Advanced Pharmaceutical Technology

0510543

Coating of tablets and

multiparticulates
 DEFINITION
• Tablet coating is the application of a coating
material to the exterior of a tablet with the
intention of conferring benefits and properties
to the dosage form over the uncoated variety.

• In its widest sense the technology is also

applicable to multiparticulate systems intended
for modified-release applications.

• To a much lesser extent coatings may also be

applied to hard-shell and soft elastic capsules.
 Types of tablet coating
• Three main types are in use:
1. Film coating
2. Sugar coating
3. Press coating.

• Of these, film coating is the major technique: virtually all

new coated products introduced on to the market are film
coated.

• Sugar coating is the more traditional technology and has

seen no real developments in recent years. As a proportion
of the total output of coated tablets on a global basis,
though, it is still of some economic importance.
 Reasons for coating tablets
1. Ingredients may need protection from the
environment, particularly light and moisture.

2. Many drugs have a bitter or otherwise unpleasant

taste: coating is an efficient way to mask such
tastes. Tablets that are coated are also somewhat
easier to swallow than uncoated tablets.

3. Coloured coatings also mask any batch differences

in the appearance of raw materials and hence allay
patient concern over tablets of differing
appearance.
Factors 2 and 3 aid patient compliance with dosage
schemes.
4. Coatings may be optimized with respect to colouration and
gloss to aid in their sales appeal or to reinforce a marketing
brand identification.

5. Coloured coatings aid in the rapid identification of product

by the manufacturer, the dispensing pharmacist and the
patient.

6. Coating tablets facilitates their handling on high speed

automatic filling and packaging equipment:
• Very often coating confers an added mechanical strength to
the tablet core.
• Cross contamination is also reduced in the manufacturing
plant, as 'dusting' from tablets is eliminated by coating.

7. Functional film coatings are used to impart enteric or

controlled-release properties to the coated tablet or, more
usually, to coated multiparticulates .
 FILM COATING
• This is the more modern and generally used
technology in tablet coating.
• Nearly all newly launched coated products are film coated
rather than sugar coated, for the reasons given in Table 28.1.
 Process description
• Film coating involves the deposition, usually by a spray
method, of a thin film of polymer surrounding the tablet core.

• It is possible to use conventional panning equipment, but

more usually specialized equipment is employed to take
advantage of the fast coating times and high degree of
automation possible.

• The coating liquid (solution or suspension) contains a polymer

in a suitable liquid medium together with other ingredients
such as pigments and plasticizers.

• This solution is sprayed on to a rotating, mixed tablet bed or

fluid bed. The drying conditions permit the removal of the
solvent so as to leave a thin deposition of coating material
around each tablet core.
 Coating suspension formulation
• Typically this comprises:
1. Polymer
2. Plasticizer
3. Colourants
4. Solvent.
 Ideal characteristics of a film coating
polymer
• Solubility:
1. For conventional film coating the polymer should
have good solubility in aqueous fluids to facilitate
the dissolution of the active ingredient from the
finished dosage form.

2. However, where a modified-release action is

required then a polymer system of low water
solubility or permeability will be chosen.
• Viscosity:
• In general, polymers should have a low viscosity for
a given concentration.
• This will permit the easy, trouble-free spraying of
their solutions in industrial film coating equipment.

• Permeability:
• Film coating can be used to optimize the shelf-life of
a tablet preparation, as some polymers are efficient
barriers against the permeability of water vapour or
other atmospheric gases.
• These properties vary widely between the individual
polymers.
• Mechanical properties:
• The particular polymer chosen for a film coat
formulation must be one with adequate strength to
withstand the impact and abrasion encountered in
normal handling.

• Insufficient coating strength will be demonstrated

by the development of cracks and other
imperfections in the coating.

