Coating materials

used
in pharmaceutical
formulations
By Mahya Akbarzadeh
Click to start tutorial
AIMS
Aims and objectives
After finishing the package what should you understand?

 You should understand the term biomaterials and their role in pharmaceutics.
 You should be able to discuss the rationale for coating solid dosage form.
 You should know aims of functional coatings.

OBJECTIVES
After completing the package what should you be able do?

 Appreciate the importance of coating with respect to oral bioavailability .

 Describe the different coating processes: sugar, film and press.
 State the different types of polymers, which can be used for enteric coating.

PREREQUISITES
What do you need to do before starting the activity?
 Basic pharmaceutics
 Human biochemistry
 MAIN MENU
 Oral drug delivery system
 Coatings
 Polymers used in coating processes
 Quiz
 Useful links
 Oral drug delivery system

 Oral drug delivery system

 Anatomy and physiology of the gastrointestinal tract

 Physiological factors affecting bioavailability

 Coatings
 What is the rationale for coating a solid dosage form?

 Main coating processes

 Functional coatings
 Polymers

 Summary of Polymers used in pharmaceutical formulations

 Eudragit® Polymers

 Polymer dissolution

 Polymer Quantities
 Oral drug delivery
system
The oral route constitutes as the most familiar means of administering drugs,
mainly because it is the most natural and convenient for the patient.

Solid oral dosage forms include;

 Tablets

 Capsules

 Lozenges

 Pastilles

 Powders

 Granules
 Oral drug delivery system
Tablets are the most commonly prescribed dosage form, below summarises
the advantages and disadvantages of tablets.

Advantages Disadvantages
 Convenient, clean and safe way  Difficult to swallow
 Physical and chemical stability –long
shelf life  Difficult to dilute

 Accurate dose of drug  Difficult for liquid drugs

 Economic- mass production

 Can be formulated as controlled

release
Drug delivery market
 Can mask unpleasant taste
 Oral drug delivery system
Oral
Drug Delivery Market
$75.3 billion in 2004 Transdermal

11% Pulmonary
9% 32%
Other
13%
Injectable and
8% implantable
27% Nasal

The oral drug delivery market continues to dominate the

industry, but alternate routes of delivery such as pulmonary and
transdermal are being developed to provide patients with less
invasive routes of delivery.
 Anatomy and physiology of the
gastrointestinal tract
The gastrointestinal tract is complex system and below
outlines the key structures involved oral drug absorption.
 Anatomy and physiology of the
gastrointestinal tract
The oral route is main route in which pharmaceuticals are administered,
therefore it is important to be aware of how these materials behave during
their passage through the GI tract. Drugs taken orally have a much lower
bioavailability compared to drugs administered intravenously, which have a
bioavailability of 100 %.

Facts
 GI tact is a muscular tract approximately 6 meters in length with varying
diameters.
 It starts at the mouth and ends at the anus and consists of FOUR main
anatomical areas.
1. OESOPHAGUS
2. STOMACH
3. SMALL INTESTINE
4. LARGE INTESTINE OR COLON
 Bioavailability
The proportion of drug that reaches the
target organs and tissues, which is
expressed as a % of the dose
administered.
 OESOPHAGUS: The mouth is the main entry, it links the oral
cavity to the stomach. Composed of a thick muscular layer, 250 mm long and
20mm in diameter.

 STOMACH: It is situated between the lower oesophagus and the

small intestine. It is the most dilated part of the GI tract. It has a capacity of 1.5L
although in fasted state it usually contains no more than 50ml of fluid.

 SMALL INTESTINE: It is longest and most convoluted part

of the GI tract, 4-5 meters in length. It begins from the pyloric sphincter of the
stomach to the ileocaecal junction where it joins the large intestine.

