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PHARMACEUTICAL SOLID DOSAGE FORMS
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• Drug product means a finished dosage form, e.g.,
  a tablet or capsule that contains a drug
  substance (active ingredient), generally, but not
  necessarily, in association with one or more
  other ingredients.

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VARIOUS ROUTES OF ADMINISTRATION

• ORAL
• - SUBLINGUAL
• PARENTERALS (bypasses GIT)
• INJECTIONS
• DERMAL
• INHALATION
• OTIC
• OPTHALMIC
• RECTAL, VAGINAL

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DOSAGE FORMS
Various Dosage Forms available

• ORAL
• Tablets
• Capsules
• Powders
• Liquid (Syrups, Elixirs Suspensions)
• Lozenges / Pastilles/ Trouches

PARENTERALS Injectables (IM, IV, Infusion,
) Aerosols Dermatologicals (Creams, Ointments)
Pesaries, Suppositories Bougies Eye/ Ear/ Nose
drops
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Solid dosage forms

• Tablets
• Capsules
• Powders
• Lozenges, Pastilles
• Suppositories

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Solid dosage forms

• Tablets
• Solid dosage forms, of varying weight, size, and
  shape, which may be molded or compressed, and
  which contain a medicinal substance in pure or
  diluted form. (Dorland, 28th ed)

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Solid dosage forms

• Capsules
• A solid dosage form in which the drug is
  enclosed in a hard or soft soluble container,
  usually of a form of gelatin.
• - Hard gelatin capsules (Powder filled, enteric
  coated pellets called as SPANSULES)
• Soft gelatin capsules

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Solid dosage forms

• Powders - Substances made up of an aggregation of
  small particles, as that obtained by grinding or
  trituration of a solid drug. (From Dorland,
  28th ed)

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Solid dosage forms

• Lozenges/ Pastilles
• A oral solid preparation containing one or more
  medicaments, usually in a flavored, sweetened
  base which is intended to dissolve or
  disintegrate slowly in the mouth.
• They are placed in the mouth where they slowly
  dissolve and liberate the active ingredient.
  They can contain antiseptics, antibiotics, local
  anaesthetics etc for a topical effect and also
  substances for a systemic effect e.g. vitamins.

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Solid dosage forms

• Suppositories
• Medicated dosage forms that are designed to be
  inserted into the rectal, vaginal, or urethral
  orifice of the body for absorption. Generally,
  the active ingredients are packaged in dosage
  forms containing fatty bases such as cocoa
  butter, hydrogenated oil, or glycerogelatin that
  are solid at room temperature but melt or
  dissolve at body temperature.

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Importance of oral dosage form

• Oral route of administration employed for 90 of
  the drugs used to produce the systemic effect
• Important point considered by the pharma company
  before going to the further development stages
• Ability for Self-administration criteria affects
  the sales of the drug
• Unit dosage forms (one usual dose of drug is
  accurately placed)
• Unlike liquid dosage forms given in multidose
  containers and asked to take with the
  teaspoon/tablespoon
• Chances of error in the Dosage Measurement when
  given in liquid dosage form

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TABLETS

• Advantages of Tablets

• tamper proof dosage form

• greatest dose precision and least content
  variability

• low cost compared to other dosage forms

• product identification is simple

• ease of administration

• can be manufactured with certain release patterns

• best properties of chemical, mechanical and
  microbiological stability

• ease of manufacturing

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TABLETS

• Disadvantages of Tablets

• Some drugs resist compression into dense compacts
  owing to their amorphous nature, low density
  character.

• Bitter tasting drugs may need encapsulation.

• Drugs with poor wetting, slow dissolution
  properties impossible to formulate as they
  increase the absorption in the GIT

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Tablet properties

• 1) should be elegant having its own identity
  while being free of defects such as chips,
  cracks, discoloration, contamination
• 2) should have strength to withstand the rigors
  of mechanical shock encountered during
  production, packing, shipping and dispensing.
• 3) should have the chemical and physical
  stability to maintain its physical attributes
  over time.
• 4) must be able to release the medicinal agent
  in the body in a predictable and reproducible
  manner.