• It should be mentioned that the polymer chosen

must also comply with the relevant regulatory and
pharmacopoeial requirements current in the
intended marketing area
 Types of polymer available
1. Cellulose derivatives
2. Methacrylate amino ester copolymers
3. Ethylcellulose and the ammonio
methacrylate copolymers
 Cellulose derivatives
• Most are substituted ethers of cellulose.

• Hydroxypropyl methylcellulose is the most widely

used of the cellulosic polymers:
1. It is soluble in aqueous media
2. forms films which are mechanically tough and
relatively easy to apply.
3. The resultant film can be clear or coloured with
permitted pigments.

• Other cellulosic derivatives used in film coating are:

1. Methylcellulose
2. Hydroxypropyl cellulose. soluble
Hydroxypropyl methylcellulose
Methacrylate amino ester copolymers
• Basically these polymers are insoluble in water
below pH 4, but in neutral or alkaline media the
films achieve solubility by swelling and increased
permeability.

• For simple formulations the disintegration of the

coating can be optimized by the incorporation of
water-soluble materials and also by starches.

• Chemically an example is the polymer

poly(butylmethacrylate) (2-dimethylaminoethyl)
methacrylate methylmethacrylate.
• For coatings designed to confer a modified release
aspect to the final dosage form, more water-
insoluble polymers are used.

• These include ethylcellulose and the

ammonio methacrylate copolymers.

• Yet another group of polymers is designed to provide

an enteric protection to the dosage form. This effect
is achieved by a pH selectivity of the polymer where
it is insoluble at the low pH environment of the
stomach yet becomes soluble as the higher pH of the
duodenum and the distal portion of the
gastrointestinal system is reached.
 Aqueous polymer dispersions
• Industrially, specialized dispersions of water
insoluble polymers such as ethylcellulose and
ammonio methacrylate copolymers for use in
aqueous media are frequently encountered in the
coating of beads and granules for use in modified
release preparations.

• The advantage of these materials is that they

permit the aqueous processing of otherwise
water-insoluble polymers, with the consequent
benefits of this method of processing.
 Plasticizers
• Plasticizers are generally added to film coating formulations to
modify the physical properties of the polymer to make it
more usable.

• One important property is their ability to decrease film

brittleness.

• It is generally accepted that the mechanism by which polymers

exert their action is for them to interpose themselves on a
molecular scale between the polymer strands.

• In doing so they permit these strands to move more freely and

allow the polymer to act in a more pliable fashion.

flexible
• Examples of plasticizers are:
1.polyols, such as polyethylene glycol 400
2.organic esters, such as diethyl phthalate
3.oils/glycerides, such as fractionated coconut oil.

• In general, only water-miscible plasticizers can

be used for aqueous-based spray systems.
 Colourants
• Any permitted colourants in a film coat formula are invariably
water-insoluble colours (pigments).

• Pigments have certain advantages over water-soluble colours:

1. they tend to be more chemically stable towards light
2. provide better opacity and covering power
3. optimize the impermeability of a given film to water vapour.

• Examples of colourants are:

1. iron oxide pigments
2. titanium dioxide
3. aluminium Lakes.
 Solvents
• After the early development of film coating in
the 1950s the polymers used were invariably
dissolved in an organic solvent.

• Modern techniques now rely on water as a

solvent because of the significant drawbacks
that readily became apparent with the use of
organic solvents.
• The disadvantages of organic solvents:
• Environmental: the venting of untreated organic solvent
vapour into the atmosphere is ecologically unacceptable, and
efficient solvent vapour removal from gaseous effluent is
expensive.

• Safety: organic solvents provide explosion, fire and toxic

hazards to plant operators.

• Financial:
1. the use of organic solvents necessitates the building of flame-
and explosion-proof facilities.
2. Ingredient cost is also comparatively high,
3. the associated costs of storage and quality control.

• Solvent residues: for a given process the amount of residual

organic solvent in the film must be investigated.
 Process details
• The vast majority of film-coated tablets are produced by a
process which involves the atomization (spraying) of the
coating solution or suspension on to a bed of tablets.

