2. Pharmaceutical Preparations
• DEFINITION
Pharmaceutical preparations are medicinal products generally consisting of active
substances that may be combined with excipients, formulated into a dosage form
suitable for the intended use, where necessary after reconstitution, presented in a
suitable and appropriately labelled container.
3. Types of Pharmaceutical Preparations
• Pharmaceutical preparations may be licensed by the competent authority, or
unlicensed and made to the specific needs of patients according to
legislation. There are 2 categories of unlicensed pharmaceutical preparations:
• — extemporaneous preparations, i.e. pharmaceutical preparations
individually prepared for a specific patient or patient group, supplied after
preparation;
• — stock preparations, i.e. pharmaceutical preparations prepared in advance
and stored until a request for a supply is received.
Unlicensed Preparations should comply the pharmacopoeial requirements,
risk assessment and ethics guidelines.
4. PRODUCTION
• Manufacture/preparation must take place within the framework of a suitable quality
system and be compliant with the standards relevant to the type of product being
made. Licensed products must comply with the requirements of their license.
• Formulation
• During pharmaceutical development or prior to manufacture/preparation, suitable
ingredients, processes, tests and specifications are identified and justified in order to
ensure the suitability of the product for the intended purpose. This includes
consideration of the properties required in order to identify whether specific ingredient
properties or process steps are critical to the required quality of the pharmaceutical
preparation.
• Active substances and excipients
• Active substances and excipients used in the formulation of pharmaceutical
preparations comply with the requirements of the relevant pharmacopoeial
monographs,
• physicochemical characteristics of active substances and functionality-related
characteristics (FRCs) ofexcipients (e.g. particle-size distribution,
viscosity, polymorphism)
5. • Microbiological quality
• The formulation of the pharmaceutical preparation and its container must ensure
that the microbiological quality is suitable for the intended use.
• A suitable container is selected. Consideration is given to the intended use of the
preparation, the properties of the container, the required shelf-life, and
product/container incompatibilities.
• Stability requirements of pharmaceutical preparations are dependent on their
intended use and on the desired storage time.
• TESTS
• Relevant tests to apply in order to ensure the appropriate quality of a particular
dosage form are described in the specific dosage form monographs.
6. • Appearance: size shape and colour.
• Identification
• identification of the active substance(s);
— identification of specific excipient(s), such as preservatives;
— purity tests (e.g. investigation of degradation products, residual solvents or other
related impurities, sterility.
— safety tests (e.g. safety tests for biological products).
• Uniformity; Pharmaceutical preparations presented in single-dose units comply
with the test(s) as prescribed in the relevant specific dosage form monograph.
• ASSAY
• Unless otherwise justified and authorised, contents of active substances and
specific excipients such as preservatives are determined in pharmaceutical
preparations. Limits must be defined and justified.
• Suitable and validated methods are used. If assay methods prescribed in the
respective active substance monographs are used, it must be demonstrated that
they are not affected by the presence of the excipientsand/or by the formulation.
• Reference standards
• LABELLING AND STORAGE
• The relevant labelling requirements given in the general dosage form monographs apply.
7. Powders and Granules
• A formulation in which the drug substance is mixed with other
powdered excipients to produce a final product.
• The function of excipients depends upon the function of esch
ingredients.
• Colouring, flavouring and sweetening agents may be added.
8. Types
• Oral use
• External use
• Inhalation. Give examples
• Insufflation
• Powder for oral suspension
• Powder for injection
May be bulk or in divided doses….
9. Advantages & Disadvantages
• Stability
• Convenient for large dose
• Faster bioavialability
• Less convenient to carry
• Masking of taste
• Not suitable forb potent drugs
• Not suitable for drugs causing
damage or inactivated in the
stomach.
11. • DEFINITION
• Tablets are solid preparations each containing a single dose of one or more
active substances. They are obtained by compressing uniform volumes of
particles or by another suitable manufacturing technique, such as extrusion,
moulding or freeze-drying (lyophilisation). Tablets are intended for oral
administration. Some are swallowed whole, some after being chewed, some
are dissolved or dispersed in water before being administered and some are
retained in the mouth where the active substance is liberated.
