Tablet Ingredients

Pharmaceutical Technology I PHARM 2322 By: 1008-1873

Excipients
Inactive ingredients which play a major role

in formulation development. There are many type of excipients including:

Antiadherent

Diluents
Binders Glidants

Colourants
Flavourings Coatings Disintegrants etc.

Why are excipients needed in tablet formulation?

To ensure the tableting operation can run

satisfactorily. To ensure that tablets of specified quality are prepared.

Do all tablets contain the same ingredients?

Not all tablets contain the same ingredients.

If no, why?
A tablet is a combination of ingredients that is

compressed into a solid mass. Diff. tablet contains diff. ingredients (API,excipients) depending on: - Route of administration - Form of drug - Intended therapeutic effect

1. Antiadherent
Reduce the adhesion between the powder and the

punches wall and thus prevent particles sticking to the punches. Antiahderents with good hydrophobicity (waterrepelling) prevent finished products from absorbing water. Example: Magnesium Stearate
concentration range of 0.25%-2%. Magnesium stearate exists as plate-like crystals (or lamellae)

stacked together like a deck of cards. As the blending process proceeds, plates continue to shear off and coat adjacent particles of granules, drug or other excipients.

List of antiadherents
Antiadherent Range (%w/w) Comment

Talc
Colloidal silica Stearates

1-5
0.1 0.5 <1

Works with lubricant with excellent antiadherents properties

Does not give satisfactory results due to small surface area Antiadherents with water insoluble lubricant.

2. Binders
To ensure tablets can be formed with the required

mechanical strength. During compacting, binders provide cohesive binding and deformation characteristics necessary for the formation of tablets. Binders form films on the surface of the granules, which can aid in the wetting of hydrophobic API.

 Can be added to a powder in diff. ways.

As dry powder before wet agglomeration As a solution @ solution binder used as agglomeration liquid during wet agglomeration As a dry powder @ dry binder mixed with other ingredients before compaction

Solution binders are generally considered the most

effective. An ideal binder should have good binding properties.

Small in size uniform distribution Low hygroscopicity reduce absorption of moisture Highly plastic properties (high deformability) - to reduce friability

List of binders:
Binder
Starch Paste

Conc. (% w/w) Comment

5-25

- Freshly prepared starch paste is used as a binder. - Its method of preparation is very crucial. - Comparable to Methyl Cellulose. - Used as a binder in either wet or dry granulation processes.

Hydroxypropyl 2-5 Methyl Cellulose (HPMC)

Other example of binder: Starch, sucrose, gelatin Polyethylene Glycol (PEG) Polyvinyl Pyrrolidone (PVP) Pregelatinized Starch (PGS)

3. Diluents
Inactive ingredients that are added to tablets in

addition to the active drug. Increase the bulk volume of the active so that the size of the tablet is suitable for handling. Requirements of ideal diluent:
Chemically inert
Non-hygroscopic Biocompatible Possess good biopharmaceutical properties(e.g water soluble) Possess good technical properties (compactibility) Have an acceptable taste Cheap

Example of diluents:
Diluents Lactose Advantages Good compressibility Soluble in water Pleasant taste Non-hygroscopic Non reactive Highly compressible Exhibits binding properties Possess disintegrant activity Biocompatible Chemically inert Limitation Slowest dissolving sugar Some people have lactose intolerance

Microcrystall ine cellulose (MCC) (20-90% w/w)

It is water insoluble. MCC is expensive. Hygroscopic

Other example: dicalcium phospate dihydrate -Insoluble in water and non-hygroscopic but is hydrophillic.

4. Sweetener
Improve the taste of chewable tablets.

Sucralose excellent sweetness, non-cariogenic,

low calorie, wide and growing regulatory acceptability but relatively expensive.

Natural sweeteners

Artificial sweeteners

Sorbitol
Non-cariogenic, non-calorific appropriate for paediatric formulations But lower sweetness intensity than sucrose (so you need more) Can cause diarrhoea

Saccharin

Restricted regulatory acceptability Bitter after taste Hypersensitivity reactions; mainly dermatologic Paediatrics with allergy to sulphonamides should avoid saccharin

Sucrose
Soluble in water (vehicle) Colourless Stable (pH 4-8) Increases viscosity; Arguably the best taste/mouthfeel overall But cariogenic and calorific avoid in paediatrics

Aspartame
Source of phenylalanine possibly an issue for phenylketoneurics Aspartame has been blamed for hyperactivity in children but as yet unproven

Lactose
Some people may have lactose intolerance

Cyclamate
Carcinogenic

5. Sorbents
Agents that can retain large quantities of liquids. Used when there is a need to add a liquid or semisolid

ingredient in the formulation. Commonly used adsorbents:

anhydrous calcium phosphate Starch magnesium carbonate kaolin magnesium silicate magnesium oxide silicon dioxide

 Ideal characteristic of sorbent:

very small in size of particle High adsorption capacity

Sorbent Silica Microcrystalline cellulose

Particle size Adsorption Less than 10 can adsorb up to 1.6 ml of m liquid per gram Larger than silica Lower adsorptive capacity 1/10 of a ml per gram than silica.

