Chapter
8: TABLETS
Ø
Solid
dosage forms containing medicinal substances with or without suitable diluents
Ø
Most
widely used dosage form
ADVANTAGES:
- Precision
of dosage form
- Durability
of physical characteristics for extended period of storage
- Stability
of chemical and physiological activity
- Convenience
of administration
DISADVANTAGES:
- Irritant
effects of the GI mucosa by some solids (aspirin)
- Possibility
of bioavailabilty problems resulting from slow disintegration and
dissolution
CLASSIFIED
ACCCORDING TO THE METHOD OF MANUFACTURE:
- Compressed
Tablets – usually prepared by large scale production methods
- Molded
tablets – small scale production
COMPRESSED
TABLETS
-
Are formed in
the process of pressing powdered crystalline or granular substances alone or in
combination with excipients to form a compact adherent of pre-determined shape
3
Main methods of manufacture:
1.
WET
granulation
a.
Weighing
and blending
b.
Preparing
dampened powder
c.
Screening
of damp mass to form pellets and granules
d.
Drying of
granules
e.
Sizing by
dry screening
f.
Adding
lubricant and blending
i.
Most used
lubricant: Magnesium stearate
g.
Compressed
to form tabs
2.
FLUID BED
PROCESS
a.
Fluidized
air
3.
DRY
granulation
a.
For those
that degradein moisture
i.
Slugging
ii.
Roller
compaction
iii.
Tabletting
1.
LAMINATION-
horizontal striation
2.
CAPPING-
top of the tablet separates from whole, not enough bond
4.
Direct
Compression
a.
Likes of
Potassium chloride,possess free flowing properties that enable to compress
directly
Types
of compressed tablets
1.
SUGAR
COATED TAB
a. Contains sugar coating
b. Such coating may be colored
and are beneficial in covering up drug substances possessing objectionable
tastes and odors and in protecting materials sensitive to oxidation
I.
Waterproofing
and Sealing
1.
Using
shellac
II.
Subcoating
III.
Smoothing
IV.
Finishing
and coloring
V.
Polishing
2.
FILM
COATED TABLETS
a. Covered with an thin layer of
water soluble material
b. A number of polymeric
substancs with film formingproperties may be used
c. Film coating imparts the
same general characteristics as sugar coating with added advantage if a
greatly reduced time period required for the coating operation
I.
Film
former: cellulose acetate phthalate
II.
Alloying
substance: water solubiliy/permeability :Polyethylene glycol
III.
Plasticizer:
Flexibility and elasticity- Castor oil
IV.
Surfactant
V.
Opaquants
colorants
VI.
Sweeteners
VII.
Glossant:
luster: beeswax
VIII.
Volatile
solvent: allow spread over the tab; rapid evaporation: alcohol mixed with
acetone
*due
to environmental concerns:
Aquacoat
is used. Water- based
30%
ethyl cellulose pseudolatex
PROBLEMS
with FILM COATING
1.
Picking-
appearance of small amounts of film fragments
2.
Peeling-
large amounts
3.
Orange
Peel Effect- roughness of the tab, failure to coalesce
4.
Mottling-
Uneven distribution of color
5.
Bridging-
Filling in score line or intended logo
6.
Tablet
erosion- Disfiguration of tablet due to over exposure to coating soln
3.
ENTERIC
COATED TAB
a. Coated with the substances
that resist solution in gastric fluid but disintegrate in the intestines
b. Enteric coating can be used
for tablet containg during the substances which are inactive or destroyed in
the stomach for which irritate the mucosa or as means of delayed release of the
medication
I.
USES
PHTHALATES of sorts
II.
To
dissolve at pH 4.8 and greater
4.
MULTIPLE
COMPRESSED TAB
a. More than 1 compression
cycles
b. The tablets are prepared by 2
REASONS:
:To separate
physically or chemically incompatible ingredients
:To
produce repeat action /prolonged action tablet
c. Can be used to separate
incompatible drug to give an enteric coating to core tablets
5.
PROLOGED-
ACTION TAB
a. Formulated to release the
drug substances in a manner to provide medication over the period of time
I.
TYPES OF
PROLONGED ACTION TAB
1.
DELAYED—ACTION-
release of drug substances is prevented for an interval of time after
administration or until the certain physiological conditions exist
2.
REPEAT-ACTION
TAB- periodically release a complete dose of drug substances to the GI fluids
3.
EXTENDED-
RELEASE TAB-continuously release increment of the contained drug substances in
GI fluid
6.