• The particles consist of one or more active substances with or
without excipients such as diluents, binders, disintegrating agents, glidants,
lubricants, substances capable of modifying the behaviour of the preparation
in the digestive tract, colouring matter authorised by the competent authority
and flavouring substances.
• Tablets are usually straight, circular solid cylinders, the end surfaces of which
are flat or convex and the edges of which may be bevelled. They may have
break-marks and may bear a symbol or other markings. Tablets may be coated.
12. Categories of tablets for oral use
1. — uncoated tablets;
2. — coated tablets;
3. — gastro-resistant tablets;
4. — modified-release tablets;
5. — effervescent tablets;
6. — soluble tablets;
7. — dispersible tablets;
8. — orodispersible tablets;
9. — chewable tablets;
10.— tablets for use in the mouth;
11.— oral lyophilisates.
13. Uncoated Tablets
• Uncoated tablets include single-layer tablets resulting from a single
compression of particles and multi-layer tablets consisting of concentric or
parallel layers obtained by successive compression of particles of different
composition. The excipients used are not specifically intended to modify
the release of the active substance in the digestive fluids.
14. COATED TABLETS
• Coated tablets are tablets covered with one or more layers of mixtures of various substances such as natural or
synthetic resins, gums, gelatin, inactive and insoluble fillers, sugars, plasticisers, polyols, waxes, colouring matter
authorised by the competent authority and sometimes flavouring substances and active substances. The
substances used as coatings are usually applied as a solution or suspension in conditions in which evaporation of
the vehicle occurs. When the coating is a very thin polymeric coating, the tablets are known as film-coated
tablets.
• Coated tablets have a smooth surface, which is often coloured and may be polished; a broken section, when
examined under a lens, shows a core surrounded by one or more continuous layers with a different texture.
15. GASTRO-RESISTANT TABLETS
• Gastro-resistant tablets are delayed-release tablets that are intended to resist the
gastric fluid and to release their active substance(s) in the intestinal fluid. Usually
they are prepared from granules or particles already covered with a gastro-
resistant coating or in certain cases by covering tablets with a gastro-resistant
coating (enteric-coated tablets).
16. MODIFIED-RELEASE TABLETS
• Modified-release tablets are coated or uncoated tablets that contain
special excipients or are prepared by special procedures, or both, designed to
modify the rate, the place or the time at which the active substance(s) are
released.
• Modified-release tablets include prolonged-release tablets, delayed-release
tablets and pulsatile-release tablets.
17. EFFERVESCENT TABLETS
• Effervescent tablets are uncoated tablets generally containing acid substances
and carbonates or hydrogen carbonates, which react rapidly in the presence of
water to release carbon dioxide. They are intended to be dissolved or dispersed
in water before administration.
18. • SOLUBLE TABLETS
• Soluble tablets are uncoated or film-coated tablets. They are intended to be
dissolved in water before administration. The solution produced may be slightly
opalescent due to the added excipients used in the manufacture of the tablets.
• DISPERSIBLE TABLETS
• Dispersible tablets are uncoated or film-coated tablets intended to be dispersed
in water before administration, giving a homogeneous dispersion.
19. • Orodispersible tablets
• Orodispersible tablets are uncoated tablets intended to be placed in the mouth
where they disperse rapidly before being swallowed.
• CHEWABLE TABLETS
• Chewable tablets are intended to be chewed before being swallowed.
• TABLETS FOR USE IN THE MOUTH
• Tablets for use in the mouth are usually uncoated tablets. They are formulated to
effect a slow release and local action of the active substance(s) or the release and
absorption of the active substance(s) at a defined part of the mouth.
• ORAL LYOPHILISATES
• Oral lyophilisates are solid preparations intended either to be placed in the
mouth or to be dispersed (or dissolved) in water before administration.
