Вы находитесь на странице: 1из 105

Coating materials used

in pharmaceutical
formulations
Click to start tutorial

By Mahya Akbarzadeh

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 as coating materials

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

Convenient, clean and safe way

Disadvantages
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

Can mask unpleasant taste

Drug delivery market

Oral drug delivery system


Drug Delivery Market
$75.3 billion in 2004

Transdermal
Pulmonary

11%
9%

Oral

32%

Other

13%
8%
27%

Injectable and
implantable
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:

STOMACH:

SMALL INTESTINE:

LARGE INTESTINE OR COLON: Final part of the GI

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.

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.

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.

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
A
S
T
E
D

STOMACH

Gastric fluid in the stomach is highly acidic, ranging between


pH1-3.5 in the fasted state.
In the fed state the pH rises in the range of pH3-7
depending on the composition of the meal.

F
E
D

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 gastrointestinal tract
The 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:


1.
Oesophagus
2.
Stomach
3.
Small intestine
4.
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.
2.
3.
4.
5.
6.

Seal tablet core


Sub coating
Smoothing
Colouring
Polishing
Printing

Examples of sugar coated tablets

Multistage process
1.

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.

2.

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

3.

Smoothing process

-remove rough layers formed in step 2 with the

application of sucrose syrup.


4.

Colouring

- for aesthetic purposes often titanium based pigments are

included.

5.

Polishing - effectively polished to give characteristic shine, commonly using


beeswax, carnauba wax.

6.

Printing -indelible ink for characterisation.

Example of sugar coated tablets


Brufen POM

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

1.
2.
3.
4.

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
coating pan
Easy training operation
Considerable
training
operation
Single stage process
required
Easily adaptable for controlled release
Multistage process
allows for functional coatings.
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
STOMACH
LOW

pH
HIGH
SMALL INTESTINE

The polymers used for enteric coatings remain unionise


at low pH, and therefore remain insoluble. As the pH
increases in the gastrointestinal tract the acidic functional
groups are capable of ionisation, and the polymer swells
or becomes soluble in the intestinal fluid.
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
it can exert its pharmacologic effects.

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
Marcoat 125

Enteric Coatings
Taste/Odor Masking

Cellulose acetate

Aquacoat CPD
Sepifilm LP
Klucel
Aquacoat ECD
Metolose

Polyvinylacetate phthalate

Sureteric

Methacrylate

Eudragit

Enteric Coatings
Taste masking
Sustained release coating
Sub coat moisture and barrier
sealant pellet coating
Enteric Coatings

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 copolymers 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


application?

different amounts for

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
CH 3(H)
C

CH3
C

COO-ALKYL

Changing the R group gives rise to polymers with different physiochemical


properties.

Possible R groups
-COOCH3 or COOC4H9

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

CH 3(H)
C

CH3
C

COO-ALKYL

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!
Try again

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!
Well done

Incorrect!
Try again

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!
Try again

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!
Try again

9. The trade name for methacrylate polymer is ...

Sureteric

Eudragit

EmCoat 120 N

Correct!
Well done

Incorrect!
Try again

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

Вам также может понравиться