Transcript 322 PHT Tabletäåáå

Nahla Barakat, PhD
King Saud University
Dept. of Pharmaceutics
1431/1432
Tablets
Introduction
• Tablets are oral solid unit dosage form of medicaments with or without
suitable diluents and prepared either by molding or compression. They are
solid, flat or biconvex disc in shape.
•They vary greatly in shape, size and weight which depend upon amount of
medicament used and mode of administration.
•They also vary in hardness, thickness, disintegration and dissolution
characteristics and in other aspects depending upon their intended use and
method of manufacture
•They are used for local & systemic effect.
• Usually used for oral administration
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Tablets are popular due to:
1.
A convenient and safe way of drug administration.
2.
Compared to liquid dosage form they are more physically &
chemically stable.
3. Enables more accurate dosing , easy to use, handle by the patient
4. Can be prepared in different ways according to their use.
5. Tablets are provides a sealed covering which protects the tablets from
atmospheric conditions like air, moisture and light etc.
6. The manufacturing cost of tablets is low as compared to other dosage
form .
7. The unpleasant taste and odor of medicament(s) can be easily masked by
sugar.
8.Tablets provide administration of even minute dose of drug in an accurate
amount.
9. Tablets are formulated as a special release of products such as enteric or
delayed release products.
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Disadvantages of tablet:
1. It’s not suitable for poorly water-soluble or poorly
absorbable drugs, less bioavailability.
2. Enhances local irritant effect of some drugs or cause harm
to the gastrointestinal mucosa.
3.Some drugs resist compression into dense compacts.
4. Hygroscopic drugs are not suitable candidate for compressed
tablets.
5. Drugs having bitter taste and unpleasant odor requires special
treatment like coating or encapsulation which may increase their
production cost.
6. Drugs that are sensitive to oxygen or may also require special
coating.
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General properties of Tablet dosage forms:
1.A tablet should have elegant product identity while
free of defects like chips, cracks, discoloration, and
contamination.
2.Should have sufficient strength to withstand
mechanical shock during its production packaging,
shipping and dispensing.
3.Should have the chemical and physical stability to
maintain its physical attributes over time
4.The tablet must be able to release the medicinal
agents in a predictable and reproducible manner.
5.Must have a chemical stability over time so as not to
follow alteration of the medicinal agents.
6.The appearance of the tablet should be elegant and its
weight, size and appearance should be consistent
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1- Disintegrating tablets
• Most common type is intended to be swallowed and releases the drug in a
relatively short time after disintegration and dissolution thus fast & complete drug
release in vivo (conventional or plain tablets).
• A disintegrating tablets include the following types of excipients: filler (if the
dose of drug is low), disintegrant, binder, glidant, lubricant and antiadherent.
Steps of drug release from disintegrating tablets
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Conventional tablet may be single layer or multilayer.
Multilayer tablets are prepared by repeated compression of powders and are
made primarily to separate incompatible drugs from each other.
Tablet, multilayer: This is a solid dosage form that contains medicinal
substances that have been compressed to form a multiple-layered tablet or a
tablet-within-a-tablet (the inner tablet being the core and the outer portion
being the shell).
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2- Chewable tablets
• They are chewed so mechanically disintegrated in the mouth.
• The drug is not dissolved in the mouth but swallowed and dissolves in the
stomach or intestine., and it does not leave a bitter or unpleasant after-taste.
Advantages of chewable tablets:
1. Quick and complete disintegration of the tablet - and hence obtain a rapid
drug effect e.g. antacid tablets.
2. Facilitate the intake of the tablet for elderly and children who have difficulty
in swallowing; e.g. vitamin tablets.
3. Can be taken when water is not available.
Mannitol is normally used as a base due to low hygroscopy and more
importantly, it gives pleasant, cooling sensation.
They are similar in composition to conventional tablets except that a disintegrant
is normally not included.
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3- Effervescent tablets
Effervescent tablets are dropped into a glass of water
before administration, during which carbon dioxide
is liberated.
CO2 facilitates tablet disintegration and drug
dissolution; the dissolution of the tablet should be
Complete within a few minutes.
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Advantages of effervescent tablets:
1. Rapid drug action, e.g. analgesic drugs .
2. Facilitate the intake of the drug, e.g. vitamins.
3. Fast drug bioavailability
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Effervescent tablets are usually contained:
Carbonate or bicarbonate and a weak acid such as citric or tartaric.