 LARGE INTESTINE OR COLON: Final part of

the GI tract which spans from the ileocaecal junction to the anus. It makes up 1.5
meters of the 6 meters of the GI tract.
 Physiological considerations that
affect oral bioavailability
 The transit of pharmaceuticals in the gastrointestinal tract

 Gastrointestinal pH

 Enzymatic status

 Presence of foods and liquids in the gastrointestinal tract

 Gastrointestinal pH
The pH varies considerably along the length of the
gastrointestinal tract.
Different regions along the tract will exhibit different pH values.

F STOMACH
A Gastric fluid in the stomach is highly acidic, ranging
between pH1-3.5 in the fasted state. F
S
E
T
In the fed state the pH rises in the range of pH3-7 D
E
D depending on the composition of the meal.

The variability in pH of the stomach is an important consideration

when taking a medicament with respect to the drugs chemical
stability or achieving drug dissolution or absorption.
 Gastrointestinal pH
SMALL INTESTINE
Intestinal pH is much higher than gastric fluid due to neutralisation with
bicarbonate ions secreted into the small intestine by the pancreas. The pH values
increase along the small intestine e.g. from ph ~6.1 in duodenum to ~7.8 in the
ileum.

LARGE INTESTINE
The pH of the caecum is around 6-6.5, which increases towards the distal parts of
the colon to pH 7-7.5.
 Enzymatic status
 Luminal enzymes of the small intestine
Pepsin is the primary enzyme found in gastric fluid. Other enzymes such as
lipases, amylases and peptides are secreted into the small intestine via the
pancreas in response to ingestion of food. Pepsins and proteases are
responsible for the breakdown of protein and peptide drugs in the lumen.
Drugs which resemble nutrients such as fatty acids and nucleotides are
susceptible to enzymatic attack.
 Colon
Presence of bacterial enzymes in the colonic region of the gastrointestinal
tract, which digest material not yet digested in the small intestine.
Presence of foods and liquids in the
gastrointestinal tract
The rate and extent of drug absorption in the gastrointestinal tract
depends on the following factors:

 Presence of food

 Dietary intake

 Delayed gastric emptying

 Increased viscosity of the gastrointestinal contents

 Stimulation of gastrointestinal secretion

 Presence of food
Food tends to increase the pH of the stomach by
acting as a buffer. Increase in pH is likely to decrease
the rate of dissolution and thus absorption of a
weakly basic drug but increase that of a weakly acidic
drug.
 Dissolution
Release of a drug from solid dosage form into
a bioavailable form .
 Dietary intake
Certain foods such as milk, iron preparations
or indigestion remedies which contain
magnesium or aluminium can form insoluble
complexes with drugs. Therefore, reducing the
bioavailability of the drug to exert its
therapeutic effect.
Delayed gastric emptying

Foods which are high in fat tend to reduce gastric

emptying, therefore delaying the onset of action of
various drugs.

In addition, the presence of fat stimulates the release

of bile salts which are surface active agents which
enhance the absorption of poorly absorbed drugs.
However, they have been found to form insoluble and
non-absorbable complexes with certain drugs.
Increased viscosity of the
gastrointestinal contents

The presence of food increases the viscosity of

gastrointestinal content which may result in a
reduction in rate of drug dissolution
 Stimulation of
gastrointestinal secretion
Gastrointestinal secretions in response to food
such as pepsin may result in enzymatic
degradation of drugs which are susceptible
therefore reducing their bioavailability.
 The transit of
pharmaceuticals in the
Thegastrointestinal tract
transit time simply refers to the contact time of the drug within any part of the
GI tract. Various factors affect transit time, which include;

 Age and gender of patient

 Presence of disease
 Posture
 Emotional state
 Dietary intake
 Size and density of dosage form

Location and transit time within the GI tract:

11. Oesophagus
12. Stomach
13. Small intestine
14. Large intestine or colon
The transit of pharmaceuticals in the
gastrointestinal tract
Once a drug is placed in the mouth it is moved down the
oesophagus by the swallowing reflex. The transit time of the
dosage form in the oesophagus is rapid usually 10-14 seconds.

The transit time in the stomach is highly variable and depends

on the dosage form and the fed or fasted state of the stomach.

