Short notes on tablets I
In this first article on
tablets I am going to provide some important points regarding tablet
formulation.
ü I: Advantages,
disadvantages, tablet defects and the excipients used in the formulation of
tablets
ü II: Evaluationparameters and types & classes of tablets.
Second part of this topic
will be provided in the next post. So, for short notes on second point please
refer the next post.
ADVANTAGES
OF TABLETS
Oral route of
administration is the most preferred route for the administration of drugs for
their systemic effects. Tablets are mostly preferred for this due to following
advantages:
· Unit dosage forms
· Greatest dose precision
· Least content variability
· Lowest cost
· The lightest and the most compact oral dosage forms
· Easy transportation as compared to liquids
· Product identification is easy
· Can be formulated as modified drug release product
· Better suited to large-scale production
· Best chemical, mechanical and microbiological stability
· Unit dosage forms
· Greatest dose precision
· Least content variability
· Lowest cost
· The lightest and the most compact oral dosage forms
· Easy transportation as compared to liquids
· Product identification is easy
· Can be formulated as modified drug release product
· Better suited to large-scale production
· Best chemical, mechanical and microbiological stability
DISADVANTAGES OF TABLETS
·
Properties of some drugs to resist
compression due to low-density and flocculant nature.
· Drugs having characteristics like poor
wettability, large dosage and sow dissolution are difficult to formulate as
tablets.
· Drugs having bitter taste, objectionable
odor and moisture absorption tendency need encapsulation. In this case capsule
is a better choice.
TABLET DEFECTS
Tablet defects
|
Description
|
Mottling
|
Non-uniformity of colors of tablets.
Uneven distribution of color particles
in tablet.
|
Capping
|
Partial or complete separation of top or
bottom crowns of tablet from main body.
|
Lamination
|
Separation of a tablet into two or more
distinct layers.
|
Sticking
|
Tablet material adhering to die wall
|
Picking
|
Surface material of tablet sticking to
& being removed (picked) by punch.
|
EXCIPIENTS USED IN THE TABLET
FORMULATION
Excipients
are the inert materials which assist in the formulation of any dosage form with
desired properties. In the formulation of tablets excipients having properties
such as (a) diluent, (b) binder, (c) disintegrant and (d) lubricants are used.
Let’s
see some important points on which questions were asked in previous year GPAT
examinations. (and of course some new points!)
DILUENTS
Also known as fillers and bulking
agents.
Primary role:
To produce bulk (added when drug dose is inadequate for compression).
Important points regarding diluents:
1.
If calcium salt (such as calcium
phosphate) is used as diluent in the tetracycline product, what will happen?
This condition was noticed while marketing
of tetracycline antibiotic tablet where drug showed less than half the
bioavailability of standard product.
Tetracycline + Calcium salt àThis divalent cation
(Ca+2) binds to the active site of tetracycline and causes
inactivation à reduction in absorption
of drug and less or no therapeutic effect.
2.
Maillard
reaction: Also known as browning reaction.
Lactose
is a commonly used diluent.
When it was used as a diluent for
formulation of amine drugs, in presence of metal stearate lubricant (magnesium
stearate), the product (tablet) showed brown discoloration with time.
Amine drugs (API) + Lactose (diluent) + metal stearate
(lubricant) à Brown discoloration of tablet.
3.
Hydrous
lactose: Undergoes Maillard reaction
Anhydrous
lactose: Does not undergo Maillard reaction.
4.
Difference
between hydrous and anhydrous
Hydrous:
Compounds/salts that contain bound water as water of crystallization.
Anhydrous:
No bound water. Anhydrous compounds are proe to moisture absorption when
exposed to humidity.
5.
When wet granulation is employedà if lactose is used then its hydrous form is preferred.
Direct
compression àSpray-dried
lactose.
6.
Directly
compressible starches
à
Sta-Rx 1500, Emdex, Celutab.
7.
Diluents
used in chewable tablets à Mannitol, Emdex,
Celutab, Sucrose.
8.
Sucrose
based diluents:
i) Sugartab
(90
to 93% sucrose + 7 to 10% invert sugar)
ii) DiPac
(97%
sucrose + 3% modified dextrins)
iii) NuTab
(95%
Sucrose + 4% invert sugar + small amount of corn starch and magnesium stearate)
9.
Avicel
à Microcrystalline cellulose
Grades
à PH 101: powder
PH
102: granules
BINDERS AND ADHESIVES
Dry form à to
form cohesive compacts while direct compression.
Liquid from à to
form granules.
1.
Natural
gums: Acacia, Tragacanth (10-25% aqueous solutions are
used).
Acacia+Tragacanth or alone each compound.
Gelatin + Acacia.
2.
Most
common granulating agent: Starch paste.
Liquid glucose (50% aqueous solution)
Sucrose solution (50-74% concentration)
3. Modified
natural polymers: Alginate and cellulose derivatives
(Methylcellulose, Hydroxypopyl methylcellulose & Hydroxypropyl cellulose)
4.
Direct compression à
dry powders à
binder capabilities
Granulation à
aqueous solutions à
adhesive properties
DISINTEGRANTS
Role: Promote
disintegration (breaking) of tablet upon contact with water/ gastrointestinal
fluids.
Mechanism: Draws water inside of
tablet à swelling àbursting
of tablet into fragments à dissolution of fragments à
absorption of drug
1.
Starch
à 5 to 20% of tablet
weight
2.
Substituted
carboxymethyl starches à Pimogel
and Explotab
(used in concentration 1 to 8%, Optimum concentration
is 4%)
3.
Pre-gelatinized
starches à 5%
4.
Clays
à Veegum HV and
Bentonite (10%)
5.
Ac-Di-Sol
à an internally
cross-linked form of Sodium Carboxymethyl Cellulose.
LUBRICANTS,
ANTIADHERENTS AND GLIDANTS
- Lubricants: These reduce friction between surface of tablet and die wall during tablet ejection.
- Antiadherents:
Reduce
sticking/ adhesion of powder or granules to the punch and die.
- Glidants:
Reduce friction between particles and helps in easy flow of
granules or powder.
- 1. Lubricant property: Stearic
acid salts > Stearic acid
- 2. Colloidal silica: Cab-O-Sil, Syloid or Aerosil
MATERIAL
|
PROBLEM
|
Mineral
oil (Sprayed on granules)
|
Produce
oil spots
|
Talc
|
Traces
of iron.
Causes
breakdown of some dugs due to catalytic effect of iron.
|
COLORS,
FLAVORS AND SWEETENERS
COLORS:
Role
à disguising of off-color drugs
à product identification
è Production of elegant product
Dyes:
FD&C
and D&C dyes à applied as solutions
Lakes:
Employed
as dry powders
FLAVOURS:
è Limited to chewable tablets &
tablets that are intended to dissolve in mouth.
è Water soluble flavours à
poor stability à little acceptance
è Flavour oils à
0.5 to 0.75 %
SWEETENERS:
è Used in chewable tablets.
è Mannitol à
72% as sweet as Sucrose
è Saccharin à
500 times sweeter than Sucrose
Disadvantage:
Bitter aftertaste and carcinogenic.
è Aspartame à 200
times sweeter than sucrose
Disadvantage:
unstable in presence of moisture.
Reference:
The
theory and Practice of Industrial Pharmacy by Lachman & Liberman.
This is what I currently
got for you guys. I will update this article with new information regularly.
If you have any questions
regarding this article or suggestion, then feel free to leave a comment below.
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