6.Preservatives
Substances that helps to control or inhibit growth of

microorganisms or fungi. Ideal characteristics:

Do no interact with the API Low toxicity

Stable and effective over wide pH

2 types of preservative:

anti-fungal preservatives II. anti-microbial preservatives

I.

List of preservatives
Preservatives Paraben Esters. (methyl, ethyl, propyl, isopropyl, butyl, isobutyl). Typical use concentrations 0.1%-0.3%. Methyldibromo glutaronitrile. Typical use concentrations 0.02%-0.06%. Used in combination with phenoxyethanol. Advantages Low toxicity. Used in food and pharmaceuticals. Stable and effective over a wide pH range. Approved worldwide in personal care in all applications. Disadvantages Low water solubility (except sodium esters) Slightly weak antibacterial activity. Incompatible with some proteins and in some non-ionic emulsifiers. Slightly weak against fungi. Unstable above pH 8. Sensitisation and irritation issues.

Excellent preservative. Excellent antibacterial activity. Compatible with nonionics and proteins.

7. Flavours
Commonly used to improve the taste of chewable

tablets as well as mouth dissolved tablets. 2 types of flavourings:

Water soluble: mannitol, lactose, saccharin, sucrose II. Volatile, oil : fennel oil, rose oil
I.

Example of flavour:
Mannitol
Advantages Disadvantages

Possess slow solubility and mild Requires high lubricant content cooling sensation in mouth. Can be used in vitamin Exhibits poor flow properties. formulation Free from grittiness. Most expensive sugar used as a tablet diluent

Possesses low caloric value

Noncariogenic.

Water soluble.

8.Colours
To increase the patients compliance or for

identification of the formulation. Colouring is often accomplished during coating or prior to compaction. Usually the colourants are added in the form of insoluble powder or in the form as liquid in the granulation liquid. Examples of colourants are: FD&C and D &C dyes and lakes.

 Dyes are generally applied as solution especially in the

granulating agent. Lakes are usually employed as dry powders for colouring. Important advantages in using lakes:
reduced risk of interaction between the drug and

other ingredients. colour development is rapid which reduces processing time.

FD & C COLOUR

COMMON NAME

Red 3 Red 40 Yellow 5

Green 3

Erythrosine Allura red AC Tartrazine

Fast Green

9.Disintegrants
To ensure that the tablet breaks up into small fragments

when in contact with liquid to promote rapid drug dissolution.

Disintegrant Native starch MCC Sodium starch glycolate Croscarmellose Conc. Used (%) 5-10 10-25 2-8 1-5 Comments Probably works by wicking; swelling minimal at the body temp. Strong wicking action; loses disintegrant action when highly compressed. Free flowing powder that swells rapidly on contact with water. Swells on contact with water.

 The requirement placed on the tablet disintegrant

should be clearly defined. The ideal disintegrant has:

Poor gel formation Good hydration capacity Good molding and flow properties

No tendency to form complexes with the drugs

 The tablet breaks to primary particles by one or

more of the mechanisms listed below: By capillary action By swelling of particles Because of heat of wetting Due to disintegrating particle/particle repulsive forces Due to deformation Due to release of gases By enzymatic action

10.Lubricants
Help in smooth ejection of tablet from die cavity,

prevent sticking of powder on punch faces (antiadherence), reduce interparticle friction during compression and, to improve flow of powder blend on the machine and into the die cavity.

 Mechanisms of action:
Fluid lubrication A layer of fluid is located between and separates the

moving surfaces of the solids from each other. Thus, reduces the friction. Boundary lubrication The sliding surfaces are separated by only a very thin film of lubricant. Therefore, the nature of the solid surfaces will affect friction. All substances that can affect the interaction between sliding surfaces can be described as boundary lubricants.