Flavor and a colourant
A water-soluble lubricant is preferable in order to avoid a film of a
hydrophobic lubricant on the surface of the water after tablet dissolution
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Effervescent tablets should be:
protected from moisture, so that a special package is
needed;
each tablet is completely covered with aluminum
foil and kept in a water-proof container, often
including a desiccant.
Effervescent tablets may be packed in blister packs.
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5. Lozenges
• They are tablets that dissolve slowly in the mouth and so
release the drug dissolved in the saliva.
• They can thus be described as slow-release tablets for
local drug treatment.
Use of lozenges:
Local medication in the mouth or throat in common cold, to
treat cough by:
antiseptics,
antibiotics,
demulcents,
antitussive agents or astringents.
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Lozenges are usually contain:
They are similar in composition to conventional tablets.
2. Disintegrants are not used.
3. Colour, sweetener and flavour.
4. High concentration of Fillers which are mainly sugars,
such as glucose, sorbitol or mannitol.
5. The tablet generally contains sucrose or lactose and
gelatin solution to impart smooth taste
Lozenges are prepared by
• Compaction at high applied pressures in order to obtain a
tablet of high mechanical strength and low porosity which
can dissolve slowly in the mouth.
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6- Sublingual and buccal tablets
Used for drug release in the mouth followed by systemic uptake of the
drug.
• Rapid systemic drug effect can thus be obtained without first-pass liver
metabolism.
• Sublingual tablets are placed under the tongue and buccal tablets are
placed in the side of the cheek.
• They are often small and porous, to facilitate fast disintegration and drug
release.
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7. Dispersible tablet
These tablets disintegrate either rapidly in water, to form a stabilized
suspension, or disperse instantaneously in the mouth to be swallowed without
the aid of water.
It’s preferred for pediatric patients who cannot swallow a solid dosage form
and the AP I is unstable if formulated in liquid formulation.
Also helpful for patients having prolonged illness who are prone to nauseatic
sensations if they have to swallow a tablet.
The added advantage of this formulation is faster onset of action as compared
to standard compressed tablet.
The common examples of API formulated in this dosage form are analgesics
e.g., aspirin, ibuprofen, etc.
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Sublingual tablets are placed under the tongue, Ex.
Nitroglycerin sublingual tablet; it exerts its action within two minutes for
rapid relief of "Angina pectoris" attack, because the sublingual area is rich
in blood supply.
• Also other cardiovascular drugs, barbiturates, and vitamins are
prepared as sublingual tablet dosage form
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Buccal tablets are placed in the side of the check for
absorption through oral mucosa.
• N.B. Buccal tablets may be also prepared for their
local application.
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Tablets used to prepare solution
8. Soluble tablet
•Soluble tablets are uncoated or film- coated tablets.
•Tablets are solids of uniform shape and dimensions,
usually circular, with either flat or convex faces.
• Water soluble tablets are intended for application after
dissolution in water and contain an active ingredient should
be totally soluble in water at used concentrations.
•All the excipients used to formulate these tablets are
required to be completely soluble in water
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9. Hypodermic tablet
These tablets contain one or more readily water soluble
ingredients and are intended to be added in water for injection
of sterile water to form a clear solution which is to be injected
parenterally.
They were widely used by rural physician due to its
portability.
 One bottle of sterile water was carried by the doctor to
prepare many types of injectables.
 It can be used for medicaments whose stability in water is
very poor.
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Tablet Manufacturing
Tablet Compression Machine
•
Design:
1. Hopper for holding and feeding granules or powder to be
compressed.
2. Dies that define the size and shape of the tablet.
3.
Punches for compressing the granules within the dies.
4.
Cam tracks for guiding the movement of the punches.
5.
A feeding mechanism for moving granules from the
hopper into the dies.
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Tablet tooling; punches and dies
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Caplet Shape Dies
We offer caplet shaped dies that are able to efficiently handle
different types of punch pressing applications. These offers
effortless performance and a single punch are capable of creating
multiple dies. These are catering to different engineering and metal
casting industries
Oval Shapes Dies
We offer a vast range of oval shape dies. Used in diverse
industrial application for die casting and injection moulding
processes, these rods are offered in various diameters and
lengths to suit different requirements.