The transit time is relatively constant, at around 3 hours. This

contrasts with the stomach as it does not discriminate between
different dosage forms or between fed or fasted state. It the main site
for absorption for most drugs. Hence, an important parameter for
drug targeting.

The transit time is long and variable and depends on

the following; type of dosage form, diet, eating pattern
and disease state.
 What is the rationale for
coating a solid dosage form?
Coating of a solid dosage form is often designed to perform a specific function. For
example; protection against moisture, taste masking pH or time controlled release.

Tablets can be easily coated and a variety of products are available on the market.
Generally, the coating process gives rise to;
 Increased bioavailability
 Improved patient acceptance
 Formulation stability

The rationale for coating pharmaceutical dosage form such as a tablet can be
categorised into three main headings:

 Therapy
 Technology
 Marketing
 What is the rationale for
coating a solid dosage form?
Therapy

 To minimise irritation of the oesophagus and stomach.

 Minimise inactivation in the stomach.

 Improve drug effectiveness.

 Improve patient compliance e.g. easier to swallow, masks unpleasant taste.

 What is the rationale for
coating a solid dosage form?
Technology

 Minimise dust formation and contamination with respect to tablets.

 Masks batch differences in the appearance of raw materials.

 Facilitates their handling on high speed automated filling and packaging

equipment.

 Improves drug stability e.g. Protection of active ingredient from

environment such as sunlight, moisture.
 What is the rationale for
coating a solid dosage form?
Marketing

 Aid sales appeal as improved appearance and acceptability with respect to

gloss and colouration.

 Mask unpleasant taste.

 Improve product identity.

Main coating processes

1.Film coating

2. Sugar coating

3. Press coating
 Sugar

coating
Traditionally sugar coatings formed the bulk of coated tablets but today film coatings
are the more modern technology in tablet coating.
 Description of tablets: Smooth, rounded and polished to a high gloss.
 Process: Multistage process involving 6 separate operations.
1. Seal tablet core
2. Sub coating
3. Smoothing
4. Colouring
5. Polishing
6. Printing

Examples of sugar coated tablets

 Multistage process
 Sealing tablet core- application of a water impermeable polymer such as
Shellac, cellulose acetate phthalate and polyvinyl acetate phthalate, which
protects the core from moisture, increasing its shelf life.

 Sub coating -by adding bulking agents such as calcium carbonate or talc in
combination with sucrose solution.

 Smoothing process -remove rough layers formed in step 2 with the

application of sucrose syrup.

 Colouring - for aesthetic purposes often titanium based pigments are

included.

 Polishing - effectively polished to give characteristic shine, commonly using

beeswax, carnauba wax.

 Printing -indelible ink for characterisation.

 Example of sugar coated
Brufen® POM tablets
 Available in 200mg and 400mg
strength

Premarin® POM
 Conjugated oestrogens 625mcg
(maroon) and 1.25mcg (yellow)

Colofac ® P
 Mebeverine hydrochloride
100mg Round, white, sugar
coated

Kalms ® GSL
 45mg Hops powder,90mg
Gentian powdered extract, and
135mg Valerian powdered
extract
Simplified representation of
sugar coating process
 Film coating
 Modern approach to coating tablets, capsules, or pellets by surrounding them with
a thin layer of polymeric material.
 Description of tablets: Shape dictated by contour of original core.

 Process: Single stage process, which involves spraying a coating solution

containing the following;
 Polymer
 Solvent
 Plasticizer
 Colourant

The solution is sprayed onto a rotating tablet bed followed by drying, which
facilitates the removal of the solvent leaving behind the deposition of thin film of
coating materials around each tablet.
 Film coating

Advantages
Produce tablets in a single step process in relatively short
period of time. Process enables functional coatings to be
incorporated into the dosage form.

Disadvantages
There are environmental and safety implications of using
organic solvents as well as their financial expense.

Why film coating is favoured over sugar coating?

