Transcript 《药剂学》课程双语教学方法建设的工作进展

P38
Chapter 4 TABLETS
2007.1.22
1
Introduction - The definition of
tablets
Tablets are (compressed, slab-shaped×) solid dosage
forms consisting of active ingredient(s) and suitable
pharmaceutical excipients. They may vary in size,
shape, weight, hardness, thickness, disintegration and
dissolution characteristics, and in other aspects. They
may be classed, according to the method of
manufacture, as compressed tablets or molded tablets.
Caplets and boluses
Administration route of tablets: orally, sublingually,
buccally, vaginally
2
Introduction – Two common
methods for tablets preparation
compressed tablets: (primarily) are
manufactured with tablet machine
molded tablets: (a limited number)
prepared on a large-scale by
tablet machinery or on a smallscale by manually forcing
dampened powder material into a
mold
3
Introduction – Advantages of
tablets for oral administration
1. conveniently carried
2. readily identified
3. easily taken
4. prescribing flexibility
5. Efficiently and productively manufactured
6. Packaged and shipped at lower cost and with less
breakage
7. More stable and have a longer shelf-life
8. Tablets are sometimes used as the source of a
medicinal agent when it is not otherwise available.
4
Types of tablets
1) Compressed tablets (压制片CT)
2) Multiple compressed tablets (多层压制片MCT)
3) Sugar-coated tablets (糖衣片SCT)
4) Film-coated tablets (薄膜衣片FCT)
5) Gelatin-coated tablets (明胶包衣片)
6) Enteric-coated tablets (肠溶衣片ECT)
7) Buccal or sublingual tablets (口腔用片与舌下片)
8) Chewable tablets (咀嚼片)
5
Types of tablets
9) Effervescent tablets(泡腾片)
10) Molded tablets (模制片MT)
11) Tablet triturates (模印片TT)
12) Hypodermic tablets (皮下片HT)
13) Dispensing tablets (配方片、调剂片DT)
14) Immediate release tablets (速释片IR)
15) Instant disintegrating/dissolving tablets (速崩/溶片)
16) Extended release tablets (缓释片ER)
6
Types of tablets
—— Compressed tablets (CT)
Composition:
 medicinal agent(s) / active ingredient / API / TAI
 pharmaceutical adjuncts/adjuvants/excipients
diluents or fillers:
binders or adhesives:
wetting agents:
disintegrants or disintegrating agents:
7
Types of tablets
—— Compressed tablets (CT)
(continued)
glidants, antiadherents, lubricants(lubricating agents): enhance the flow of the
tableting material, prevent the sticking of fill material to the punches and
dies and produce tablets having a sheen, reduce friction between the tablet
and the die wall (minimize wear of the punches and dies, improve hardness
distribution)
 助流剂：能改善颗粒表面粗糙性(减少颗粒间摩擦力)，增加颗粒流动性的辅
料，作用：使能顺利流入模孔，片重差异合格。
 抗黏着剂：能减轻颗粒对冲模黏附性（最大静摩擦力）的辅料，作用：防止
压片物料黏着于冲模表面，保证冲面光洁度。
 润滑剂：能降低颗粒（或片剂）与冲模孔壁之间摩擦力，改善力的传递和分
布的辅料，作用：增加颗粒的滑动性，使填充良好、片剂的密度分布均匀，
保证推出片剂的完整性。
miscellaneous adjuncts: colorants, flavorants
8
Types of tablets——Multiple
compressed tablets (MCT)
prepared by subjecting the fill
material to more than a single
compression.
1) multiple-layered tablet
The reason to choose this form:
2) tablet-within-a-tablet
Special machines are required.
Double-layered-tablet
Tablet-within-a-tablet
9
Types of tablets —— sugarcoated tablets (SCT)
The purpose:
1) protecting the enclosed drug from the
environment,
2) provides a barrier to objectionable tasting or
smelling drugs,
3) enhances the appearance of the CT and
4) permits the imprinting of identifying
manufacturer’s information.
Disadvantages: time, expertise, larger
(50%), heavier and more shipping cost
10
Types of tablets —— filmcoated tablets (FCT)
FCTs are compressed tablets coated with a thin
layer of polymer capable of forming a skinlike film over the tablet.
The realization of targeted drug release
11
Types of tablets —— gelatincoated tablets
A recent innovation —— GELCAPS——a
capsule-shaped gelatin-coated compressed
tablet
Advantages:
a) one-third smaller than a capsule filled with an
equivalent amount of powder (less bulky)
b) facilitates swallowing
c) more tamper-evident
12
Types of tablets —— entericcoated tablets (ECT)
 provide delayed-release features
 ECTs are designed to pass unchanged through the
stomach with transit to the intestines.
 Scope of application:
a. Drug substance is destroyed by gastric acid.
b. Drug substance is irritating to the gastric mucosa.
c. By-pass of the stomach enhances drug absorption.
13
Types of tablets —— buccal or
sublingual tablets
 Buccal or sublingual tablets are flat or oval tablets
intended to be dissolved in the buccal pouch
(buccal tablets) or beneath the tongue for
absorption through the oral mucosa (sublingual
tablets).
 Scope of application:
the drugs intended for the local effect in the buccal
cavity (buccal tablets)
the drugs that are destroyed by the gastric juice
and/or are poorly absorbed from the GI tract
(sublingual tablets)
14
Types of tablets —— buccal or
sublingual tablets(continued)
 Buccal tablets are designed to erode slowly, while
sublingual tablets are designed to dissolve promptly
and provide rapid drug effects.
 Lozenges (锭剂,糖锭) or troches (compressed
lozenges含片,含锭,糖锭Molded lozenges are
sometimes referred to as pastilles.):.
being slowly dissolved —— usually for localized
effects
15
Types of tablets —— chewable
tablets
 Chewable tablets, which have a smooth, rapid
disintegration when chewed or allowed to dissolve
in the mouth.
 Scope of application:
the administration of tablets of large-size to
children and adults.
e.g. nutrition supplementary dosage form (calcium and vitamins )
