the film due to overheating either during spraying or at the end of
the coating run.
Chipping
Definition: It is defect where the film becomes chipped and dented, usually at the edges of the tablet.
Reason: Decrease in fluidizing air or speed of rotation of the drum in pan coating.
Cratering
Definition: It is defect of film coating whereby volcanic-like craters appears exposing the tablet surface.
Reason: The coating solution penetrates the surface of the tablet, often at the crown where the surface is more
porous, causing localized disintegration of the core and disruption of the coating.
Picking
Definition: It is defect where isolated areas of film are pulled away from the surface when the tablet sticks
together and then part.
Reason: Conditions similar to cratering that produces an overly wet tablet bed where adjacent tablets can stick
together and then break apart.
Pitting
Definition: It is defect whereby pits occur in the surface of a tablet core without any visible disruption of the
film coating. Reason: Temperature of the tablet core is greater than the melting point of the materials used in the
tablet formulation.
Blooming
Definition: It is defect where coating becomes dull immediately or after prolonged storage at high temperatures.
Reason: It is due to collection on the surface of low molecular weight ingredients included in the coating
formulation. In most circumstances the ingredient will be plasticizer.
Blushing
Definition: It is defect best described as whitish specks or haziness in the film.
Reason: It is thought to be due to precipitated polymer exacerbated by the use of high coating temperature at or
above the thermal gelation temperature of the polymers.
Colour variation
Definition: A defect which involves variation in colour of the film.
Reason: Alteration of the frequency and duration of appearance of tablets in the spray zone or the size/shape of
the spray zone.
Infilling
Definition: It is defect that renders the intagliations indistinctness.
Reason: Inability of foam, formed by air spraying of a polymer solution, to break.
Orange peel/Roughness
Definition: It is surface defect resulting in the film being rough and nonglossy. Appearance is similar to that of
an orange.
Reason: Inadequate spreading of the coating solution before drying.
Cracking/Splitting
Definition: It is defect in which the film either cracks across the crown of the tablet (cracking) or splits around
the edges of the tablet (Splitting)
Reason: Internal stress in the film exceeds tensile strength of the film.
Key Wards
During tablet manufacture, an industrial pharmacist usually encounters many problems. Solving these problems
requires an in-depth knowledge of tablet-formulation as well as machine-operating processes.
Capping and Lamination are the defects arising as a result of air-entrapment in the granular material.
Chipping is a defect related arising due to very dry granules.
Cracking is due to rapid expansion of tablets, when deep concave punches are used.
Sticking, Picking and Binding are the imperfections related to more amount of binder in granules.
Mottling is an imperfection arising due to more than one factor: a coloured drug, dirt in granules or the use of an
oily lubricant.
Double-Impression is related to a machine defect: it is caused by the free rotation of punches that have some
engraving on the punch-faces.
Coating defects
Blistering is related to entrapment of gases in or underneath the film due to overheating either during spraying
or at the end of the coating run. Use of mild drying conditions can solve this problem.
Chipping is related to higher degree of attrition associated with the coating process. Increase in hardness of the
film by increasing the molecular weight grade of polymer can solve this problem.
Cratering is related to penetration of the coating solution into the surface of the tablet, often at the crown where
the surface is more porous, causing localized disintegration of the core and disruption of the coating. Decrease
in spray application rate and use of optimum and efficient drying conditions can solve this problem.
Pitting is defect in which temperature of the tablet core is greater than the melting point of the materials used in
tablet formulation. Dispensing with preheating procedures at the initiation of coating and modifying the drying
(inlet air) temperature can solve this problem.
Blooming or dull film is generally because of higher concentration and lower molecular weight of plasticizer.
So use lower concentration and higher molecular grade of plasticizer.
Blushing/Whitish specks/Haziness of the film is related to precipitation of polymer exacerbated by the use of
high coating temperature at or above the thermal gelation temperature of the polymers.
Colour variation is because of improper mixing, uneven spray pattern, insufficient coating or migration of
soluble dyes during drying. Geometric mixing, mild drying conditions and reformulation with different
plasticizers can solve this problem.
Infilling is because of bubble/foam formation during air spraying of a polymer solution. Addition of alcohol or
use of spray nozzle capable of finer atomization can solve this problem.
Orange peel/Roughness is related to inadequate spreading of the coating solution before drying. So decrease in
viscosity of coating solution can counter this defect.
Cracking is seen when internal stresses in the film exceeds tensile strength of the film. This is common with
higher molecular weight polymers or polymeric blends. So use lower molecular weight polymers or polymeric
blends
Quality Control Tests
For Tablets
Contents
1 Official Standards as per I.P. / B.P. / U.S.P. /EU
2 Non Compendial Standards
2.1 Hardness tests/ Crushing strength
2.2 Friability
2.3 Tests for coated tablets
3 In Process Quality Control
4 Key Phrases
Official Standards
COMPARISON OF DIFFERENT PHARMACOPOEIAL QUALITY CONTROL TESTS BRITISH
PHARMACOPOEIA BP
Official Standards as per I.P. / B.P. / U.S.P.
TABLE: 54. COMPARISON OF DIFFERENT PHARMACOPOEIAL QUALITY CONTROL TESTS
PHARMACOPOEIAS TYPE
OF TESTS TO BE PERFORMED
TABLET
BRITISH
PHARMACOPOEIA
Content of active ingredients