 Accela Cota

The vast majority of film coated tablets are produced by a process which
involves spraying of the coating material on to a bed of tablets. Accela Cota is
one example of equipment used for film coating.
 Why is film coating favoured
over sugar coating ?
Film coating Sugar coating
Tablet appearance Tablet appearance
 Retains shape of original core  Rounded with high degree of polish
 Small weight increase of 2-3% due to  Larger weight increase 30-50% due to
coating material coating material
 logo or ‘break lines’ possible  Logo or ‘break lines’ are possible
Process Process
 Can be automated e.g. Accela Cota  Difficult to automated e.g. traditional
 Easy training operation coating pan
 Single stage process  Considerable training operation
 Easily adaptable for controlled required
release allows for functional coatings.  Multistage process
 Not able to be used for controlled
release apart from enteric coating.
 Polymer used in film
coating
Examples;
 Cellulose derivatives
 Methacrylate amino ester copolymers.
 Plasticizer used in film
coating
Examples;
 Polyols - Polyethylene glycol 400
 Organic esters - diethyl phthalate
 Oils/glycerides - fractional coconut

oil
 Colourants used in film
coating
Examples;
 Iron oxide pigments
 Titanium dioxide
 Aluminium lakes.

Water insoluble pigments are more favourable than water

soluble colours for the following reasons;
 Better chemically stability in light
 Optimised impermeability to water vapour
 Better opacity
 Better covering ability
 Environmental
Venting of untreated organic solvent vapour
into the atmosphere is ecologically
unacceptable but removal of gaseous effluent
is expensive.
 Safety
Organic solvents are a safety hazard, such that they are:

Toxic

Explosive

Fire hazard
 Financial
The hazards associated with organic solvents
necessitates the need for building flame- and
explosive- proof facilities. In addition, the cost
of their storage and ingredients are relatively
expensive.
 Solvent residues
For a given process the amount of residual
organic solvent in the film must be
investigated. Thus, stringent regulatory
controls exist.
 Solvents
Traditionally, organic solvents had been used to
dissolve the polymer but modern techniques rely on
water because of significant drawbacks. Below lists
some of the problems associated with organic
solvents.
 Environmental
 Safety
 Financial
 Solvent residues
 Press coating
Press coating process involves compaction of coating material around a
preformed core. The technique differs from sugar and film coating process.

Advantages
This coating process enables incompatible materials to be formulated
together, such that one chemical or more is placed in the core and the other
(s) in the coating material.

Disadvantages
Formulation and processing of the coating layer requires some care and
relative complexities of the mechanism used in the compressing equipment.
 Functional coatings
Functional coatings are coatings, which perform a
pharmaceutical function.
These include;

 Enteric coating
- The pH status of enteric coated polymers in the stomach
- The ideal properties of enteric coated material

 Controlled release coating

 Enteric coating
The technique involved in enteric coating is protection of the tablet core from
disintegration in the acidic environment of the stomach by employing pH sensitive
polymer, which swell or solubilize in response to an increase in pH to release the
drug.

Aims of Enteric protection:

 To mask taste or odour
 Protection of active ingredients, from the acidic environment of the stomach.
 Protection from local irritation of the stomach mucosa.
 Release of active ingredient in specific target area within gastrointestinal tract.

Examples of enteric coated OTC products

Examples of enteric coated OTC
products

 Enteric coated aspirin E.g. Micropirin®

75mg EC tablets

 Enteric coated peppermint oil E.g.

Colpermin®
 The pH status of enteric coated
polymers in the stomach
The polymers used for enteric coatings remain unionise
STOMACH at low pH, and therefore remain insoluble. As the pH
increases in the gastrointestinal tract the acidic functional
LOW groups are capable of ionisation, and the polymer swells
or becomes soluble in the intestinal fluid.

pH Thus, an enteric polymeric film coating allows the coated

solid to pass intact through the stomach to the small
intestine, where the drug is then released for absorption
through the intestinal mucosa into the human body where
HIGH it can exert its pharmacologic effects.