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TABLETS

• Types and Classes of Tablets

Single / Multi layered

• - Uncoated Tablet

Chewable Tablets
Sublingual Tablets
Effervescent Tablets
Lozenges/ Pastilles

• - Coated Tablets

Film coated Tablets
Sugar coated Tablets
Enteric coated Tablets
- Sustained Release/ Extended Release/ Controlled
Release Tablets
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Types of Tablets

• Multi layered Tablets
• These are compressed tablets made by one or more
  compression cycles.

• Chewable Tablets
• These are compressed tablets made by adding
  sweetners and flavorants so that the tablet can
  be chewed.

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Types of Tablets

• Sublingual Tablets
• These are small flat tablets to be placed below
  the tongue for dissolving rapidly and absorb
  readily.

• Effervescent Tablets
• In addition to the drug substance they contain
  sodium carbonate. In presence of water, these
  additives react, liberating carbon dioxide that
  acts as a disintegrator and produces
  effervescense .

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Types of Tablets

• Film-coated Tablets
• These are compressed tablets having a thin layer
  or film of water soluble material. Film coating
  protects materials sensitive to oxidation and
  enhances the look of the product.

• Sugar-coated Tablets
• These are compressed tablets having a sugar
  coating. Done to mask the objectionable taste and
  protects materials sensitive to oxidation and
  enhances the look of the product.

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Types of Tablets

• Enteric-coated Tablets
• These are compressed coated tablets with
  substances that resist solution in gastric fluid
  but disintegrate in the intestine. It can be used
  for substances that get destroyed in the stomach,
  for those that irritate the mucosa or as means of
  delayed release of the medicine.

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Types of Tablets

• Controlled release/ Sustained release and
  Extended Release Tablets
• Sustained release
• A tablet that releases its active ingredient in
  specified doses at timed intervals. Also called
  sustained-release tablets.
• Delayed Release
• products are modified-release, but by definition
  are not extended-release. They involve the
  release of discrete amount(s) of drug some time
  after drug administration, e.g. enteric-coated
  products, and exhibit a lag time during which
  little or no absorption occurs.

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Ingredients used for Tablet manufacture

• Active ingredient
• is the main drug

• Inactive ingredient
• additional agents added to give shape and size
  and improve the properties of the drug

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Ingredients used for Tablet manufacture

• Inactive Ingredients

• Diluent
• An inert substance to give bulk to make the
  tablet a practical size for compression (Maize
  Starch, Lactose, Cellulose)

• Binders/ Granulators
• Agents used to impart cohesive qualities to the
  powder material. (Maize Starch, gelatin,
  Cellulose)

• Lubricants
• Materials added to prevent adhesion of the
  tablet material to the surface of the dies and
  punches, reduce interparticle friction,
  facilitate ejection of the tablet from the die
  cavity (Talc, Magnesium stearate, calcium
  stearate)

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Ingredients used for Tablet manufacture

• Glidants
• Substance which improves the flow
  characteristics of a powder mixture. (Colloidal
  Silicon dioxide, Talc)

• Disintegrants
• Substance added to facilitate its break-up or
  disintegration after administration. (Sodium
  starch glycollate, croscarmellose, crospovidone)

• Colouring agent/ Colorant
• used either to improve the appearance, or
  control product during its preparation. (FD C
  colourants)

• Solvents
• to make granules. (Purified Water, Isopropyl
  Alcohol)

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Ingredients used for Tablet manufacture

• Flavouring agent/ Flavorant
• used for masking taste. (Peppermint, aspartame)

• Ingredients added for coating

• Coating agent
• used to coat the tablet after compression.
  (Hydroxypropyl methyl celllulose, Wincoats)

• Solvents
• to dissolve the coating material/ to carry the
  coating material. (Methylene chloride, Isopropyl
  Alcohol)

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Process of Manufacture of Tablets

• Dispensing / Weighing
• The raw materials (active/ inactive ingredients)
  are weighed in the stores in presence of a
  production personnel and the stores incharge and
  dispensed to the production department.
• Equipment used- Weighing balance