16
Types of tablets —— effervescent
tablets
 Effervescent tablets are prepared by compressing
granular effervescent salts that release gas when
in contact with water.
 Scope of application:
water-soluble medicinal substances
17
Types of tablets —— molded
tablets (MT,模制片)
 Molded tablets, as tablet triturates, may be
prepared by molding rather than by compression.
Molded tablets are prepared by forcing dampened
powders under low pressure into die cavities.
 The resultant tablets are very soft, soluble, and are
designed for rapid dissolution.
18
Types of tablets —— tablet
triturates (TT) (模印片,研制片剂)
 Tablet triturates are small, usually cylindrical, molded (MTT)
or compressed tablets (CTT) containing small amounts of
usually potent drugs.
 Features:
a. Only a few tablet triturates are available today, with most of
these TTs produced by tablet compression. The few TTs which
remain are used sublingually, as nitroglycerin tablets.
b. A minimal amount of pressure is applied during their
manufacture. (intended to be readily and completely soluble in
water)
c. A combination of sucrose and lactose is usually the diluent.
d. In the past, TTs were employed in compounding procedures to
provide accurate amounts of potent drug substances.
19
Types of tablets —— hypodermic
tablets (HT) (皮下注射片)
 no longer available
 HT (one type of dispensing tablets, molded tablets and
tablet triturates) were originally used by physicians in the
extemporaneous preparation of parenteral solutions. The
required number of tablets was dissolved in a suitable
vehicle, sterility attained, and the injection performed.
 Advantages: convenience, individualized
 Disadvantages: the difficulty in achieving sterility
20
Types of tablets —— dispensing
tablets (DT) (调剂片，配方片)
 no longer in use
 DTs might better have been termed compounding tablets
because they were used by the pharmacist in
compounding prescription and were not dispensed as such
to the patient.
to provide premeasured accurate amounts of potent drug
substances for compounding multiple dosage units
 DTs had the dangerous potential of being inadvertently
dispensed as such to patient.
21
Types of tablets —— immediate
release tablets (IR)
 Immediate release tablets are designed to
disintegrate and release their medication absent of
any special rate-controlling features as special
coatings and other techniques.
22
Types of tablets —— instant
disintegrating / dissolving tablets (IR)
 Instant-release tablets are characterized by
disintegrating/dissolving in the mouth within one minutes;
some within 10 seconds.
 Tablets of this type are designed for patients (including
pediatric and geriatric patients) who have difficulty in
swallowing tablets.
 After placing them on the tongue they liquefy and the patient
swallows the liquid.
 Techniques used: lyophilization (Zydis); soft direct
compression (WOW-Tab)
 Water-soluble excipients are used to wick water into the tablet
for rapid disintegration/dissolution.
23
Types of tablets —— extended
release tablets (ER)
 Extended-release tablets / controlled release tablets are
designed to release their medication in a predetermined
manner over an extended period of time.
 Expressions such as ``prolonged-action,'' ``repeataction,'' and ``sustained-release'' have also been used to
describe such dosage forms. However, the term
``extended-release'' is used for Pharmacopeial purposes.
24
Types of tablets
—— vaginal tablets
 Vaginal tablets are uncoated and bullet- or ovoidshaped tablets which are inserted into the vagina
for localized effects.
 Scope of application: antibacterials or antifungals
25
CTs —— 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 (模圈) and punches (冲) determine the
physical features of compressed tablets.
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CTs —— 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
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quality standards and compendial requirements
—— tablet weight and Chp weight variation
 The quantity of fill placed in the die cavity of a tablet press
determines the weight of the resulting tablet.
 Chp weight variation: sample amount 20 tablets
 Tablets should comply with the following requirements
stated in the table below.
Average weight
Less than 0.3 g
0.3 g or more
Weight variation limit
± 7.5%
± 5%
28
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.
 Sugar, film and enteric coated tablets
29
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(标示量) and the
RSD is less than 6.0%.
30
quality standards and compendial requirements
—— tablet thickness
 Tablet thickness is determined by the following four
factors:
1) the diameter of die
2) the amount of fill permitted to enter the die
3) the compactability of the fill material
4) the force or pressure applied during compression
 The tableting press affects not only tablet thickness but
also tablet hardness.
 Tablet thickness may be measured by hand gauge (手持标准
尺) or automated equipment.
31
quality standards and compendial requirements
—— tablet hardness and friability (脆碎度)
 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
32
quality standards and compendial requirements
—— tablet hardness and friability (脆碎度)
(continued)
Friability
1) It is used to determine a tablet’s 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%

