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in pharmaceutical
formulations
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By Mahya Akbarzadeh
AIMS
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?
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
Coatings
Functional coatings
Polymers
Eudragit Polymers
Polymer dissolution
Polymer Quantities
Tablets
Capsules
Lozenges
Pastilles
Powders
Granules
Advantages
Disadvantages
Difficult to swallow
Difficult to dilute
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.
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:
tract which spans from the ileocaecal junction to the anus. It makes up 1.5
meters of the 6 meters of the GI tract.
Gastrointestinal pH
Enzymatic status
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
F
E
D
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
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 food
Dietary intake
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.
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.
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
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.
Multistage process
1.
2.
Sub coating -by adding bulking agents such as calcium carbonate or talc in
combination with sucrose solution.
3.
Smoothing process
Colouring
included.
5.
6.
Premarin POM
Colofac P
Mebeverine hydrochloride
100mg Round, white, sugar
coated
Kalms GSL
Film coating
1.
2.
3.
4.
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.
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.
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
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
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.
pH
HIGH
SMALL INTESTINE
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
Shellac
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
pH
Other excipients
Ionic state
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
Other excipients
CH3
C
COO-ALKYL
Possible R groups
-COOCH3 or COOC4H9
-COO-CH2-CH2N+(CH3)3 3CL-
CH 3(H)
C
CH3
C
COO-ALKYL
-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)
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.
These are copolymers derived from esters of acrylic and methacrylic acid in, which
properties are determined by the R group.
They contain COOH as a functional group. They dissolve at ranges from pH 5.5 to
pH 7.
Quiz
1.
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Sureteric
Eudragit
EmCoat 120 N
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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