SMALL
INTESTINE
The ideal properties of enteric
coated material?
 Permeable to intestinal fluid
 Compatibility with coating solution and drug
 Formation of continuous film
 Nontoxic
 Cheap and ease of application
 Ability to be readily printed
 Resistance to gastric fluids
 Summary of Polymers used in
pharmaceutical formulations as coating
materials.
Polymer Trade name Application
Shellac EmCoat 120 N  Enteric Coatings
Marcoat 125  Taste/Odor Masking

Cellulose acetate Aquacoat CPD®  Enteric Coatings

Sepifilm™ LP  Taste masking

Klucel®  Sustained release coating

Aquacoat® ECD  Sub coat moisture and barrier

Metolose® sealant pellet coating

Polyvinylacetate phthalate Sureteric®  Enteric Coatings

Methacrylate Eudragit®  Enteric Coatings

 Sustained Release Coatings
 Taste Masking
 Moisture protection
 Rapidly disintegrating Films
 Shellac
 Material of natural origin- purified resinous secretion of the
insect Laccifer lacca.

 Oldest known material used for enteric coatings.

 Suited for drug targeting in the distal small intestine as soluble

at pH 7.0

 Its use is now less popular in commercial pharmaceutical

applications for enteric coatings. Due to poor batch to batch
reproducibility, which is a crucial requirement.
Shellac
Cellulose acetate phthalate
(CAP)
 Chemical name: Cellulose acetate phthalate
 Trade name: CAP, Aquateric
 Application form: organic or aqueous
dispersion
 Functional groups: acetyl, phthalyl
 Soluble above pH: 6
 Additional remarks: sensitive to hydrolysis,
5-30% plasticizer required.
Polyvinyl acetate phthalate
(PVAP)
 Chemical name: polyvinyl acetate phthalate#
 Trade name: Opadry enteric (aqueous),
Coloron
 Application form: organic solution, aqueous
dispersion.
 Functional groups: acetyl, phthalate,
vinylacetat :crotonic acid ratio 90:10.
 Soluble above pH: 5
 Additional remarks: Plasticizer is required.
 Acrylic polymers
 Chemical name: Methacrylic
 Trade name: Eudragit®
 Application form: organic solution or
aqueous dispersion.
 Functional groups: methyacrylic acid
 Soluble above pH: 5 * depends on co-
polymers used.
 Polymer dissolution
Factors affecting the release of a drug from a
polymer:
 Thickness of the coating material

 pH

 Other excipients

 Ionic state
Thickness of a coating
material
 How much polymer is required for enteric protection?
To achieve enteric protection of the core 3-4 mg/cm2 of the polymer is required to
be applied to the dosage form.
 Do different polymers require different amounts for
application?
Methacrylic acid copolymers require a lower amount of polymer compared to
cellulose derivatives which usually require higher amounts of polymer to achieve
the same core protection as the former.
 What effect does increasing polymer layers have on
dissolution?
The more polymer layers that are applied the greater the rate of dissolution of the
drug.
 pH
Dissolution of polymers intended for enteric
targeting is dependent upon the dissolution
medium. This is influenced by the composition
of the polymer, the monomers, or the type and
degree of substitution.
 Ionic state
 The rate of polymer dissolution is dependent
upon the type of ions present in the dissolution
medium.

 It was shown that sodium chloride prevented

dissolution of some polymers.
 Other excipients
 Influence the dissolution of polymer.

