2. Tablet is defined as a compressed solid dosage form
containing medicaments with or without excipients. According to the
Indian Pharmacopoeia Pharmaceutical tablets are solid, flat or
biconvex dishes, unit dosage form, prepared by compressing a drug
or a mixture of drugs, with or without diluents. They may vary in
size, shape, weight, hardness, thickness, disintegration and
dissolution characteristics, and in other aspects. They may be
classyfied, according to the method of manufacture, as compressed
tablets or molded tablets.
3. Advantages of Tablet Dosage Form Production aspect Large
scale production atLarge scale production at lowest costlowest cost
Easiest and cheapest toEasiest and cheapest to package and
shippackage and ship High stabilityHigh stability User aspect
(doctor, pharmacist, patient) Easy to handlingEasy to handling
Lightest and most compactLightest and most compact Greatest dose
precision &Greatest dose precision & least content
variabilityleast content variability
4. Disadvantages of Tablet Difficult to swallow in case of
children and unconscious patients. Some drugs resist compression
into dense compacts, owing to amorphous nature, low density
character. Drugs with poor wetting, slow dissolution properties,
optimum absorption high in GIT may be difficult to formulate or
manufacture as a tablet that will still provide adequate or full
drug bioavailability. Bitter testing drugs, drugs with an
objectionable odor or drugs that are sensitive to oxygen may
require encapsulation or coating. In such cases, capsule may offer
the best and lowest cost.
5. Different Types of tablets (A) Tablets ingested orally: 1.
Compressed tablet, e.g. Paracetamol tablet 2. Multiple compressed
tablet 3. Repeat action tablet 4. Delayed release tablet, e.g.
Enteric coated Bisacodyl tablet 5. Sugar coated tablet, e.g.
Multivitamin tablet 6. Film coated tablet, e.g. Metronidazole
tablet 7. Chewable tablet, e.g. Antacid tablet (B) Tablets used in
oral cavity: 1. Buccal tablet, e.g. Vitamin-c tablet 2. Sublingual
tablet, e.g. Vicks Menthol tablet 3. Troches or lozenges 4. Dental
cone
6. (c) Tablets administered by other route: 1. Implantation
tablet 2. Vaginal tablet, e.g. Clotrimazole tablet (D) Tablets used
to prepare solution: 1. Effervescent tablet, e.g. Dispirin tablet
(Aspirin) 2. Dispensing tablet, e.g. Enzyme tablet (Digiplex) 3.
Hypodermic tablet 4. Tablet triturates e.g. Enzyme tablet
(Digiplex)
7. Tablet Ingredients In addition to active ingredients, tablet
contains a number of inert materials known as additives or
excipients. Different excipients are: Diluent Binder and adhesive
Disintegrents Lubricants and glidants Colouring agents Flavoring
agents Sweetening agents
8. EXCIPIENTS FOR COMPRESSED TABLETS Compressed tablets usually
contain a number of pharmaceutical adjuncts, known as excipients,
in addition to the medicinal substance. The use of appropriate
excipients is important in the development of the optimum tablets.
Excipients determine the bulk of the final product in dosage forms
such as tablet, capsule, etc., the speed of disintegration, rate of
dissolution,release of drug, protection against moisture, stability
during storage, and compatibility . Excipients should have no
bioactivity, no reaction with the drug substance, no effect on the
functions of other excipients, and no support of microbiological
growth in the product .
10. A. DILUENTS Diluents increase the volume to a formulation
to prepare tablets of the desired size. Widely used fillers are
lactose, dextrin, microcrystalline cellu- lose starch,
pregelatinized starch, powdered sucrose, and calcium
phosphate.
11. Properties of Diluents 1. They must be non toxic. 2. They
must be commercially available in acceptable grade 3. There cost
must be low 4. They must be physiologically inert 5. They must be
physically & chemically stable by themselves & in
combination with the drugs. 6. They must be free from all microbial
contamination. 7. They do not alter the bioavailability of drug. 8.
They must be color compatible.
12. B.BINDERS Binders promote the adhesion of particles of the
formulation. Such adhesion enables preparation of granules and
maintains the integrity of the final tablet. As listed in the
Table, Commonly used binding agents include: starch, gelatin and
sugars (sucrose, glucose, dextrose, and lactose).
