Chapter 4 TABLETS

1
Chapter 4 TABLETS
P38

• 
  2007.1.22

2
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

3
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
  small-scale by manually forcing dampened powder
  material into a mold

4
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.

5
Types of tablets

• 1) Compressed tablets (???CT)
• 2) Multiple compressed tablets (?????MCT)
• 3) Sugar-coated tablets (???SCT)
• 4) Film-coated tablets (????FCT)
• 5) Gelatin-coated tablets (?????)
• 6) Enteric-coated tablets (????ECT)
• 7) Buccal or sublingual tablets (????????)
• 8) Chewable tablets (???)

6
Types of tablets
9) Effervescent tablets(???) 10) Molded tablets
(???MT) 11) Tablet triturates (???TT) 12)
Hypodermic tablets (???HT) 13) Dispensing tablets
(???????DT) 14) Immediate release tablets
(???IR) 15) Instant disintegrating/dissolving
tablets (??/??) 16) Extended release tablets
(???ER)
7
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

8
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)
• ?????????????(????????),??????????,??????????,??
  ?????
• ???????????????(??????)???,???????????????,?????
  ???
• ????????(???)??????????,????????????,??????????,
  ???????????????,???????????
• miscellaneous adjuncts colorants, flavorants

9
Types of tabletsMultiple 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.

10
Types of tablets sugar-coated 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
  manufacturers information.
• Disadvantages time, expertise, larger (50),
  heavier and more shipping cost

11
Types of tablets film-coated tablets (FCT)

• FCTs are compressed tablets coated with a thin
  layer of polymer capable of forming a skin-like
  film over the tablet.
• The realization of targeted drug release

12
Types of tablets gelatin-coated tablets

• A recent innovation GELCAPSa 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

13
Types of tablets enteric-coated 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.

14
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)

15
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 (??,??) or troches (compressed
  lozenges??,??,??Molded lozenges are sometimes
  referred to as pastilles.).
• being slowly dissolved usually for
  localized effects

16
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 )

17
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

18
Types of tablets molded tablets (MT,???)

• 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.

19
Types of tablets tablet triturates (TT)
(???,????)

• 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.

20
Types of tablets hypodermic tablets (HT)
(?????)

• 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

21
Types of tablets dispensing tablets (DT)
(???,???)

• 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.

22
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.

23
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/dissoluti
  on.

24
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,''
  repeat-action,'' and sustained-release'' have
  also been used to describe such dosage forms.
  However, the term extended-release'' is used
  for Pharmacopeial purposes.

25
Types of tablets vaginal tablets

• Vaginal tablets are uncoated and bullet- or
  ovoid-shaped tablets which are inserted into the
  vagina for localized effects.
• Scope of application antibacterials or
  antifungals

26
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 (??) and punches (?) determine the
  physical features of compressed tablets.

27
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

28
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 Weight variation limit
Less than 0.3 g 7.5
0.3 g or more 5
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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

30
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.

31
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
  (?????) or automated equipment.

32
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

33
quality standards and compendial requirements
tablet hardness and friability
(???)(continued)

• 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

34
quality standards and compendial requirements
tablet disintegration

• 1) The significance of tablet disintergration
• 2) Testing apparatus
• 3) Procedure

35
quality standards and compendial requirements
tablet disintegration (continued)

• 4) Complete disintegration
• 5) Requirements for different tablets

36
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

37
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.

38
quality standards and compendial requirements
tablet dissolution (continued)

• 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).
• 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

39
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 (??????) variables

40
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 ? a variable speed stirrer motor,
  ? a cylindrical stainless steel basket on a
  stirrer shaft (apparatus 1) or a paddle as the
  stirring element (apparatus 2), ? 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 ? a suitable water bath to maintain the
  temperature of the dissolution medium in the
  vessel.

41
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

42
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.

43
Compressed tablet manufacture

• The classification of manufacturing methods

• The requirements for fill material for tablet
  making
• 1) flowability (???, free-flowing from the
  hopper into the dies)
• 2) compressibility (???)

44
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

45
Compressed tablet manufacture wet granulation

• The steps of wet granulation

(liquid binder)
46
(No Transcript)
47
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.