20. Tablets administered by other routes
•Implantation tablets:
• depot tablets to be implanted subcutaneously under the skin for prolonged
release of the therapeutic agent. these tablets should be sterile.
•Vaginal tablets:
• They are tablets prepared by compression intended to be inserted into the
vaginal cavity by special insertion device. It contains soluble substances with
adjusted pH.
21. Advantages of Tablets
1. Accurate stable dose with high precision and uniformity.
2. Easy to carry, handle and use.
3. Attractive, convenient and elegant in appearance.
4. Physically, chemically and microbiologically more stable dosage form.
5. High speed production, bulk production could be attained and hence lowers the
cost.
6. Packaging and shipping is easy and of low cost.
7. Unpleasant taste and odour can be masked.
8. Wide range of tablet types offering range of release rates and duration of clinical
effects.
9. Can offer release of active substance at a particular site.
10. Combination of more than one therapeutic agent.
11. Tablet can be divided offering different doses for use.
12. All classes of therapeutic agents with exception of proteins can be formulated in
tablet form
13. Easy to be identified due to differences in shapes and colours.
22. Disadvantages
1. Increased product loss due to the long series of unit process.
2. Absorption is dependent in physiological factors giving interpatient
variations.
3. Poor compressibility of certain therapeutic agents.
4. Difficulty in administration to certain groups like children but swallow
problems can be overcome by using effervescent tablets .
5. Agents that are liquid in nature is difficult to be formulated as tablets.
6. Oxygen sensitive agent may require special measures.
7. Drugs having poor wetting properties, slow dissolution profile and high
optimal gastrointestinal absorption are difficult to be formulated as
tablets.
23. Characteristics required
1. Deliver the correct amount of drug in a proper form at or over proper time.
2. Elegant free from defects like cracks, chips, contamination, discolouration …etc.
3. Maintain its chemical and physical integrity over time.
4. should be capable to maintain the chemical and physical properties of the therapeutic agent.
5. Withstand the rigorous mechanical shocks during manufacturing, shipping and storage.
6. Release medicaments in the body in predictable and reproducible manner.
25. Desired Properties of API
1. Purity :In accordance with the respective pharmacopoeia.
2. High stability
3. Compatibility with excipients: e.g primary amine and lactose.
4. Optimum bulk powder properties to have good flow, prevent segregation and to
optimize the tablet size.
5. Uniformity of particle size distribution to obtain uniformity in content,
uniformity in weight, disintegration time, friability, drying rate uniformity,
enhanced powder flow, good compression, regular dissolution and
bioavailability. fine particles increase surface area hence increases the surface
energy giving good compressibility.
6. Spherical shape provides good flow. Irregular particle shape may lead to
interlocking
26. Desired Properties of API- contd
7. Good powder flow: measured using angle of repose and can be improved by
addition of glidants, addition of fines, using wet granulation and increase the
density.
8. Optimum moisture content: lack of moisture in brittle tablets. increased
moisture affects uniformity of content, make sticking and picking
• Moisture can be controlled by;
Use of anhydrous salt
Use of nonaquous solvent.
Optimum drying time.
Addition of adsorbent like Magnesium oxide.
9. Good compressibility. This is an intrinsic nature of elasticity, plasticity and brittle
fracture of particles upon compression.
10. Absence of static charges and if any can be removed by granulation, addition of
diluent or lubricant or coating by colloidal silica.
11. Good organoleptic properties.
28. Functions of excipients.
•Operation run
satisfactory.
•Ensure that tablets of
specified quality are
prepared.
• Impart weight, accuracy and volume.
• Improve solubility
• Increase stability.
• Enhance bioavailability.
• Modify drug release.
• Assist product identification.
• Increase patient acceptability.
• Facilitate dosage form design.
29. Diluents / Fillers
• Normally tablet size is more than 50 mg and diameter above 2-3 mm. Fillers
increase the bulk of the powder to produce the desired size.
• Secondary functions are to improve the powder cohesion, to allow direct
compression, to enhance powder flow and to adjust the weight as per die
capacity.