14. C. Disintegrates Added to a tablet formulation to
facilitate its breaking or disintegration when it contact in water
in the GIT. Example: Starch- 5-20% of tablet weight. Starch
derivative Primogel and Explotab (1-8%) Clays- Veegum HV, bentonite
10% level in colored tablet only Cellulose Cellulose derivatives-
Ac- Di-Sol (sodium carboxy methyl cellulose) Alginate PVP
(Polyvinylpyrrolidone), cross-linked
15. D. LUBRICANTS Lubricant is a substance capable of reducing
or preventing friction, heat, and wear when introduced as a film
between solid surfaces. It works by coating on the surface of
particles, and thus preventing adhesion of the tablet material to
the dies and punches. Glycerylmonostearate(USP/NFCH2(OH)CH(OH)CH2O2
CC17H35) is one example of a lubricant. Lubricants play more than
one role in the preparation of tablets as described below.
16. 1. Lubricants improve the flow of granules in the hopper to
the die cavity. 2. Lubricants prevent sticking of tablet
formulation to the punches and dies during formulation. 3.
Lubricants reduce the friction between the tablet and the die wall
during the tablets ejection from the tablet machine. 4. Lubricants
give a sheen to the finished tablets.
17. Commonly used lubricants include: talc, magnesium stearat,
calcium stearate ,stearic acid, hydrogenated vegetable oils and
(PEG).
18. E. WETTING AGENTS Water molecules attract each other
equally in all directions. Water molecules on the surface, however,
can only be pulled into the bulk water by water molecules
underneath, since there are no water molecules to pull in the
opposite direction. The surface tension of water is strong enough
to support the weight of tiny insects such as water striders. The
surface ten-sion in action can be visualized by placing a small
drop of alcohol on a thin layer of water. Alcohol with lower
surface tension mixes with water causing reduction in the surface
tension in the local region. Owing to the higher surface tension of
water in the neighbor, water is pulled from the alcohol dropped
region into the neighbor, and this leads to the formation of a dry
spot in the middle of the water layer.
19. Compressed tablet manufacture The classification of
manufacturing methods wet granulation: suitable for drugs that are
stable to moisture and heat dry granulation: suitable for drugs
that are sensitive to moisture and heat powder compression :
suitable for drugs that are sensitive to moisture and heat, fill
material possessing, good flowability and compressibility
granulation direct compression crystal compression suitable for
drugs with proper crystal form and good flowability
25. The steps of wet granulation (liquid binder) Internal
External
26. The classification of tablet presses Tablet presses: a.
single-punch presses b. multi-station rotary presses
27. The main components of single-punch tablet presses Core
components: die lower punch upper punch
28. The basic mechanical process of tableting with single-punch
presses a) filling material b) scraping away the excessive
granulation c) forming a tablet by compression d) pushing up the
tablet to stage surface e) shoving the tablet aside
29. A picture of multi-station rotary press hopper head: upper
turret, lower turret, die table upper turret die table lower
turret
30. The core components and compression cycle of rotary presses
A: upper punch B: die cavity C: die D: lower punch The compression
is applied by both the upper punch and the lower punch. The
compression cycle of a rotary tablet press
31. Direct compression tableting Suitable for 1) granular
chemicals possessing free flowing and cohesive properties e.g.
potassium chloride 2) chemicals added with special pharmaceutical
excipients which impart the necessary qualities for the production
of tablets by direct compression
32. The direct compression tableting excipients include: a)
fillers, as spray-dried lactose, microcrystals of alphamonohydrate
lactose, sucroseinvert ,sugar corn starch mixtures,
microcrystalline cellulose, crystalline malt and dicalcium
phosphate; d) disintegrants, as direct-compression starch, sodium
carboxymethyl starch, cross-linked carboxymethylcellulose fiber,
and cross-linked polyvinylpyrrolidone; c) lubricants, as magnesium
stearate and talc; d) glidants, fumed silicon dioxide
33. Processing problems Capping is the partial or complete
separation of the top or bottom crowns of a tablet from the main
body of the tablet. Lamination is separation of a tablet into two
or more distinct layers. Both of these problems usually result from
air entrapment during processing. Picking is removal of a tablets
surface material by a punch. Sticking is adhesion of tablet
material to a die wall. These two problems result from excessive
moisture or substances with low melting temperatures in the
formulation
34. Mottling is an unequal color distribution on a tablet, with
light or dark areas standing on otherwise uniform surface. This
results from use of a drug with a color different from that of the
tablet excipients or from a drug with colored degradation products.