TABLETS
FOR SOLUTION
a. To be used for preparing
solutions or imparting given characteristics to solutions must be labeled to
indicate that they are not be swallowed
EXAMPLE:
HALAZONE TABLET FOR SOLN
7.
EFFERVESCENT
TAB
a. In addition to the drug
substance, these may contain sodium bicarbonate and an organic acid (tartaric
acid and citric acid)
b. In the presence of water,
these additives reacts liberating CO2 which acts as DISINTEGRATOR and produces
EFFERVESCENCE
8.
TABLETED
SUPPOSITORIES OR INSERTS
a. Occasionally vaginal
suppositories such as METRONIDAZOLE tablets areprepared by compression
b. In this case, as well as for
any tablet intended for administration other than by swallowing, the label must
indicate the manner which it is to be used.
9.
BUCCAL
AND SUBLINGUAL TAB
a. Small flat oval tab
b. Tablets that are intended for
buccal: by insertion into the buccal pouch dissolve and erode slowly
SUBLINGUAL
a.
NITROGLYCERIN
AND ISOPROTERENOL HCL placed under tongue
b.
Dissolve
rapidly and drug substances are readily absorbed by this term of administration
10.
CHEWABLE
TABS
a. Pleasant tastingtablets
b. NO DISINTEGRANTS
c. Wet granulation and
compression
d. MANNITOL- MOST used excipient
for chewables 50% of the entire wt
e. XYLITOL- mau be used, sweeter
than mannitol; has desiabe negative heat of soln leaving COOL MOUTH FEEL upon
dissolution
f.
MOLDED
TABLETS OR TABLET TRITURATES
-usually
made from moist material using a triturate mold which gives them the shape of
cut sections of a cylinder
-
such tabletsmust be completely and rapidly soluble
-
problems arising from compression of these tablets falure to find a lubricant
that is completely water soluble
1.
DISPENSING TAB
-
provide a convenient quantity of poten drug that can be incorporated readily
into powder and liquids thus circumventing the necessity to weigh small scale
-
supplied primarily as a convenience for EXTEMPORANEOUS COMPOUNDING and should
NEVER BE USED AS DOSAGE FORM
2.
HYPODERMIC TAB
-
soft readily solube tablets tht were originally used for preparation of
solutions to be injected
-
since stable parenteral solution are non available for most drug substances,
there is no justification for the use of hypodermic tablets for injection
-their
use is discouraged due to RESULTING SOLUTIONS NOT STERILE
COMPRESSED
TAB
-
WELL-MADE COMPRESSED TAB POSSESSES THESE ATTRIBUTES:
1.
ability to withstand the rigors of the mechanical fxn involved in the
production packaging shipment and dispensing
2.
freedom from defects such as cracks chipped edges , discoloration , specking
and contamination
3.
Reasonable chemical and physical stability during average storage conditions
4.
Ability to release the medicament in a reproducible and predictable manner
The
components that must be added to the therapeutic ingredient are classified
acoording to their function and grouped into
- ESSENTIAL
COMPONENTS impart satisfactory characteristics to the formulation
1.
BINDER-
glue powders together and cause to form granules ; mpart cohesive properties to
powdered materials
2.
DILUENT-
make up the major portion of tab
3.
DISINTEGRANTS
- help tablet break up and dissolves to release the medicament for rapid
dissolution
b. COMPRESSION AIDS IMPART SATISFACTORY compression characteristics
1.
GLIDANTS –enable flow from hopper on to the table press to the die for consistent
tile
2.
LUBRICANTS- aid in releasing the compresses tablet from the die
3.
ANTI-ADHESIVES- to prevent the formation of residue films of tablet
granulations in punches
c. SUPPLEMENTARY COMPONENTS give additional desirable physical characteristics
to finished tablet
1.
COLOR- added for its aesthetic value to provide a control during manufacture
and to distinguish one product from another
2.
FLAVOR- same reason as color
3.
SWEETENING AGENT- enhance taste of finished product especially when chewed
4.
ADSORBENTS- capable of holding quantities of fluids in an apparently dry state
DILUENT
1.
Lactose USP (Hydrous/Anhydrous)
-
inexpensive
-
readily soluble
-
stable and generally inert
Net
softened by frictional force of compression due to high MELTING POINT 202
DISADVANTAGE
1.
BINDERS may have to be added when presence of drugs or some other substances
interfere with cohesion
2.
LUBRICANTS required
2.
