Lesson - 9 Tablets-I Introduction

Lesson - 9

Tablets-I

Introduction

-Dr Ajay Semalty

Department of Pharmaceutical Sciences,

H.N.B Garhwal University (A Central University)

Srinagar Garhwal-246174

Learning outcomes

After learning this module, you will be able to understand

What is tablet and what are its advantages and disadvantages

Types and Classification of tablets.

What is granulation, why it is important, and how it is done for tablet

manufacturing

Lesson Plan

Definition and ideal properties

Advantages, Disadvantages, and Classification of tablets.

Types and classification of excipients

Basic steps of Formulation of tablets,

Granulation methods: process, factors and equipment

o Wet Granulation (WG)

o Dry Granulation (DG)

Module 9 Tablets – I 2

MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal

University (A Central University) Srinagar (Garhwal) Uttarakhand, India

Tablets

Tablets are the most common and convenient dosage form. About 70%

of the total medicines are in Tablet form.

“Tablets are solid, flat or biconvex dishes, unit dosage form,

prepared by compressing a drug or a mixture of drugs, with or

without diluents.”

Do you know what unit dosage form is? The dosage form which

deliver one single unit of dosage of the drug. Tablet is a unit

dosage form. Dear learners can you let me know any other

example of unit dosage form? And multi-unit dosage form?

Ideal Characteristics of Tablets

A tablet should have the following ideal properties.

Elegant product identity

Free of defects like chips, cracks, discoloration, and

contamination

Sufficient strength (to withstand mechanical shock and

agitation during its production, packaging, shipping and

dispensing.

Chemical stability: shelf life

Physical stability: color, physical integrity like shape etc.

Release the drug in desired and reproducible manner.

Advantages of Tablet Dosage Forms

Tablet has a number of advantages, one of the major advantage

over capsule, is that tablet is an essentially tamperproof doses form.

Other potential advantages of tablets are as followed:




These are the unit dosage forms which offer the greatest

flexibility (with respect to doses) of all oral doses forms.

Its cost is lowest of all oral dosage forms.

These are the lightest and most compact of all oral doses

forms.

These are in general the easiest and cheapest to package and

ship of all oral dosage forms.

Product identification is simplest and cheapest, requiring no

additional processing steps.

These may provide the greatest ease of swallowing with least

tendency for ''hang-up' above stomach, especially when coated,

provided that tablet disintegration is not excessively rapid.

These are better suited to large scale production than other unit

oral forms.

These have best combined properties of chemical, mechanical,

and microbiological stability of all the oral forms.

Objectionable odor and bitter taste can be masked by coating

technique.

Generally more stable than liquids with longer expiration

dates.

Release rate of the drug from tablet can be tailored to meet

pharmacological requirements.

Disadvantages of Tablet Dosage Form

Drugs which are destroyed in stomach cannot be prepared in

tablets e.g proteins/peptides etc.

Drugs with bitter taste or odour cannot be formulated in tablets

without modification (capsules may be tried)

Peak and valley effect in plasma time concentration curve for




IR dosage forms

The drug with too short half life can not be formulated.

Classification of Tablets (USP)

I. Immediate-release tablet

Disintegrating tablet (conventional tablet)

Chewable tablets

Effervescent tablets

Sublingual and Buccal tablets

Lozenges

II. Modified-release tablet

Extended-release

Delayed-release

I. Immediate-release tablet

Conventional/Disintegrating tablet

It is the most common type of tablets. It is released rapidly after

administration. It is intended to be swallowed and undergo

disintegration and dissolution in the GIT. The commonly required

excipients in these are filler (with low dose drug), disintegrant,

binder, glidant, lubricant and antiadherent.

Chewable tablets

These tablets are designed for children and elderly people and can be

taken without water. The tablet is to be chewed and thus

mechanically disintegrated in the mouth, so that no disintegrant is

included in its composition. Its important excipients are Flavoring,

sweetening and coloring agents. e.g. Chewable Antacid tablets

Effervescent tablets

The effervescent tablet is dropped into a glass of water before




administration during which Carbon di oxide (CO2) is liberated. It

can be taken without water. It facilitates rapid tablet disintegration

and drug dissolution. The special packaging is needed to avoid

exposure of these tablets to moisture. It is used to obtain rapid

drug action e.g Effervescent antacid tablets. The important

excipients of these tablets are acid with alkali effervescing

compound, flavoring, and coloring agents

Sublingual and Buccal tablets

They are used for drug release in mouth for systemic delivery by

avoiding first pass metabolism. Here the drug diffuses into the

blood, directly through tissues under the tongue in case of

sublingual tablets and through oral mucosa in case of buccal

tablets. It facilitates rapid tablet disintegration and drug

dissolution. For example, Nitroglycerin sublingual tablet exerts its

action within two minutes for rapid relief of "Angina pectoris"

attack, because the sublingual area is rich in blood supply.