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Pharmaceutical Tablet Dies
Star Shape Tablet Punches
• Heart & Triangular Shape Tablet Punches
• Snap Tap Tablet Punches
• Under Cut With Threading Tablet Punches
• Animal Shape Tablet Punches
• Multi tip Tablet Punches
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Round Shape Dies
We offer a vast range of P.U rods. These sturdy and durable dies are
offered in round shape. Used in diverse industrial application for die
casting and injection moulding processes, these rods are offered in
various diameters and lengths to suit different requirements
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Stages of Tablet Formation
(Compaction Cycle)
Die filling
Gravitational flow of the powder from hopper via
the die table into the die . (The die is closed at its lower
end by the lower
punch).
Tablet formation
The upper punch descends, enters the die ,the powder is
compressed until a tablet is formed.
- after maximum applied force is reached, the upper
punch leaves the powder
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Tablet ejection
The lower punch rises until its tip reaches
the level of the top of the die.
The tablet is subsequently removed from the
die and die table by
a pushing device.
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Tabletting Process
• Basics
–
powders fed into a die
Powder compressed between punches
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Stages of Tablet Formation
(Compaction Cycle)
1. forcing particles into close proximity to each other by
powder compression.
2.
compression takes place in a die by the action of
two punches (lower & upper). Powder compression
The reduction in volume of a powder owing to the
application of a force.
compaction
The formation of a porous specimen of defined
geometry by powder compression
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Tablet press
Single Punch press (Eccentric Press):
bench-top models that make one tablet at a time
(single-station presses)
Disadvantages: Production of small batches of tablets
(200 tablets per minute).
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2- Rotary Press( Multi station Press):
• It was developed to increase the output of tablets
(10 000 tablets per minute), used for Large scale
production.
• It consists of a number of dies and sets of
punches ( from 3 up to 60).
• The dies are mounted in a circle in the die table
and both the die table &
the punches rotate together during operation of the
machine.
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Rotary Press Machine
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The powder is held in a hopper whose lower
opening is located just above the die table.
• The powder flows on to the die table & fed into the
die by a feed frame.
•
During powder compression both punches operate by
vertical movement.
• After tablet ejection, the tablet is knocked away as the die
passes the feed frame.
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Tablet Ingredients (excipients)
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Tablets Excipients
• Their role: ensure that tablets of specified
quality are prepared.
• The common types
of tablet’s excipients are
described in the figure.
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1- Filler or diluent
use: to make required bulk of the tablet .
to provide better tablet properties such as to improve cohesion,
to permit use of direct compression manufacturing
to improve flow
•
Most common fillers in tablets:
1. Lactose; frequently used, water soluble, improves tablet
disintegration.
2. Dicalcium phosphate dihydrate, insoluble in water,
disintegrating agent is a must.
3. Mannitol, dextrose, sucrose, 4. Lactose-anhydrous and spray
dried lactose 5. Directly compressed starch-Sta Rx 1500
6. Hydrolyzed starch-Emdex and Celutab
7. Microcrystalline cellulose-Avicel (PH 101, 102)
.
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Requirements for a good filler:
1.
Chemically inert, biocompatible, cheap.
2.
Non-hygroscopic.
3.
Good biopharmaceutical properties. (water soluble or hydrophilic).
4. Good technical properties (compactability )
5. Have an acceptable taste.
6. They must be free from all microbial contamination.
7. They do not alter the bioavailability of drug.
8. They must be color compatible.
9. They must be non toxic
10. They must be commercially available in acceptable grade
11. They must be physically, chemically stable in combination with the
drug
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2- Disintegrant
Role: to ensure that the tablet, when in contact with a liquid, breaks up
into small fragments, which promotes rapid drug dissolution.
Mode of action:
1. Facilitate water uptake into the pores of tablet,
e.g. surface active agents
2.facilitate rupture of tablet by swelling during water sorption,
e.g. Sodium –starch glycolate, Crosscarmelose- cross linked cellulose;
modified cellulose, Ac-Di-Sol
3. Release of gases to disrupt the tablet structure, normally carbon dioxide,
in contact with water. e.g. effervescent tablets.
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The Method of Disintegrant Addition:
1. Mixed with other ingredients prior to granulation & thus
incorporated within the granules (intragranular addition).
2. Mixed with the dry granules before the complete powder mix
is compacted (extragranular addition).