33
quality standards and compendial requirements
—— tablet disintegration
1) The significance of tablet disintergration
2) Testing apparatus
3) Procedure
34
quality standards and compendial requirements
—— tablet disintegration (continued)
4) Complete disintegration
5) Requirements for different tablets
35
quality standards and compendial requirements
—— tablet disintegration (continued)
The disintegration of enteric-coated tablets:
1) to be tested in simulated gastric fluid (SGF) for
one hour after which no sign of disintegration,
cracking, or softening must be seen.
2) to be tested in simulated intestinal fluid (SIF) for
the time (usually, 1 h) stated in the individual
monograph
36
quality standards and compendial requirements
—— tablet dissolution(溶出度)
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.
37
quality standards and compendial requirements
—— tablet dissolution (continued)
2) The goal of in vitro dissolution is to provide a reasonable
prediction of the product’s in vivo bioavailability.
Basis: The combinations of a drug’s solubility and its intestinal
permeability are supposed as a basis for predicting the
likelihood of achieving a successful in vivo – in vitro
correlation (IVIVC).
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
38
quality standards and compendial requirements
—— tablet dissolution (continued)
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 (加工过程中的) variables
39
quality standards and compendial requirements
—— tablet dissolution (continued)
4) Apparatus 1 and 2 in USP
a) are used principally for immediate release solid dosage forms
b) consist of ① a variable speed stirrer motor, ② a cylindrical
stainless steel basket on a stirrer shaft (apparatus 1) or a
paddle as the stirring element (apparatus 2), ③ a 1000-ml
vessel of glass fitted with a cover having a center port for the
shaft of the stirrer, and three additional ports, two for the
removal of samples, one for the placement of a thermometer,
and ④ a suitable water bath to maintain the temperature of the
dissolution medium in the vessel.
40
quality standards and compendial requirements
—— tablet dissolution (continued)
5) 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
6) 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
41
quality standards and compendial requirements
—— tablet dissolution (continued)
7) 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.
42
Compressed tablet manufacture
•The classification of manufacturing methods
granulation
(制粒法)
direct
compression
(直接压片法)