• Some examples of equipment suitable for film coating

include:
1. Accela Cota - Manesty Machines, Liverpool, UK
2. Hi-Coater - Freund Company, Japan
3. Driacoater - Driam Metallprodukt GmbH, Germany
4. HTF/150-GS, Italy
5. IDA - Dumoulin, France.
• Examples of units that function on a fluidized-
bed principle include:

1. Aeromatic-Fielder, Switzerland and UK

2. Glatt AG, Switzerland and Germany
Accela Cota
 Basic process requirements for film
coating
1. adequate means of atomizing the spray liquid for application
to the tablet cores;

2. adequate mixing and agitation of the tablet bed:

• Spray coating relies upon each core passing through the area
of spraying. This is distinct from sugar coating, where each
application is spread from tablet to tablet prior to drying;

3. sufficient heat input in the form of drying air to provide the

latent heat of evaporation of the solvent.
• This is particularly important with aqueous-based spraying;

4. good exhaust facilities to remove dust- and solvent-laden air.

 Ideal characteristics of film-coated
tablets
1. should display an even coverage of film and colour.

2. There should be no abrasion of tablet edges or

crowns.

3. Logos and break lines should be distinct and not filled

in.

4. The tablet must also be compliant with finished

product specifications and any relevant compendial
requirements.
 Coating faults
• These arise from two distinct causes:
• Processing: for example, inadequate drying
conditions will permit coating previously deposited
on the tablet surface to stick against neighbouring
tablets. When parted, this will reveal the original
core surface underneath.

• Formulation faults: film cracking or 'bridging' of

break lines are examples of this type. After taking
due account of the mechanical properties of the film,
reformulation will almost certainly be successful in
overcoming the problem
 SUGAR COATING
• Sugar coating may be considered the traditional method of
coating tablets.

• It involves the successive application of sucrose-based

solutions to tablet cores in suitable coating equipment.

• Conventional panning equipment with manual application of

syrup has been extensively used, although more specialized
equipment and automated methods are now making an
impact on the process.
 Stages involved in the production of
sugar-coated tablets
• Sugar coating is a multistage process and can
be divided into the following steps:
1. Sealing of the tablet cores
2. Subcoating
3. Smoothing
4. Colouring
5. Polishing
6. Printing.
 Sealing
• Initially the tablet cores to be sugar coated are sealed against
the entry of water by the application of a water-
impermeable polymer.

• Shellac has traditionally been used for this purpose and is

indeed still used a great deal today, although more reliable
materials, such as cellulose acetate phthalate and polyvinyl
acetate phthalate, also find favour.
 Subcoating

• To attain the typically rounded profile of a sugar

coated tablet the sealed tablet core must be built up
to gain the desired profile.

• This process of subcoating is usually performed by

adding bulking agents such as calcium carbonate or
talc to the applied sucrose solutions.

• A gum such as acacia is also added to the applied

suspension.
 Smoothing
• After the correct profile has been obtained the subcoated
tablets will almost certainly have a rough surface, which will
have to be made smooth before the next stage can be
commenced.
• This is accomplished by the application of a few coats of
sucrose syrup.

Colouring
• Nearly all sugar-coated tablets are coloured, as aesthetic
appearance is usually considered to be of great importance
with this dosage form.
• The pigments used are those permitted by the national
legislation of the country where the products are to be
marketed.
 Polishing
• After the colour-coating stage the tablets will require a
separate polishing stage for them to acquire an acceptable
appearance. Several methods can be used, but commonly
beeswax and carnauba wax are used in the process.

Printing
• To facilitate identification sugar-coated tablets are usually
printed with a manufacturer's logo or code.
• The printing process used is an offset gravure in conjunction
with special edible inks,
safe to eat
although the inkjet process is starting to make an impact.
 Process details
• Typically tablets are sugar coated by a panning
technique.