• Sifting/ Sieving
• The raw materials (active/ inactive ingredients)
  are sifted through respective sieve to get the
  desired particle size.
• Equipment used- Mechanical sifter

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Process of Manufacture of Tablets

• Mixing / Milling
• The raw materials (active/ inactive ingredients)
  are mixed in blenders to attain uniform
  distribution. Or they are milled to attain the
  required particle size and then sieved again.
• Equipments used- Cone blender, Planetary mixer,
  Colloidal mill

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Process of Manufacture of Tablets

• Granulation
• Density may affect compressibility, tablet
  porosity, dissolution and other properties.
  Dense, hard granules require higher compressible
  loads to produce a cohesive compact
• Strength and Friability Granule is an
  aggregation of component particles held together
  by bonds of finite strength.

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GRANULATION CHARACTERISTICS

• Flow Properties
• may result from forces acting between solid
  particles.
• Response angle
• Hopper Flow Rates
• Compaction (the process of consolidating and
  compacting powder or granule material to form a
  tablet

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GRANULATION CHARACTERISTICS

• Particle size and shape
• Affects weight, weight variation,, disintegration
  time, granule friability, granulation
  flowability, drying rate characteristics of wet
  granulation
• Depends in-turn upon formulation ingredients,
  concentrations, equipment and processing
  conditions
• Surface Area
• Inverse relation normally exists between particle
  size and surface area

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GRANULATION

• BASIC CHARACTERISTICS OF TABLET
• Compactness
• Physical Stability
• Rapid Production capability
• Chemical Stability
• efficacy
• for a material to be compressed into the tablet
• It has to have a fluidity for transport of
  material through the hopper, into and through the
  feed frame and into the dies
• and compressibility

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GRANULATION

• Physical form that allows the tablet material to
  flow smoothly and uniformly is
• SPHERES
• Offer minimum contact surface between themselves
  and walls of the machine parts

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GRANULATION

• A pharmaceutical process that attempts to improve
  the flow of powdered materials by forming a
  spherelike or regularly shaped aggregates called
  granules. It also converts the mixture of
  powders, which have poor cohesion, into
  aggregates capable of compaction
• .

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Manufacture of granulation

• Compression Granulation
• Wet Granulation
• Direct Compression

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Process of Manufacture of Tablets

• Types of Granulation
• 1) Compression granulation/ dry granulation
• carried out when the drug is sensitive to heat,
  moisture or both. Eg Aspirin or vitamins
• Formulations are prepared for tabletting by
  compression granulation.
• Compression granulation involves the compaction
  of the components of a tablet formulation by
  means of tablet press or specially designed
  machinery followed by milling and screening,
  prior to final compression into the tablet.
• Slugs are formed in the tablet press which are
  then screened or milled to form tabletting
  material.
• Equipment used- chilsonator

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Process of Manufacture of Tablets

• Types of Granulation
• 2) Wet granulation
• forms the granules by binding the powders
  together with an adhesive/ binder. The technique
  employs a solution, suspension or slurry
  containing a binder, which is usually added to
  the powder mixture.
• Once the granulating liquid has been added,
  mixing continues until a uniform dispersion is
  attained and all the binder has been activated.
• A drying process is required in all wet
  granulation procedures to remove the solvent.
• Equipment used Mixer granulator (Diosna)

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Process of Manufacture of Tablets

• 3) Direct Compression
• Few crystalline substances such as NaCl, KBr,
  may be compressed directly.
• done on tablets in which the drug itself
  constitutes the major portion of the total tablet
  weight.
• the compression of a single ingredient may
  produce tablets that do not disintegrate. Then
  other components are added.
• A direct compressible diluent is an inert
  substance that can be compacted with little
  difficulty and may compress even when quantities
  of drugs are mixed with it.