wet granulation: drugs that are stable to moisture and heat
dry granulation: drugs that are sensitive to moisture and heat
powder ～ : drugs that are sensitive to moisture and heat, fill
material possessing good flowability and compressibility
crystal ～：drug with proper crystal form and good flowability
The requirements for fill material for tablet making
1) flowability (流动性, free-flowing from the hopper into the dies)
2) compressibility (可压性)
43
Compressed tablet manufacture
—— wet granulation
a widely employed method
 The action of granulaiton
1) to provide free-flowing quality
2) to improve powder compressibility by increasing material
density
3) to reduce dust in the air

44
Compressed tablet manufacture
—— wet granulation

The steps of wet granulation
weighing and blending the ingredients(称量与混合)
(liquid binder)
preparing a damp mass(制软材)
screening the damp mass into pellets or granules
drying the granulation(颗粒干燥)
sizing the granulation by dry screening(过筛整粒)
adding lubricant and blending(加润滑剂，混合)
tableting by compression (压片)
45
46
Compressed tablet manufacture
—— wet granulation
Weighing and blending (to be continued)
1) active ingredient, diluent/filler, disintegrant
2) The definition of fillers
Among the fillers used are
lactose, microcrystalline cellulose, starch, powdered
sucrose, and calcium phosphate
a) The choice is based on the material features, its relative
cost, and its compatibility with the other formulation
ingredients.
b) calcium salts —— tetracycline antibiotics (×)
c) lactose —— primary or secondary amine (×)
d) Microcrystalline cellulose has good compactability,
compatibility, consistent uniformity of supply.

47
Compressed tablet manufacture
—— wet granulation
Weighing and blending (continued)
3) The definition of disintegrants (disintegrating agents)
Two characters: water absorbing, swelling. They include:
 starches, 5% to 10% suitable, 20% exerts a rapid disintegration; dried.
 carboxymethyl starch sodium(CMS-Na,羧甲基淀粉钠); primojel
 sodium starch glycolate (羟基乙酸淀粉钠), 5%, swell up to 300% of its
volume;
 microcrystalline cellulose(MCC,微晶纤维素)
 croscarmellose sodium(CCNa,交联羧甲基纤维素钠), 2%;
 Low-Substituted Hydroxypropyl Cellulose(L-HPC,低取代羟丙基纤维素)
 crospovidone(CPVP,交联聚维酮);
4) the method of disintegrants addition (internal, external, internalexternal)

48
Compressed tablet manufacture
—— wet granulation
Definition of disintegrants
Disintegrants are the materials that swell or expand on
exposure to moisture and effect the rupture or breakup
of the tablet in the GI tract.
49
Compressed tablet manufacture
—— wet granulation

The steps of wet granulation
weighing and blending the ingredients(disintegrant)
(liquid binder)
preparing a damp mass
Internal(内加法)
screening the damp mass into pellets or granules
drying the granulation
sizing the granulation by dry screening
External(外加法)
adding lubricant and disintegrant, and blending
tableting by compression
50
Compressed tablet manufacture
—— wet granulation
Preparing the damp mass (制软材)
1) A binder is added to the powder mixture to facilitate the adhesion of
the powder particles.
2) Among the binding agents used are povidone, an aqueous
preparation of corn starch (10-20%), glucose solution (25-50%),
molasses(糖浆), methylcellulose (3%), carboxymethylcellulose, and
microcrystalline cellulose.
3) The proper amount of binding agents to be used
press a portion of the mass in the palm into a ball, the ball crumbles under
moderate pressure. (be compactible by squeezing in the hand)
over-wetting can result in granules that are too hard for proper tableting and
under-wetting can result in tablets that are too soft and tend to crumble.