3.
incorporated as both an intragranular and an extragranular
portion.
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Commonly Used Disintegrants:
1. Starch: - conc. Up to 5-20% of tablet weight
- Swell in contact with water
2. Super disintegrants (e.g. crrosecarmelose, sodium starch
glycolate, Crosspovidone-cross linked povidone)
Swells up to ten fold within 30 seconds when contact water.
3. Clays: bentonite, Veegum 10 % level in coloured tablet only
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3- Binder and adhesive
Role: Ensure that granules and tablets can be formed
with the required mechanical strength ( glue that holds
powders together to form granules ).
- In dry powder form
- In solution
- Examples:
starch mucilage 10-20%,
gelatin solution 10-20%,
gum acacia,
Solution glucose 50%,
Cellulose derivative
Polyvinylpyrrolidone 2% (PVP)
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4- Lubricant
Role:Lubricants prevent adherence of granule/powder to die wall
and to promote smooth ejection from the die after compaction,
reduce inter particle friction and may improve the rate of flow
of the tablet granulation
• Mechanisms of Action :
1. Fluid lubrication.
2. Boundary lubrication.
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Disadvantages of lubricants
•1. Lubricants tend to be hydrophobic, so their levels (typically
0.3 – 2%) need to be optimised:
–
Under-lubricated blends tend to flow poorly and show
compression sticking problems
–
Over-lubricated blends can adversely affect tablet hardness
and dissolution rate, as well as tablet strength.
–
To overcome these problems;
- optimum conc. < 2%
- Addition of SAA
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Commonly used Lubricants
A. Water- insoluble (Fatty acids-based) lubricant
• Magnesium Stearate
• Calcium Stearate
• Stearic Acid, stearic acid salt
• Talc
• Silica derivative- colloidal silica such as Cab-O-Sil,
Syloid, Aerosil in 0.25-3% conc.
• liquid Paraffin, propylene glycol (PG)
B. water-soluble lubricant
- PEG 6000; less effective
- Magnesium lauryl sulfate; good lubrication and surface
wetting effect
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5- Glidants
Role: Improve flowability of the powder & added
during direct compaction and to granulation before
tabletting ( they reducing interparticulate friction).
.
• Common Glidants:
1. Talc (at concentration 1-2 %).
2. silica (0.2 %).
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6- Antiadherant
Role: Reduce adhesion between the powder and
the punch faces & thus prevent particles sticking to the
punches;
• Many lubricants, such as magnesium stearate, have
also antiadherent properties.
Also talc and starch can act as antiadherents.
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7- Sorbent
Definition: are substances that are capable of
sorbing some quantities of fluids in an apparently dry
state. Thus, oils or oil-drug solutions can be
incorporated into a powder mixture which is
granulated & compacted into tablets.
e.g. Microcrystalline cellulose
& silica.
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8- Flavour
Use: give the tablet a more pleasant taste or to
mask an unpleasant one. (Chewable tablet)
• Flavouring agents are often thermolabile
and so cannot be added prior to an operation
involving heat.
•
They are often mixed with the granules
as an alcohol solution.
Ex: Flavour oil
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9- Colourant
Uses: It is added to tablets to aid identification and patient compliance.
Mask of off color drug
Production of more elegant product.
All coloring agents must be approved and certified by FDA.
Two forms of colors are used in tablet preparation – FD &C and D & C
dyes.
These dyes are applied as solution in the granulating agent or Lake
form of these dyes.
Lakes are dyes absorbed on hydrous oxide and employed as dry
powder coloring.
•
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Example: FD & C yellow 6
sunset yellow FD & C
yellow 5- Tartrazine FD & C
green 3Fast Green FD & C
blue 1- Brilliant Blue FD & C
blue 2 - Indigo carmine D & C
red 3- Erythrosine. D & C
red 22 – Eosin Y
It is added during coating.
• It can also be added prior to compaction. ( can be added as an
insoluble powder or dissolved in the granulation liquid
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10- Sweetener
They are used in chewable tablet to exclude or limit the use of
sugar in the tablets.
e.g. Mannitol, 72% as sweet as sucrose.
Saccharin, 500 times sweeter than sucrose.
Disadv.: has a bitter after taste and carcinogenic.
Aspartame, largely replace saccharin.
Disadv.: lack of stability in the presence of moisture.
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