Weight variation-granule size distribution, poor fiow,punch
variation Hardness variation Double impression-monograms or
engraving on punch
35. Tablet coating The reasons for tablet coating 1) to protect
the medicinal agent against destructive exposure to air and/or
humidity; 2) to mask the taste of the drug; 3) to provide special
characteristics of drug release; 4) to provide aesthetics or
distinction to the product; 5) to prevent inadvertent contact by
nonpatients with the drug substance
36. The general methods involved in coating tablets are as
follows 1) sugarcoating tablets 2) film-coating tablets 3) enteric
coating 4) pan coating 5) fluid-bed or air suspension coating 6)
compression coating
37. The sugarcoating of tablets may be divided into the
following steps: 1) waterproofing and sealing (if needed) 2)
subcoating 3) smoothing and final rounding 4) finishing and
coloring (if desired) 5) polishing
38. film-coating machine
39. 1) waterproofing and sealing (if needed) aim: to prevent
the components from being adversely affected by moisture; one or
more coats; shellac , zein , or a polymer as cellulose acetate
phthalate 2) Subcoating aim: to bond the sugar coating to the
tablet and provide rounding a) 3 to 5 subcoats of a sugar-based
syrup are applied. The sucrose and water syrup also contains
gelatin, acacia, or PVP.
40. b) When the tablets are partially dry they are sprinkled
with a dusting powder, usually a mixture of powdered sugar and
starch but sometimes talc, acacia, or precipitated chalk as well.
c) Then drying the tablets. Repetition (15 to 18 times) the
subcoating process until the tablets are of the desired shape and
size.
41. 3) smoothing and final rounding aim: to complete the
rounding and smooth the coatings 5 to 10 additional coatings of a
thick syrup; This syrup is sucrose-based with or without additional
components as starch and calcium carbonate. 4) finishing and
coloring aim: to attain final smoothness and the appropriate color
several coats of a thin syrup containing the desired colorant
42. 5) imprinting aim: to impart identification codes and other
distinctive symbols to the product The imprint may be debossed,
embossed, engraved, or printed on the surface with ink. 6)
polishing aim: to render the tablets the desired sheen/gloss/luster
a) pans lined with canvas cloth impregnated with carnauba waxand/or
beeswax b) Pieces of wax may be placed in a polishing pan c)
light-spraying of the tablets with wax dissolved in a nonaqueous
solvent
43. Film-coating 1) The disadvantages of sugarcoating process
a) time-consuming b) requiring the expertise of highly skilled
technicians c) doubling the size and weight of the original
uncoated tablets d) may vary in size from batch to batch and within
a batch e) large tablets are not as easily swallowed as are small
tablets.
44. 2) The advantages of film-coating process a) coated tablets
having essentially the same weight, shape, and size as the
originally compressed tablet b) The coating is thin enough to
reveal any identifying monograms. c) far more resistant to
destruction by abrasion than are sugar-coated tablets d) the
coating may be colored to make the tablets attractive and
distinctive.
45. 3) The components of nonaqueous film-coating solutions: a)
film former: e.g. CAP b) alloying substance: to provide water
solubility or permeability to the film e.g. PEG c) plasticizer: to
render flexibility and elasticity to the coating e.g. castor oil d)
surfactant: to enhance spreadability of the film e.g.
polyoxyethylene sorbitan derivatives e) opaquants and colorants:
e.g. titanium dioxide, FD&C or D&C dyes f) sweeteners,
flavors, and aromas: saccharin, vanillin g) glossant: beeswax h)
volatile solvent: alcohol-acetone mixture
46. 4) The components of a typical aqueous film-coating
solutions: a) film-forming polymer (7-18%): e.g. cellulose ether
polymers as HPMC, HPC and MC b) plasticizer (0.5-2.0%): e.g.
glycerin, propylene glycol, PEG, diethyl phthalate, and dibutyl
subacetate c) colorant and opacifier (2.5-8%): FD&C or D&C
lakes and iron oxide pigments d) water
47. 5) Some problems with aqueous film-coating a) picking and
peeling the appearance of small amounts or large amounts of film
fragments flaking from the tablet surface b) orange peel effect
roughness of the tablet surface due to failure of spray droplets to
coalesce c) mottling an uneven distribution of color on the tablet
surface d) bridging filling-in of the score-line or indented logo
on the tablet by the film e) tablet erosion disfiguration of the
core tablet
48. 5) Some problems with aqueous film-coating a) picking and
peeling the appearance of small amounts or large amounts of film
fragments flaking from the tablet surface b) orange peel effect
roughness of the tablet surface due to failure of spray droplets to
coalesce c) mottling an uneven distribution of color on the tablet
surface d) bridging filling-in of the score-line or indented logo
on the tablet by the film e) tablet erosion disfiguration of the
core tablet
49. The reasons for capping, splitting or laminating of tablets
1) air entrapment 2) not immaculately cleaned or not perfectly
smoothed punches 3) too great a proportion of fine powder 4)
Tablets have aged or have been stored improperly
50. quality standards and compendial requirements The apparent
physical features of compressed tablets: 1) shape: round, oblong,
unique 2) thickness: thick or thin 3) diameter: large or small 4)
flat or convex 5) unscored or scored in halves, thirds and
quadrants 6) engraved or imprinted with an identifying symbol
and/or code number 7) coated or uncoated 8)colored or uncolored 9)
number of layer. The die and punches determine the physical
features of compressed tablets.