51
Compressed tablet manufacture
—— wet granulation
Wet screening——Screening the damp mass into pellets or granules
The screen is usually No. 6- to 20-mesh.
The resultant granules are spread evenly on large pieces of paper.
 Drying the granulation (under controlled time, temperature and
humidity)
 Sizing the granulation by dry screening
being passed through a screen of a smaller mesh than that used to
prepare the original granulation
The choosing of granule size (Voids left by too large a granulation
would result in uneven tablets.)
a) smaller tablets: screens from 12- to 20-mesh size
b) normal tablets: screens from 6- to 20-mesh size

52
Compressed tablet manufacture
—— wet granulation
Adding lubricants and blending
1) The method of addition
Lubricant is
dusted over the spread-out granulation through a fine mesh screen.
2) The actions of lubricants
a) to improve the flow of the granulation in the hopper to the die cavity
b) to prevent the adhesion of the tablet formulation to the punches and
dies during compression (to give a sheen to the finished tablet)
c) to reduce friction between the tablet and the die wall during the
tablet’s ejection from the tablet machine
3) the commonly used lubricants
magnesium stearate, calcium stearate, fumed silicon dioxide (气相二
氧化硅), stearic acid, talc, sodium stearyl fumarate (硬脂富马酸钠)
the commonly used quantity: 0.1% to 5%

53
Compressed tablet manufacture
—— All-in-one granulation methods
equipment: fluid-bed granulator or microwave vacuum
processing method
 The fluid-bed granulator performs the following steps;
1) preblending the formulation powder, including active
ingredients, fillers, and disintegrants
2) granulating the mixture by spraying onto the fluidized
powder bed, a suitable liquid binder, as an aqueous
solution of acacia (阿拉伯胶), hydroxypropyl cellulose, or
povidone
3) drying the granulated product to the desired moisture
content.
4) adding lubricants and tableting

54
Compressed tablet manufacture
—— Dry granulation
apply to materials that cannot be prepared by wet granulation due to
their degradation by moisture or by the elevated temperatures required
for drying the granules
 Two methods are used.
1) slugging (压片法)
a) weighing and mixing the ingredients
b) slugging or compressing the powder mixture into large flat tablets or
pellets of about 1 inch in diameter
c) breaking up the slugs by hand or by a mill
d) sizing with a screen of desired mesh
e) preparing tablets after adding disintegrants/lubricants
2) roller compaction (滚压法)
b) pressing the powder mixture between high-pressure rollers at 1 ton to
6 tons of pressure
often preferred over slugging; binding agents: MC or HMC 6 to 12%

55
The classification of tablet presses
(压片机的分类)

Tablet presses
single-punch presses（单冲压片机）
multi-station rotary presses（旋转式多冲压片机）
56
A picture of a single-punch press
manual driving wheel
cylindrical gearing
hopper
cam gearing
belt gearing
feed shoe
electric motor
core components
57
Single-punch tablet press
The main components of singlepunch tablet presses
tablet
hardness
adjustor
hopper

feed
shoe
die
cavity
upper
punch

Core components:
die (模圈)
lower punch (下冲)
upper punch (上冲)
The action of each components
die
lower
punch
tablet ejector
adjustor
tablet weight
adjustor
Schematic diagram of the main
components of single-punch press
58
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
冲压机
a)
upper
punch
b)
c)
tablet
fill
material
lower
punch
d)
die
e)
a)
The compression process on a single
punch machine in cross-section
59
A picture of multistation rotary press
hopper (饲料斗)
feed-frame (饲料框架)
head: upper turret, lower turret, die table
upper turret (上冲固定台面)
die table (模圈固定台面)
lower turret (下冲固定台面)
16,
ZP19 rotary tablet press
19, 27, 33, 37, 41, 49 stations
60
The core components and compression
cycle of rotary presses
filling and adjustment
⑤upper compression
roll
compression
tablet ejection
⑥upper punch raising cam
track of upper punch
feed-frame
A: upper punch
B: die cavity
C: die
D: lower punch
⑨sweep-off blade
The compression is
applied by both the
upper punch and the
lower punch.
③wipe-off blade
track of lower punch
①pull-down cam
②weight control cam
④lower compression roll
⑧ejector knob
⑦lower punch raising cam
The compression cycle of a rotary tablet press
61
Compressed tablet manufacture
—— Tableting of granulation