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Process of Manufacture of Tablets

• Drying
• Granules are dried at specified temperature for
  specified time.
• Equipments used - Fluidized Bed drier
• Lubrication
• The granules are lubricated with lubricating
  agents.
• Compression
• The granules alongwith the glidants, lubricants,
  disintegrants are then compressed to form the
  tablet of desired shape and size.
• Compression machine
• Tooling set consists of a die and upper and
  lower punches.
• Equipments used Rotary compression machines
• Sent to QC for Analysis
  
  

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Compression

• At the start of a compression cycle granulation
  stored in a hopper empties into the feed-frame
  (A), which has several interconnected
  compartments. These compartments spread the
  granulation over a wide area to provide time for
  the dies (B) to fill. The pull down cam (C)
  guides the lower punches to the bottom of their
  vertical travel, allowing the dies to overfill.
  The punches then pass over a weight control cam
  (E), which reduces the fill in the dies to the
  desired amount. A wipe off blade (D) at the end
  of the feed frame removes the excess granulation
  and directs it around the turrent and back into
  the front of the feed-frame. Next, the lower
  punches travel over the lower compression roll
  (F) while simultaneously the upper punches ride
  beneath the upper compression roll (G)

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Compression

• The upper punches enter a fixed distance into the
  dies, while the lower punches are raised to
  squeeze and compact the granulation within the
  dies. To regulate the upward movement of the
  lower punches, the height of the lower pressure
  roll is changed. After the moment of compression,
  the upper punches are withdrawn as they follow
  the upper punch raising cam (H) the lower
  punches ride up the cam (I), which brings the
  tablets flush with or slightly above the surface
  of the dies. The exact position is determined by
  a threaded bolt called the ejector knob. The
  tablets strike a sweep-off blade affixed to the
  front of the feed-frame (A) and slide down a
  chute into receptacle. At the same time, the
  lower punches re-enter the pull down cam (C) and
  the cycle is repeated.

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Process of Manufacture of Tablets

• Coating
• Equipment used Coating pans
• The compressed tablets are then coated with the
  coating agent dissolved in the solvent.
• Polishing
• Coated tablets after drying are polished on the
  polishing belt and visually inspected for any
  defects.

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Flow Chart for Tablet Manufacture
Weighing active / inactive ingredients
Sifting/ Sieving
Direct compression
Mixing/ Milling
Wet granulation/ dry granulation
Drying
Lubrication / Glidant
Lubrication / Glidant
Uncoated
Inspection
Compression
After QC analysis of fp
After QC analysis
Packing
Coating
Polishing
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Problems during Tablet manufacturing/ processing

• Chipping
• Tablets getting chipped from the sides during
  compression.
• Capping and lamination
• Capping is term used to describe the partial or
  complete separation of the top or bottom crowns
  of a tablet from the main body of the tablet.
• Picking and Sticking
• Picking is used to describe the surface material
  from a tablet that is sticking to and being
  removed from the tablets surface by a punch.
• Sticking refers to tablet material adhering to
  the die wall.

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Problems during Tablet manufacturing/ processing

• Spotting / Mottling
• Mottling is an unequal distribution of color on
  a tablet, with light or dark areas standing out
  in an otherwise uniform surface.
• Weight variation
• The weight of tablet being compressed is
  determined by the amount of granules in the die
  prior to compression.

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Problems during Tablet manufacturing/ processing

• Granule size and Size distribution before
  compression
• Variations in the ratio of small and large
  granules and in the magnitude of difference
  between the granule sizes influence how the void
  spaces between particles are filled. Thus the
  apparent volume in the die is same, different
  proportions of large and small particles may
  change the weight of fill in each die.
• Punch variation
• When punches are of different sizes, even small
  difference, the fill in each die varies because
  the fill is volumetric.

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Problems during Tablet manufacturing/ processing

• Poor flow
• When the granules do not flow readily, it tends
  to move spasmodically through the feed frame so
  that the dies are incompletely filled.
• Poor Mixing
• Sometimes the lubricants and glidants are not
  thoroughly distributed. The flow of particles is
  then impaired and the granules do not move
  efficiently into the dies.
• Hardness variation
• Hardness depends on weigh of material and space
  between the upper and lower punches at the moment
  of compression
• If the volume of the material or the distance
  between the punches varies hardness is likewise
  inconsistent.
• Double impression
• improper punch die movement coordination may
  result in double impression of the monogram or
  engraving on the tablet and hamper its
  appearance.