• The simplest form would be a traditional

sugar-coating pan with a supply of drying air
(preferably of variable temperature and
thermostatically controlled) and
a fan-assisted extract to remove dust- and
moisture-laden air.
• Methods of applying the coating syrup include
1. manually using a ladle,
2. automatic control.
• In modern equipment some form of automatic
control is available for the application of coating
syrups.

• In general, the equipment listed under film

coating can, with suitable modification, be used
for sugar-coating techniques.
 Ideal characteristics of sugar-coated
tablets
1. First the tablets must comply with finished product
specifications and any appropriate compendial
requirements.

2. Sugar-coated tablets should ideally be of a perfectly

smooth rounded contour with even colour
coverage.
• Most manufacturers take advantage of the
aesthetic appeal of a sugar-coated tablet and polish
to a high gloss.

3. Any printing should be distinct, with no smudging

or broken print.
 Coating faults

• These are usually associated with process

defects, such as splitting of the coat on
storage, caused by inadequate drying during
the coating application.
 PRESS COATING
• The technology of press coating differs radically from the
previously described film- and sugarcoating techniques.

• Press coating involves the compaction of granular material

around an already preformed core using compressing
equipment similar to that used for the core itself, e.g.
Manesty Drycota.

• Today press coating is used mainly to separate chemically

incompatible materials, one or more being placed in the core
and the other(s) in the coating layer.

Compaction of granular
material around an already
preformed core.
• However, there is still an interface of contact left
between the two layers.

• In cases where even this is important then the

process of press coating can be taken one stage
further.

• It is possible to apply two press coatings to a tablet

core using suitable equipment, e.g. Manesty Bicota.

• This equipment produces press-coated tablets with

perfect separation between active core and coating,
as the two can be separated by an inert middle layer.
• The formulation and processing of the coating layer
requires some care.

• Large or irregularly sized agglomerates of granules

will cause the core to tilt in the second die used for
compression of the coating.
• Thus there is the possibility of an incomplete
coating, with the core being visible at the tablet
surface.

• The disadvantages of the process arise from the

relative complexities of the mechanism used in the
compressing equipment.
 FUNCTIONAL COATINGS
• All the coatings described above have been
designed as a taste mask, as an identification
aid, or indeed for many of the reasons
previously discussed for coating tablets.

• There are, however, tablet coatings that

perform a pharmaceutical function, such as
conferring controlled or enteric release on the
dosage form.
 Controlled-release coatings

• Film coating provides an extremely effective way of

conferring a controlled-release aspect to a tablet or,
more usually, a multiparticulate system.

• After coating these particles are filled into hard gelatin

shells, or occasionally compressed directly into tablets
by a process which permits minimal rupture of the
applied film.

• The coatings involved use polymers with restricted

water solubility or permeability, and include
ethylcellulose and modified acrylate derivatives.
• Multiparticulates, commonly referred to as 'pellets'
or 'beads', find favour over conventional non-
disintegrating tablets for controlled release use,
owing to a number of factors:

1. Their small size (typically 0.7-2.00 mm) allows them

to:
• pass through the constricted pyloric sphincter and
• distribute themselves along the gastrointestinal
tract.
• This tends to overcome the disadvantage that whole
tablets have of a rather irregular passage through
the gastrointestinal tract and consequent irregular
absorption
2. Whole, non-disintegrating tablets can be liable to
lodge in restrictions within the gastrointestinal tract,
and this can lead to ulcerative damage to the gastric
mucosa as the drug solution is leached out from the
tablet.
• Because of their small size, this is not a problem with
multiparticulates.

3. Should an individual bead or pellet fail and release all

of its contents at once the patient would not be
exposed to any undue risk.
•This is certainly not the case if a non-disintegrating
tablet failed, when the consequences would potentially
be serious.
 Types of multiparticulate
• Drug crystals
• Irregular granules
• Spheronized granulates
• Drug-loaded Non-pareils
• Mini tablets
 Drug crystals
Drug crystals, as long as they are of the
appropriate size and shape (elongated or acicular crystals should
be avoided), can be directly coated with a modified release film
coating.