Disintegration
For all tablets
Uniformity of content
Labeling
Uncoated
tablet
Disintegration
Uniformity of weight
test
Effervescent Disintegration
tablet
test
Disintegration
test
Coated tablet
Gastro
resistant
tablet
Disintegration test
Modified
release tablet
Tablet for use
in mouth
INDIAN
PHARMACOPOEIA
Soluble tablet
Disintegration
Dispersible
tablet
Disintegration test
Uniformity of dispersion
Uncoated
tablet
Uniformity of container content

Content of active ingredient
Uniformity of content
Disintegration test
test
Enteric
Disintegration test
coated tablet
Dispersible
tablet
Uniformity of dispersion
Disintegration
Soluble tablet Disintegration test

Effervescent Disintegration/ Dissolution / Dispersion
tablet
test
Bulk density /Tapped density of powder
Powder fineness
Loss on drying
Physical tests Disintegration test
UNITED
STATES applicable to Tablet friability
PHARMACOPOEIA
tablet
Dissolution test
formulation Drug release testing
Uniformity of dosage form
Container permeation test
Labeling of inactive ingredients
Non-compendial Standards
Measurement of mechanical properties is not covered pharmacopoeial monograph. There are also a number of
tests frequently applied to tablets for which there are no pharmacopoeial requirement but will form a part of a
manufacturers own product specification.
Hardness tests/ Crushing strength
The test measures crushing strength property defined as the compressional force applied diametrically to a
tablet which just fractures it.
Friability (Official in USP)
Coating, packaging, transport, which are not severe enough to break the tablet, but may abrade the small
particle from tablet surface.
Tests for coated tablets

Water vapor permeability
Film tensile strength
Coated tablet evaluations:
i)Adhesion test with tensile-strength tester: Measures force required toe peel the film from the tablet surface.
ii)Diametral crushing strength of coated tablet: Tablet hardness testers are used. This test gives information on
the relative increase in crushing strength provided by the film
iii) Temperature and humidity may cause film defects. Hence studies are to be carried out.
iv) Quantification of film surface roughness, hardness, & colour uniformity. Visual inspection or instruments
are used.
In Process Quality Control
The control of the tableting process in production is concerned with the following :
I. Weight of tablet Single pan electric balance.
II. Crushing strength /hardness Controls friability and disintegration time.
III. Tablet thickness Very thick tablet affect packaging particularly into blisters.
IV. Disintegration time.
V. Friability
As a part of Current Good Manufacturing Practice (cGMP), the production run is monitored under control chart.
At regular interval (10 15minutes) the operator must sample specified number of tablets, weigh them
individually, check thickness, crushing strength and all the properties as mentioned above
Key Ward
USP mentions some of the quality control tests to be performed before the powder is compressed. e.g., powder
fineness, density. etc.
Friability is official test as per USP.
At regular interval (10 15minutes) during the course of manufacturing the operator must sample specified
number of tablets for testing

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Tablet

VARIOUS TYPES OF TABLETS

Excipients and their functions

i)Organic materials - Carbohydrate and modified carbohydrates.

Glidants improve the flow property of material/granules.

Colour-API should be colourless

4 Merits over wet granulation process

Three Steps Operation

AdvantagesShort processing time

Fluidized bed granulator

Steam granules are more spherical,

viii) High resistance to cracking

Causes And Remedies

Content of active ingredients

Uniformity of container content

Soluble tablet Disintegration test

Tests for coated tablets

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