Nitroglycerine suffers from first-pass metabolism if taken orally.

Lozenges

These are the tablets which dissolve slowly in the mouth. These are

used for local medications in the mouth or throat, e.g. local

anesthetics, antiseptics and antibiotics and for systemic drug

uptake. In the lozenges no disintegrant is included. Other

additives (binder and filler) must have pleasant taste.

Modified-Release Tablets

According to the USP/NF the term 'modified release dosage forms' is

defined as “one for which the drug release characteristics of

time course and/or location are chosen to accomplish

therapeutic objectives not offered by the conventional dosage

forms.”




Classification

Modified release dosage forms may be classified into two types.

Extended-release

Delayed release

Extended-release Tablets

It is defined as the one that allows at least a twofold reduction in the

dosing frequency as compared to that of conventional (immediate

release) dosage form. For example: controlled release or sustained

release tablets

Delayed release Tablets

“the dosage form that releases a discrete portion or portions of drug at

a time (or times) other than promptly after administration.” -

USP

Enteric coated tablets are the example of delayed release dosage forms

Fig. Plasma Concentration Time profile Curve for Immediate release and Modified

Release dosage form




Excipients

“An excipient is an inactive substance used as a carrier for the active

ingredients of a medication”.

The excipients are selected on the basis nature of drug, nature of other

excipients, compatibility with drug and other excipients and the

desired release or performance characteristics of tablet.

Classification of excipients

A. Primary Excipients: The primary excipients impart satisfactory

compression characteristics to the formulation. E.g. diluents,

binders, glidants and lubricants

B. Secondary Excipients: The secondary excipients give additional

desirable physical characteristics to the finished tablet. e.g.

disintegrants, coloring, flavoring and sweetening agents.

Filler / diluent

Filler or diluents add bulk to the tablet for compression and easy

handling. Diluents weigh 10 to 20 fold of the dosage of API. E.g.

Glucose, Sodium chloride, Sucrose, Mannitol (chewable tablet, freely

soluble in water, cool taste), Microcrystaline Cellulose (excellent

compression property, highly stable and disintegrating property).

Binder

Do you remember why we need cement to build a house? Binder is

added for cohesive strength after compression. e.g. Aacacia

mucilage, Glucose, Gelatin, providone (PVP), Starch mucilage




Disintegrant

Figure: Importance of disintegration

Tablet is needed to be dissolved in GI fluid for getting absorbed

and for getting dissolved it is needed to be disintegrate in smaller

particles. The disintegrants make the tablet to break down in

smaller particles after oral ingestion.

E.g. crospovidone, croscarmellose sodium, sodium starch glycolate

etc.

Glidant

Glidants are used for reducing the friction between particles. Glidants

improve the flow properties of tablet granules and powders during

processing (mixing, moving for compression etc). e.g. Corn starch,

Talc, Colloids silicates.

Lubricant

Lubricants ensure that tablet possess a smooth surface. Lubricants act

by reducing the friction between tablet wall and die walls. e.g.

Talc, stearic acid, silicates.

Antiadherent




The antiadherents stop the powder from sticking to the equipment as

the tablet is being made. Exp- Talc, Magnesium stearate, Starch

derivatives.

Miscellaneous

Colors, flavors etc.

Manufacturing Tablet

Tablet is the most complex Dosage form. The tablet manufacturing is

an art as well as a science. It consists of the two important steps:

Step1: Blending of drug with excipients (mixing and granulating)

and;

Step 2: compression (by punches onto die cavity)

Direct compression (skipping granulation) may be practiced for drug

and excipients with good compatibility and low stickiness (but not

always feasible)

Mixing and granulation

“Granulation is the process of combining particles together by creating

bonds between them”

The definition is looking typical? Let me make it simpler for you

Have you seen preparation of besan laddu?

Coarse besan or fine besan?

Why the coarse besan is needed ? Because it has the good binding.

Objectives of granulation

Conversion Powder to granules is granulation and it is performed with

the following objectives.




To assure an even distribution of the active compound in the

final tablet

To ensure content uniformity due to narrow size range

To increase the density for easy storage and shipment

To improve flow and compaction

There are several different methods of granulation. The most popular,

which is used by over 70% of formulation in tablet manufacture is

wet granulation. Dry granulation is another method used to form

granules.

Mechanism of granulation

The granulation occurs due to following events.

Wetting

Nucleation

Coalescence/ growth

Consolidation

Attrition/ breakage

By solid bridges/ chemical reaction/ sintering/ crystalization/

deposition of particles/ adhesive and cohesive forces of High

viscous binders

Wet Granulation

Imagine preparing dough for chapati

What do you need for that?

Yes…water in optimum amount

“using a liquid binder (in optimum amount) to lightly agglomerate the

powder mixture”

Wet granulation is a process of using a liquid binder to lightly

agglomerate the powder mixture. The amount of liquid has to be




properly controlled, as over-wetting will cause the granules to be too

hard and under-wetting will cause them to be too soft and friable.