Irregular granules
Granulates, such as those regularly used to
prepare tablets, can be film coated but
variation in particle size distribution ( from batch to batch), as
well as the angular nature of such particles, can make it difficult
to achieve uniform coating thickness around each particle.
 Spheronized granulates
• Spheroidal particles simply the coating process.
• These are produced in modified granulating
equipment, with the drug granulation extruded
through a mesh or other device under pressure
to form small granulates which are
subsequently spheronized
 Drug-loaded Non-pareils

• Another process or producing spheroidal particles involves

the application of drug to the surface of placebo pellets,
often called nonpareils. spherical particles about 1
mm in diameter consisting primarily of sucrose and
starch,may also be prepared using microcrystalline cellulose.
• The spheres which are coated with the drug plus an adhesive
yet water soluble polymer.
• After their formation and any necessary intermediate steps
such as drying.
• they may be coated with the controlled-release coating.
• Application of the drug uses either:
1. A powder-dosing technique involving
alternate dosing of powder (containing the drug substance)
and binder liquid onto the surface of the nonpareils until
the required dose of drug has been achieved.

2. Spray application of drug, either suspended or dissolved in a

suitable solvent (usually water) containing also a polymer
binder (such as hydroxypropyl methylcellulose or polyvinyl
pyrrolidone) onto the surface of the nonpareils.

Nano- carrier for vaccines

 Mini tablets

• Many of the other types of multiparticulates described so far

suffer from two potential batchwise drawbacks, namely:
1. variation in particle size distribution
2. variation in particle shape and surface roughness.

• Such variability can result in variable coating thickness and thus

product performance.

This problem can be overcome by using mini compressed

tablets (typically in the size range of 1–2 mm) produced using a
modification of traditional tableting processes.
 Mechanisms of drug release from
multiparticulates
• Discussed earlier.
• Diffusion
• Dissolution
• Erosion
• Osmosis
 Enteric coating
This technique is used to protect the
tablet core from disintegration in the acid
environment of the stomach for one or more of the
following reasons:

1.Prevention of acid attack on active constituents

unstable at low pH;
2.To protect the stomach from the irritant effect of
certain drugs;
3.To facilitate absorption of a drug that is
preferentially absorbed distal to the stomach.
• The following polymers are among those
commonly used for the purposes of enteric
coating:

1.Cellulose acetate phthalate

2.Polyvinyl acetate phthalate
3.Suitable acrylic derivatives.
• Because they possess free carboxylic acid groups on
the polymer backbone, they exhibit a differential pH
solubility profile.

• They are almost insoluble in aqueous media at low pH,

but as the pH rises they experience a sharp, well
denned increase in solubility at a specific pH, e.g. pH
5.2 for cellulose acetate phthalate.

• Enteric coating is possible using both sugar- and film-

coating techniques.
 Enteric film coating
• The enteric polymers listed are capable of forming a direct film
in a film-coating process.
• Sufficient weight of enteric polymer must be used to ensure
an efficient enteric effect.
• This is normally two or three times that required for a simple
film coating.

Enteric sugar coating

• The sealing coat is modified to comprise one of the enteric
polymers in sufficient quantity to pass the enteric test for
disintegration.
• The subcoating and subsequent coating steps are then as for
conventional sugar coating.
 STANDARDS FOR COATED TABLETS
• The European Pharmacopoeia has similar requirements for
coated and uncoated tablets, the differences being:

1. Film-coated tablets must comply with the uniformity of mass

test unless otherwise justified and authorized.

2. Film-coated tablets comply with the disintegration test for

uncoated tablets except that the apparatus is operated for 30
minutes. The requirement for coated tablets other than film
coated is modified to include a 60-minute operating time.
Furthermore, the test may be repeated using 0.1 N HC1 in the
event that any tablets fail to disintegrate in the presence of
water.