Ideal characteristics of lubricants: - low resistance towards shearing - Able to form a thin layer over the surface covered - Non-Toxic - Chemically Inert - Posses minimal adverse effects on the finished product.
Lubricant
Talc

Conc.used (%)
1-5

Comments
Fine,crytalline powder, widely used as lubricant and diluent.

Mg stearate
Glyceryl behenate

0.2-2
0.5-4

Hydrophobic, variable properties between suppliers.

Hydrophobic, also used as controlled release agent.

11.Coating
For protection of the drug from the surrounding.

improve stability for modifying drug release masking unpleasant taste or odour of the drug improving product appearance increasing the mechanical strength of the product. Film coating Sugar coating Compression coating Gelatin coating (not common)

3 main types:

Features Appearance

Film coating

Sugar coating

- Retains contour of - Rounded with high degree of polish original - Highly colored - Usually not shiny

Weight increase due to coating materials

Logo or break-lines

- 2-3% (because of a thin coat).

- Possible during tablet Compression by tablet punches. Easily adaptable for modified-release

- 50-100%

- Break-lines are not possible; logo is only achieved by printing.

Mostly for immediate release tablets, unless specials treatment during the sealing stage.

Compression coating of tablet: -gained increased interest in the recent years for creating modified-released products. -involves the compaction of granular materials around a preformed tablet core using specially designed tableting equipment.

 Ideal characteristics of coating:

Solubility: good solubility

Viscoscity: low viscoscity for a given conc.

Mechanical prop: adequate strength to withstand the

impact and abrasion encountered in normal handling, polymer chosen must also comply with the relevant regulatory and pharmacopoeia requirements.

12.Glidants
Substance that improves the flow characteristics of a

powder mixture. Ideal characteristics of glidant:

small size so that they can retain with in the small pores of

the granules have a greater surface area. hydrophobic

A Glidant's effect is due to a counter-action to factors

resulting in poor flowability of powders. For instance, correcting surface irregularity, reducing interparticular friction and decreasing surface charge. The result is a decrease in the angle of repose which is an indication of an enhanced powder's flowability.

Glidant Talc

Typical Conc.used (%) 1-5

Comments Fine, crystalline powder, widely used as lubricant and diluent. Has small particle size and large surface area for good flowability; used for adsorbent, anti-tacking agent, disintegrant and glidant. Used as glidant and also as disintegrant. Anionic surfactant, lubricant and wetting agent.

Fumed silicon dioxide

0.1-0.5

Native starch Sodium lauryl sulfate

1-10 0.2-2

Multi-functional excipients:
Talc-lubcricant & diluent

Fumed silicon dioxide- adsorbent, anti-tacking agent,

disintegrant and glidant. Native starch- glidant, disintegrant. Sodium lauryl sulphate- surfactant, lubricant, wetting agent.

Standard compressed tablet

Made by either by:

-Direct compression -Wet granulation -Dry granulation -Double compaction. This tablet will undergo disintegration, dissolution and absorption. Types of excipients:
o o o o o o filler(diluents) disintegrants binder glidant lubricant anti-adherent

 They are formulated as more water insoluble by means of

selecting slow dissolving excipients and thus provides local action for long time period. e.g., antacids and adsorbents.
Drugs that produce systemic action have some

aqueous solubility and designed to disintegrate and dissolve quickly so that the drug can be quickly absorbed and produce systemic action.
Generally, an API exhibits bioavailability depending

upon Biopharmaceutical Class, which is based on water solubility and gastro-intestinal membrane permeability criteria. But, it can be altered by appropriate selection of excipients and processing technology.

Chewable tablet
This medication is that it can be taken at any time or

when water is not available. It is used primarily to accomplish a quick and complete disintegration of tablet. Thus, mechanically disintegrated in the mouth, it is swallowed and dissolves in stomach or intestine.
Types of excipients: flavouring agent colouring agent fillers (diluents)

 Mannitol is normally used as a base due to low

hygroscopy and more importantly, it gives pleasant, cooling sensation. Antacid tablets are invariably prepared as chewable to obtain quick ingestion relief as well as the antacid dose is too large to swallow and the activity is related to particle size.

Effervescent tablet
These tablets are intended to produce effervescence

when they come in contact with the water or liquid. Thus the formulation of these tablets includes organic acid and bicarbonates. Water soluble lubricants are preferred here. Binders are not included in the formulation or rather a very less concentration is employed. Effervescent tablets are prepared by the direct compression or by compaction of the granules; wet granulation method is very seldom used.

 Types of excipients: a flavour colourant a water soluble lubricant (to avoid a film of a hydrophobic lubricant on the surface of water after tablet dissolution)

The End
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