Aqueous solutions have the advantage of being safer to deal with than

solvent based systems.

Fig. The wet Granulation Process

Fluidized bed granulation (FBG)

FBG is a multiple step wet granulation process. It is All in one

process: pre-heat, granulate, and dry the powders. It allows close

Weigh active ingredient and

excipients

Add the liquid binder to the powder blend and mix thoroughly

Screen the damp mass through a

mesh to get pellets/granules

Drying

Again passed through a sieve (Finer one than

earlier used)

Granules




control of the granulation process.

It’s a huge equipment and it is used in mixing/granulation, drying and

film coating. The lower part contains a perforated basket of SS which

contains the mixture to be granulated. The air enters from the bottom

of the perforated basket. The particles are uplifted with the stream of

air. The fountain like movement of particles is called Wurster process.

The granulating fluid is sprayed (Top/bottom or tangential spray). At a

stage the bed of solid become fluidized and behaves like fluid. Hence

it is called FBG or FBD.

Factors affecting granulation

Blend factors: Particle size of the drug and excipients

Binder factor: Type, Volume and concentration of binder

Granulation process factor: granulation time, equipment and

drying rate

Dry Granulation

Dry granulation is done for moisture and heat sensitive products and

the products which are not compressed well after WG. It is done

without the use of liquid binder. It is simpler than wet granulation

and is a low cost technique. The DG involves creating granules by

light compaction of the powder blend under low pressures. The

prepared slugs are broken into granules.




Process of DG

Milling (Cutter Mill)

Mixing (Sigma Blade Mixer)

Slugging

Screening (Oscillating Granulator)

Mixing with Disintegrant and Lubricant

Compression

Equipment for granulation

Roller compaction, extrusion spheronization, spray drying

equipment

Low shear/ High shear granulators

Fluidized Bed Dryer (FBD)

Continuous spouted bed

High shear granulator (with the help of counter current

operating blades) E.g. RMG (Rapid Mixer Granulator).

New advanced techniques

Steam Granulation,

Melt Granulation Granulation,




Moisture Activated Dry Granulation (MADG),

Moist Granulation Technique (MGT),

Thermal Adhesion Granulation Process (TAGP),

Extrusion-spheronization (ES),

Continuous twin screw wet granulation (cTSWG)

Table: The advanced techniques in Granulation

Technique Description

Steam Granulation Modification of wet granulation; steam is

used as a binder in place of water

Melt Granulation / Thermoplastic

Granulation

Granulation is done by addition of meltable

binder (binder is in solid state at room

temperature but melts in the temperature

range of 50 – 80˚C).

Moisture Activated Dry Granulation

(MADG)

Minimal moisture addition, distribution and

agglomeration. No drying step is required.

Water distribution is via high shear mixer,

or low-shear mixer with highly atomized

water spray

Moist Granulation Technique (MGT) Works on the principle of MADG. A small

amount granulating fluid is added to

activate dry binder and to facilitate

agglomeration. Then a moisture absorbing

material like Microcrystalline Cellulose

(MCC) is added to absorb any excess

moisture.

Thermal Adhesion Granulation

Process (TAGP)

Used for preparing direct tableting;

performed under low moisture content or

low content of pharmaceutically acceptable

solvent by subjecting a mixture containing

excipients to heating at a temperature in the

range from about 30ºC to 130ºC in a closed

system under mixing by tumble rotation




until the formation of granules.

Foam Granulation Liquid binders are added as aqueous foam.

Extrusion-spheronization

(ES)

Extrusion (forming a raw material into a

product of uniform shape and density by

forming it through an orifice or die under

controlled conditions) followed by

spheronization (a rapid and flexible process

where wet extruded mass is converted to

small spheres) through multi step

processing

Continuous twin screw wet

granulation (cTSWG)

Advanced technique of ES; Preblend of

crystalline poorly soluble API and

amorphous polymer is charged into Twin

screw granulator

Take Away Message

Tablet are unit dosage forms which are the most common, cost

effective, and convenient dosage forms

Tablets may be of different types: IR or modified release.

Various excipients with different functions are needed

Mixing, granulation and compression are three important steps in

manufacturing of tablets.

Wet and dry granulation are two methods of granulation

Further Readings

• Aulton ME (ED), Pharmaceutics: The science of Dosage form design,

II edn, Churchill Livingstone, London, 2002.

• Semalty et al., Essentials of Pharmaceutical Technology, II Edn, 2018,

Pharma Med press, Hyderabad, India

• Qiu Y, Chang Y and Zhang GZ (Exe. Eds), Developing solid oral

dosage forms: Pharmaceutical theory and practice, Elsevier, 2009.




References/ Credits

• USP-40

• Semalty et al., Essentials of Pharmaceutical Technology, II Edn, 2018,

Pharma Med press, Hyderabad, India

Documents

Lesson - 9 Tablets-I Introduction