48
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,??????)
  primojel
• sodium starch glycolate (???????), 5, swell up
  to 300 of its volume
• microcrystalline cellulose(MCC,?????)
• croscarmellose sodium(CCNa,?????????), 2
• Low-Substituted Hydroxypropyl Cellulose(L-HPC,????
  ?????)
• crospovidone(CPVP,?????)
• 4) the method of disintegrants addition
  (internal, external, internal-external)

49
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.

50
Compressed tablet manufacture wet granulation

• The steps of wet granulation

(liquid binder)
Internal(???)
External(???)
51
Compressed tablet manufacture wet granulation

• Preparing the damp mass (???)
• 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(??),
  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.

52
Compressed tablet manufacture wet granulation

• Wet screeningScreening 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

53
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 tablets ejection from
  the tablet machine
• 3) the commonly used lubricants
• magnesium stearate, calcium stearate, fumed
  silicon dioxide (??????), stearic acid, talc,
  sodium stearyl fumarate (??????) the commonly
  used quantity 0.1 to 5

54
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 (????),
  hydroxypropyl cellulose, or povidone
• 3) drying the granulated product to the desired
  moisture content.
• 4) adding lubricants and tableting

55
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 (???)
• 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 (???)
• 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

56
The classification of tablet presses(??????)

• Tablet presses
• single-punch presses(?????)
• multi-station rotary presses(????????)

57
A picture of a single-punch press
manual driving wheel
cylindrical gearing
hopper
cam gearing
belt gearing
feed shoe
electric motor
core components
58
The main components of single-punch tablet presses

• Core components
• die (??)
• lower punch (??)
• upper punch (??)
• The action of each components

59
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

???
60
A picture of multi-station rotary press
hopper (???)
feed-frame (????)
head upper turret, lower turret, die table
upper turret (??????)
die table (??????)
lower turret (??????)

• 16, 19, 27, 33, 37, 41, 49 stations

61
The core components and compression cycle of
rotary presses
tablet ejection
filling and adjustment
compression
?upper compression roll
?upper punch raising cam
track of upper punch
feed-frame
?sweep-off blade
?wipe-off blade
The compression is applied by both the upper
punch and the lower punch.
track of lower punch
?pull-down cam
?weight control cam
?ejector knob
?lower compression roll
?lower punch raising cam
The compression cycle of a rotary tablet press
62
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.

63
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

64
Compressed tablet manufacture Direct
compression tableting

• The direct compression tableting excipients
  include
• a) fillers, as spray-dried lactose,
  microcrystals of alpha-monohydrate lactose,
  sucrose-invert sugar corn starch mixtures,
  microcrystalline cellulose, crystalline
  maltose???, 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

65
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

66
Compressed tablet manufacturetablet dedusting

• to remove traces of loose powder adhering to
  tablets following compression.

67
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

68
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

69
Tablet coating sugarcoating tablets

• 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(??)

70
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 40angle. 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.

71
Tablet coating sugarcoating tablets

• 1) waterproofing and sealing (if needed) (???)
• aim to prevent the components from being
  adversely affected by moisture one or more
  coats shellac (??), zein (???ruan), 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. 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.

72
Tablet coating sugarcoating tablets

• 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

73
Tablet coating sugarcoating tablets

• 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 wax(????) 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

74
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.

75
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, FDC or DC dyes
• f) sweeteners, flavors, and aromas
  saccharin??, vanillin???
• g) glossant beeswax
• h) volatile solvent alcohol-acetone mixture

76
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) FDC or DC
  lakes and iron oxide pigments
• d) water

77
Tablet coating film-coating tablets

• 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

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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(????)
• 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
  cellulose acetate phthalate(CAP)

81
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

82
Tablet coating fluid-bed or air suspension
coating

• 2) Different types of fluidized bed system
• a) the bottom-spray method (???,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 (???)
• suitable for batches of large amount
• is recommended for sustained-release and
  enteric-release products
• c) the tangential-spray method (????)
• used in rotary fluid-bed coater
• is recommended for layering coatings, and for
  sustained-release and enteric- coated products

83
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

84
Tablet coating compression coating

• 1) in a manner similar to the preparation of
  multiple compressed tablets of tablet-within-a-tab
  let
• 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.

85
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

86
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

87
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 light-resistant 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 forms 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.