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Tests/ Evaluations conducted on Tablets
General Appearance General Appearance of a
tablet, its visual identity and overall elegance
is essential for consumer acceptance. Tablet
size, shape, colour, presence/ absence of an
odour, taste, surface texture, consistency and
legibility of any identifying marks.
Hardness and friability Tablet require certain
amount of strength and resistance to friability
to withstand mechanical shocks of handling in
manufacture, packaging and shipping. Tablet
hardness is the force required to break a tablet
in diametric compression test. Instrument for
Hardness testing Monsanto Hardness
tester. Instrument for Friability testing Roche
friabilator
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Hardness and friability

• The hardness of a tablet, like its thickness, is
  a function of the die fill and compression force
• At a constant die fill, the hardness values
  increase and thickness decreases as additional
  compression force is applied
• Tablet hardness is not an absolute indicator of
  strength since some formulations, when compressed
  into very hard tablets, tend to cap on
  attrition, losing their crown portions Another
  measure of a tablets strength, its friability,
  is often measured

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Hardness and friability

• Another measure of a tablets strength, its
  friability, is often measured
• Tablets that tend to powder, chip and fragment
  when handled lack elegance and consumer
  acceptance and can create excessively dirty
  processes in such areas of manufacturing as
  coating and packaging
• They can also add to a tablets weight variation
  or content uniformity problems

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Tests/ Evaluations conducted on Tablets
Weight variation Weight variation is conducted
by weighing 20 tablets individually, Calculating
the average weight and comparing the individual
tablet weights to the average. Instrument used
Weighing balance

• Content uniformity
• To check the amount of drug present in each
  tablet. 10 tablets
• are assayed individually.
• Factors contributing to content uniformity
• Non-uniform distribution of the drug throughout
  the powder
• mixture or granulation stage.
• 2) Segregation of powder mixture or granulation
  during various
• manufacturing stages.
• 3) Tablet weight variation.

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Tests/ Evaluations conducted on Tablets

• Disintegration
• Breakdown of tablet into smaller particles or
  granules.
• Instrument Disintegration apparatus as per USP/
  BP.
• Apparatus 6 glass tubes, open at the top and
  held against a 10 mesh screen at the bottom end
  of the basket rack assembly.
• Method 1 tablet is placed in each of the tube
  and the basket rack
• Assembly is positioned in water/ simulated
  gastric fluid or simulated
• Intestinal fluid at 37C 2C, such that the
  tablet remains below the
• surface of the liquid. A standard motor-driven
  device is used to move the basket assembly
  containing the tablets up and down.
• All the tablets must disintegrate and all the
  particles must pass through the 10 mesh screen.
• Sometimes discs may be used on the tablet to
  prevent the tablet from floating.

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Tests/ Evaluations conducted on Tablets

• Dissolution
• Is conducted to determine the rate of drug
  absorption for acidic drug
• moieties that are absorbed high in the GI tract.
  
• Objectives
• Release of drug from tablet is as close as 100.
• Rate of drug release is uniform from batch to
  batch.
• Instrument used USP Apparatus 1 2
• Apparatus 1
• Basket type
• Tablet placed inside the basket, basket is
  immersed into the flask
• containing the Dissolution medium. The flask is
  cylindrical with a
• hemispherical bottom. The flask is maintained at
  a temperature
• at 37C 0.5C. Motor is adjusted for specific
  speed and the samples
• of fluid are withdrawn at intervals to determine
  the amount of drug in
• solution.

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Tests/ Evaluations conducted on Tablets

• Dissolution contd.
• Apparatus 2
• Same as Apparatus 1 except that the basket is
  replaced by a paddle, formed from a blade and a
  shaft as a stirring element. The tablet is
  allowed to sink to the bottom of the flask before
  stirring.
• The test tolerance is expressed as percentage of
  the labeled amount of drug dissolved in the time
  limit.

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