STARCHES
-
derived from the WHEAT CORN RICE and POTATO
-
ALSO UED AS BINDERS and DISINTEGRANTS
-
provide moisture balance even though the water content 12-14 %
-
they stabilize hygroscopic drugs and protect tablets of such material from
deterioration before use
3.
MANNITOL (powder, granules)
-
ADVANTAGES
>
highly desirable for WATER-SENSITIVE DRUGS
>appropriate for chewable tab because its sweet taste and
negative heat of soln
-DISADVANTAGES
>Expensive
4.
SORBITOL
-ADVANTAGES
>
direct tableting
-DISADVANTAGES
>Very
hygroscopic above 65% relative humidity
>it
may be blended with mannitol or other excipient to reduce moisture pick-up
5.
SUCROSE
ADVANTAGES
Ø
Provide
additional sweetness
Ø
Serves
as BINDER since it has cohesive properties
Ø
Contributes
to dissolution of the tablet since it is readily soluble
DISADVANTAGES
Ø
Somewhat
hygroscopic
Ø
Tends to
form BROWN in contact with acidic and basic substances
6.
MICROCRYSTALLINE CELLULOSE (Avicel)
ADVANTAGES
Ø
Used for
compression formulation
DIADVANTAGES
Ø
Presence
of drug may necessitate addition of LUBRICANTS to formulation
BINDER
-
Efficiency of
binders is dependent on the choice of the proper binding agent, quantity used
and form of the binder when added
-
Choice of binder
depends on the binding drug required to form granules and its compatibility
with other ingredients as revealed by stability studies
-
Too much binder
will result in hard tablets which will cause excessive wear if punches and dies
because of heavy pressure required to compact the granules
-
Mottling of tab
surface may also occur by these tablets are colored
-
Binders used as
a solution is more effective the same amount of binder which is dispensed in
dry form and moistened with the solvent
-
The binding soln
can easily penetrate the film of adsorbed air coating each particle of a
powerblend
RECOMMENDED
BINDING SOLUTIONS ARE:
|
1.
STARCH PASTE
|
10-20%
W/W
|
|
2.
AQUEOUS GELATIN SOLN
|
10-20%
W/W
|
|
3.
AQUEOUS GLUCOSE SOLN
|
25-50%
W/W
|
|
ALCOHOLIC
SOLUTION OF ETHYL CELLULOSE
|
5
% W/W
|
DISINTEGRANTS
-
The rate with
which the active ingredient is released from the tablet mtrix is measures by
disintegration time of the tablet
-
Major factor
which affects disintegration time is the disintegrants, its selection ,
quantity and mode of addition of the formulation
-
Other factor
which can also affect disintegration time:
1. BINDERS
2. TABLET HARDNESS
3. LUBRICANT
-
Some material
which functions as an disintegrants or chemically chemically classified as
1. STARCH (CORN AND POTATO)
-
Most popular
disintegrators
-
It has a great
affinity for water and swell when moistened , thus facilitating the rupture of
the tablet matrix. However, the starch does not swell at this temperature found
in the gastric fluids
2.
CLAYS (Bentonite and Veegum
3.
CELLULOSE
- Methylcellulose
- sodium
carboxymethylcellulose
-
microcrystalline cellulose
4. ALGIN
-
Alginic acid
-
sodium alginate
5. gums
-
Locust bean
-
Karaya
-
Guar
-tragacanth
6.
Effervescent mixture
-
mixtures of the sodium bicarbonates and as acidulant such as tartaric acid or
citric acid will effervesce when added to water
-
gas pressure due to evolution of CO2 results in rapid disintegration of the
tablet
Instantly
Disintegrating or Dissolving Tablets
-
Dissolves
approximately 15 to 30 seconds
-
Lyophilized
foam- Zydis delivery system
-
Putting drug
foam into a mold
USP
Standards
1.
Weight
variation: 10 tablets weighed. Average. Assayed
2.
Tablet
thickness
3.
Hardness
and Friability- minimum 4 kg force—SATISFACTORY TABLET
4.
Durability-
FRIABILATOR- MAXIMUM WEIGHT LOSS OF less than 1% ACCEPTABLE
5.
Disintegration
test; 3o minutes usually; nitroglycerin tab 2 min; buccal 4hrs
OTHER
SOLID DOSAGE FORMS
1.
Lozenges-
self care meds
2.
Lolliops-
Fentanyl Actiq ( Cephalon) – Breakthrough pain for cancer
3.
Pills-
small round
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