51. quality standards and compendial requirements Other
physical specifications and quality standards: tablet weight weight
variation content uniformity tablet thickness tablet hardness
tablet disintegration drug dissolution in-process controls
verification after the production
52. quality standards and compendial requirements tablet weight
and Chp weight variation Chp weight variation: sample amount 20
tablets Tablets should comply with the following requirements
stated in the table below. Average weight Weight variation limit
Less than 0.3 g 7.5% 0.3 g or more 5%
53. quality standards and compendial requirements tablet weight
and Chp weight variation The procedure of weight variation
determination in Chp: Weigh accurately 20 tablets and calculate the
average weight, then weigh individually each of the 20 tablets.
Compare the weight of each tablet with the labelled tablet (if no
labelled weight is stated, compare the weight of each tablet with
the average weight calculated). No more than 2 of the individual
weights exceed the weight variation limit stated in the table above
and none doubles the limit.
54. quality standards and compendial requirements tablet
hardness and friability Tablet hardness 1)The greater the pressure
applied, the harder the tablets. 2) The hardness required by
different tablets a) lozenges and buccal tablets: hard (dissolve
slowly) b) the tablets for immediate drug release: soft 3)
measurement a) special dedicated hardness testers b)
multifunctional equipment
55. quality standards and compendial requirements content
uniformity applys to potent drug of low dose. USP method, 10
tablets are individually assayed for their content. The amount of
active ingredient in each tablet lies within the range of 85% to
115% of the label claim and the RSD is less than 6.0%.
56. quality standards and compendial requirements tablet
hardness and friability Friability 1) It is used to determine a
tablets durability 2) Method: allowing the tablets to roll and fall
within the rotating apparatus (friabilator); determine the loss in
weight; 3) requirement: weight loss 1%
57. Tablet Hardness Tester
58. Friability Tester
59. Dissolution Tester
60. Disintigration Tester
61. quality standards and compendial requirements tablet
dissolution 1) The importance of in vitro dissolution test a) to
guide the formulation and product development process toward
product optimization b) to monitor the performance of manufacturing
process c) to assure bioequivalence from batch to batch d) as a
requirement for regulatory approval for product marketing for
products registered with the FDA and regulatory agencies of other
countries.
62. 2) The goal of in vitro dissolution is to provide a
reasonable prediction of the products in vivo bioavailability.
Basis: The combinations of a drugs solubility and its intestinal
permeability are supposed as a basis for predicting the likelihood
of achieving a successful in vivo in vitro correlation
(IVIVC).
63. Considered are drugs determined to have: a) high solubility
and high permeability (IVIVC may be expected.) b) low solubility
and high permeability (IVIVC may be expected.) c) high solubility
and low permeability d) low solubility and low permeability
64. 3) The formulation and manufacturing factors affecting the
dissolution of a tablet a) the particle size of the drug substance
b) the solubility and hygroscopicity of the formulation c) the type
and concentration of the disintegrant, binder, and lubricant used
d) the manufacturing method, particularly, the compactness of the
granulation and the compression force e) the in-process
variables
65. 4) Test method a) A volume of the dissolution medium is
placed in the vessel and allowed to come to 37 0.5 . b) The stirrer
is rotate at the specified speed. c) At stated intervals, samples
of the medium are withdrawn for chemical analysis 5) Requirement
for rate of dissolution The specific required rates of dissolution
are different for tablets containing different medicinal agents.
e.g. not less than 85% of the labeled amount is dissolved in 30
minutes
66. 6) Inconsistencies in dissolution occur not between dosage
units from the same production batch, but rather between batches or
between products from different manufacturers. Pooled dissolution
testing has emerged. This process recognizes the concept of batch
characteristics and allows pooled specimens to be tested.