 Plasticizers may decrease or increase

dissolution rate, depending on the nature of the
plasticizer, whether it is lipophilic or
hydrophilic.
General structure of Eudragit®
Polymers

CH3(H) CH3
C C C C

COO-ALKYL R

Changing the R group gives rise to polymers with different physiochemical

properties.
 Possible R groups
-COOCH3 or COOC4H9 -COO-CH2-CH2N+(CH3)3 3CL-

CH3(H) CH3
C C C C

COO-ALKYL R
General structure of Eudragit ®
polymers

-COOH -COOH-CH2-CH2N(CH3)2
 FUNCTIONAL GROUP

 METHACRYLIC COPOLYMER
 E.g. anionic

-COOH

Application:
 Gastro resistance
 Delivery to the colon
 FUNCTIONAL GROUP

Aminoalkyl methacrylate copolymer

E.g.
-COOH-CH2-CH2N(CH3)2

Application:
 Taste, odour and moisture protection.
Dissolves in the stomach.
 FUNCTIONAL GROUP

 Methacrylate copolymer
 E.g. neutral

-COOCH3 or COOC4H9

Applications:
 Delayed and sustained release (insoluble)
 Delayed release: The drug is not release
immediately after administration but at a later
time.

 Sustained release: An initial release of the

drug soon after administration, followed by
gradual release over an extended period.
 FUNCTIONAL GROUP

 Aminoalkyl methacrylate copolymer

 E.g.

-COO-CH2-CH2N+(CH3)3 3CL-

Application
 Delayed and sustained release
 Polymer Quantities
Depending on the desired function of a coating, the following
values are figures for the amount of polymer required :

Enteric coatings:
4 – 6 mg for round tablets
5 – 10 mg for oblong-shaped tablets
5 – 20 mg for gelatin or HPMC capsules

Taste-masking coatings:
1 – 2 mg for round tablet
1 – 4 mg for oblong-shaped tablets

Moisture protection:
1 – 6 mg for round tablets
2 – 10 mg for oblong-shaped tablets
5 – 10 mg for gelatin or HPMC capsules
 Eudragit® Polymers
 Eudragit® is the trade name for the class of polymers known as the methacrylates.

 Mostly commonly used polymer for enteric coating.

Advantages:
 Pharmacologically inactive
 Excreted unchanged

 These are copolymers derived from esters of acrylic and methacrylic acid in, which
properties are determined by the R group.

 Different grades of polymers are obtained by mixing monomers in different ratios.

ACID –NEUTRAL- ALKALINE

 They contain –COOH as a functional group. They dissolve at ranges from pH 5.5 to
pH 7.

General structure of Eudragit®

 Quiz
1. Biomaterials only include synthetic solid
materials?
 True
 False
Correct!
Well done
Incorrect!
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2. Which one of the following is NOT a type of
biomaterial?
 Active material
 Inert material
 Potent material
 Biodegradable
Correct!
Well done
Incorrect!
Try again
3. Drugs taken orally have a much higher
bioavailability compared to drugs administered
intravenously?
 True
 False
Correct!
Well done
Incorrect!
Try again
4. Gastric fluid in the stomach has a pH ranging
between 3-7 in the fed state.
 True
 False
Correct!
Well done
Incorrect!
Try again
5. Film coating is a multistage process giving
rise to the production of smooth, rounded
tablets.
 True
 False
Correct!
Well done
Incorrect!
Try again
6.Weight increase due to coating material is
minimal for Sugar coated tablets.
 True
 False
Correct!
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Incorrect!
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7. Which one of the following is NOT an ideal
property of coating material used in enteric
protection?
 Resistance to intestinal fluid
 Compatibility with coating solution and drug
 Formation of continuous film
Correct!
Well done
Incorrect!
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8. The polymers used for enteric coatings ionises
as the pH increases, and therefore becomes
soluble in the intestinal fluid.
 True
 False
Correct!
Well done
Incorrect!
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9. The trade name for methacrylate polymer is ...
 Sureteric®
 Eudragit®
 EmCoat 120 N
Correct!
Well done
Incorrect!
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Q10. The amount of polymer required for enteric
protection is less than that need for moisture
protection?
 True
 False
Correct!
Well done
Incorrect!
Try again
 END OF QUIZ
Thank-you for taking time to
look through this package.
 Useful links
Listed below are some useful links providing further
information
 Pharmpedia: tablet coating
 Dipharmatech pharmaceuticals: technical articles
 An overview of current oral modified release technologies
 Degussa for pharmaceuticals