Multiple-layered tablets are produced by the
multiple feed and multiple compression of fill
material within a single die.
62
Compressed tablet manufacture
—— 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
63
Compressed tablet manufacture
—— Direct compression tableting

The direct compression tableting excipients include:
a) fillers, as spray-dried lactose, microcrystals of alphamonohydrate lactose, sucrose-invert sugar – corn starch
mixtures, microcrystalline cellulose, crystalline maltose麦芽糖,
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
64
Compressed tablet manufacture
—— Direct compression tableting
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

65
Compressed tablet manufacture
——tablet dedusting

to remove traces of loose powder adhering to
tablets following compression.
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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
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Tablet coating

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
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Tablet coating
—— sugarcoating tablets

The sugarcoating of tablets may be divided into
the following steps:
1) waterproofing and sealing (if needed)(隔离层)
2) subcoating(粉衣层)
3) smoothing and final rounding(糖衣层)
4) finishing and coloring (if desired)(色衣层)
5) polishing(打光)
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Tablet coating
—— sugarcoating tablets
The equipment and method for sugarcoating
coating pans of galvanized iron, stainless steel, or copper;
The pans operate at about a 40°angle. The pan is rotated at
moderate speeds, allowing the tablets to tumble over each
other while making contact with the coating solutions which
are gently sprayed onto the tablets. To allow gradual build-up
of the coatings, the solutions are added in portions, with
warm air blown in to hasten drying. Each coat applied only
after the previous coat has dried.
Tablets should be thin-edged and highly convex to allow the
coatings to form rounded rather than angular edges.

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Tablet coating
—— sugarcoating tablets
1) waterproofing and sealing (if needed) (隔离层)
aim: to prevent the components from being adversely affected by moisture;
one or more coats; shellac (虫胶), zein (玉米朊ruan), or a polymer as
cellulose acetate phthalate
2) Subcoating(粉衣层)
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. 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.
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Tablet coating
—— sugarcoating tablets
3) smoothing and final rounding(糖衣层)
aim: to complete the rounding and smooth the coatings
5 to 10 additional coatings of a thick syrup; This syrup is sucrosebased with or without additional components as starch and calcium
carbonate.
4) finishing and coloring(色衣层)
aim: to attain final smoothness and the appropriate color
several coats of a thin syrup containing the desired colorant
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Tablet coating
—— sugarcoating tablets
5) imprinting(印刷)
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(打光)
aim: to render the tablets the desired sheen/gloss/luster
a) pans lined with canvas cloth impregnated with carnauba
wax(巴西棕榈) and/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
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Tablet coating
—— film-coating tablets
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.
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.
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Tablet coating
—— film-coating tablets
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糖精, vanillin香草醛
g) glossant: beeswax
h) volatile solvent: alcohol-acetone mixture
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Tablet coating
—— film-coating tablets
#1: the expense of the volatile solvents and the environmental problem of
the release of solvents
#2: The problem is the slow evaporation of water.
e.g. AQUACOAT (FMC Corporation) contains a 30% ethyl cellulose
pseudolatex with a high solids content and low viscosity.
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
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Tablet coating
—— film-coating tablets
5) Some problems with aqueous film-coating
a) picking and peeling(碎片粘连和剥落)
the appearance of small amounts or large amounts of film
fragments flaking from the tablet surface
b) orange peel effect(起皱、“橘皮”样粗糙面)
roughness of the tablet surface due to failure of spray droplets to
coalesce (愈合、融合、老化)
c) mottling(色斑)
an uneven distribution of color on the tablet surface
d) bridging(桥接)
filling-in of the score-line or indented logo on the tablet by the film
e) tablet erosion(片心磨损)
disfiguration of the core tablet
转至84
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Tablet coating
—— enteric coating
1) Enteric coated solid dosage forms are intended pass through the
stomach intact to disintegrate and release their drug-content for
absorption along the intestines.
2) The rationale(设计原理)
a) transit time
b) thickness of the coatings
c) Usually, an enteric coating is based on factors of pH, resisting
dissolution in the highly acid environment of the stomach but yielding
to the less acid environment of the intestine.
3) Flexibility: a) whole tablets or granules and particles; b) thick or thin; c)
aqueous-based or organic-solvent-based coating systems
4) Among the materials used in enteric coatings are:
pharmaceutical shellac, hydroxypropyl methylcellulose phthalate
(HPMCP), polyvinyl acetate phthalate, diethyl phthalate, and
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cellulose acetate phthalate(CAP)
Tablet coating
—— fluid-bed or air suspension coating
1) The application of fluid bed processing equipment
a) spray coating for powders, granules, beads, pellets
or tablets
b) preparing tablet granulations
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Tablet coating
—— fluid-bed or air suspension coating
2) Different types of fluidized bed system
a) the bottom-spray method (底喷型，Wurster process)
a vertical cylinder; warm air blasts released in the chamber; suitable
for batches of small amount
is particularly recommended for taste masking, enteric release, and
barrier film
b) the top-spray method (顶喷型)
suitable for batches of large amount
is recommended for sustained-release and enteric-release products
c) the tangential-spray method (切线喷型)
used in rotary fluid-bed coater
is recommended for layering coatings, and for sustained-release and
enteric- coated products
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Tablet coating
—— fluid-bed or air suspension coating
3) control variables
a) equipment used
b) the method of spraying (e.g. top, bottom, tangential)
c) spray-nozzle distance from spraying bed
d) spray droplet size
e) spray rate
f) spray pressure
g) volume of fluidization air
h) batch size
i) methods and time for drying
j) air temperature and moisture content in processing compartment
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Tablet coating
—— compression coating
1) in a manner similar to the preparation of multiple
compressed tablets of tablet-within-a-tablet
2) is an anhydrous operation and thus may be safely
employed in the coating of tablets containing a drug that
is labile to moisture.
3) Compared to sugarcoating using pans, compression
coating is more uniform and uses less coating materials.
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Impact of manufacturing changes
on solid dosage forms
1) the changes in formulation and the changes in the method of
manufacture
2) The changes in formulation could involve:
a) the use of starting raw materials, including both the active
ingredient and pharmaceutical excipients
b) the use of different pharmaceutical excipients
c) the use of different quantities of the same excipients in a
formulation
d) the addition of a new excipient to a formulation
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Impact of manufacturing changes
on solid dosage forms
3) The changes in the method of manufacture could involve:
a) use of processing of manufacturing equipment of a
different design
b) a change in the steps or order in the process or method of
manufacture
c) different in-process controls, quality tests, or assay
methods
d) production of different batch sizes
e) employment of different product reprocessing procedures
f) employment of a different manufacture site
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Packaging and storing tablets
1) Tablets are stored in tight containers, in places of low humidity, and
protected from extremes in temperature.
2) Products that are prone to decomposition by moisture generally are
copackaged with a desiccant packet.
3) Drugs that are adversely affected by light are packaged in lightresistant containers.
4) The hardness of certain tablets (including tablets containing
aluminum hydroxide, sodium salicylate, phenylbutazone) may
change upon aging usually resulting in a decreased disintegration
and dissolution rates
5) Certain tablets containing volatile drugs, as nitroglycerin, should be
preserved in tight containers, preferably of glass, at controlled room
temperature.
6) A woman should not handle finasteride tablets because it has the
potential to adversely affect a male fetus.
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Oral administration of solid
dosage forms
1) Taking solid dosage forms with adequate amounts of water is important.
The dangers caused by taking tablets or capsules without water are:
a) the dosage form’s lodging in the esophagus,
b) esophageal ulceration.
Among the drugs of greatest concern in this regard are:
alendronate sodium, aspirin, ferrous sulfate, any nonsteroidal
antiinflammatory drug (NSAID), potassium chloride and tetracycline
antibiotics.
2) Patients who suffer from gastroesophageal reflux disease
3) The relation between oral medication and meals
4) Oral dosage forms that have special coatings
5) The use of crushed tablets or opened capsules
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Other solid dosage forms for
oral administration
1) lozenges
often used as buccal tablet; can be made by compression
or molding;
have a special place in the delivery of medication to
buccal cavity in the treatment of oropharyngeal
candidiasis, cough/cold symptoms and minor sore throat
2) Pills
Pills are small, round, solid dosage forms containing a
medicinal agent and intended to be administered orally.
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