• It constitutes 5 – 80% of the tablet weight.
30. General properties of diluents
• Chemically inert and of no microbiological load.
• No-hygroscopic.
• Compatible to the manufacturing process and other tablet
constituents.
• Good and consistent biochemical properties.
• Fair compactibility and dilution capacity.
• Acceptable taste and color.
• Low cost.
31. Types of diluents
I. Organic:
Starch, sugars, cellulose derivatives.
II. Inorganic:
Calcium phosphates.
III. Co- processed diluents.
combining two or more materials by appropriate process.
32. Starch
• It is polysaccharide composed of amylose and amylopectin.
• Pregelatinised grade which provide free flow of powder.
• Used as a diluent, binder and disintegrant…… details later.
33. Lactose – different particle size, crystal form and properties.
Property Monohydrate Anhydrous Spray dried
Moisture content 5% Pick up moisture at high RH Depend on the extend of
drying
Flow Poor Poor Free flow
Compressibility Wet granulation Directly compressible Directly compressible
Maillard reaction
(Brownian)
Take place In the presence of
moisture
In presence of excess
moisture
Cost Cheap Cheap Expensive
Solubility Soluble Soluble Soluble
Disintegrant Needed No need No need
34. Mannitol
• Generally used for chewable tablets due to inherent sweetness
and negative heat of solution properties.
• Unlike sucrose it is free from grittiness.
• Most expensive sugar.
• It requires high lubricant content.
• Often combined with its isomer sorbitol.
35. Celluloses – Microcrystalline cellulose MCC
• Highly compressible and widely used in direct compression.
• Hard tablet at low compression can be obtained.
• Fair flow.
• Binding and disintegration properties.
• Commonly used grades are Avicel Ph101, Avicel Ph 102.
36. Calcium Phosphates -
• Excellent compressibility and flow.
• Bulk density is higher.
• Hard tablets are obtained.
• Non – hygroscopic and inexpensive.
• Because of its alkalinity in moisture it is a source of instability in acidic products.
• Interact with some API such as Tetracycline.
• Dibasic calcium phosphate, dicalcium phosphate, calcium hydrogen phosph dehydrate.
• Tribasic calcium phosph, tricalcium phosph, tricalcium orthophosphate.
37. Binders – Adhesives
• Added to cause particles of drug and other excipients to cohere
into a granular form of required mechanical strength.
• It can be termed as granulating agent.
• Generally binders are polymeric in nature.
39. •List of Direct Compression Binders
o MCC ( Avicel PH 101 )
o Silicified microcrystalline cellulose.
o Partialy Pregelatinized Starch.
o Low density starch.
o DC lactose anhydrous.
o DC- Dibasic calcium phosphate dihydrate.
40. Characters of Commonly Used Binders
Binder Concentration Characters
Starch paste 5 – 25% w/w Freshly prepared paste.
Pregelatinized
starch
5 – 10% w/w
Direct compression
Starch that processed chemically and mechanically to rupture all or part o
granules in the presence of water then dried.
Partially & Fully
PGS
5 – 75% w/w
Wet granulation
Obtained from potato, maize or rice starch. Used as diluent, binder,
disintegrant and flow aid. Can use cold water.
HPMC 2 – 5% w/w Can be used in either wet or dry granulation.
PVP 0.5 – 5% w/w added to powder blend in dry state then water is added during
granulation.
PEG 10 – 15% w/w Used as meltable binder. Anhydrous granulating agent. I improve plasticity
of other binders. Prolong disintegration time.
41. methods of adding the binder
• As a dry powder mixed with the other ingredients before wetting.
• As a solution which is used as agglomerating liquid during wet
agglomeration.
• As dry powder which is mixed with other ingredients before
compaction. ( dry binder).
42. Lubricants
Lubricants are materials that acts at the interface between the surface of the tablet
and the face of die preventing the adhesion of the tablet material to the surface of the
die and punch reducing the friction and facilitate ejection of the tablet from the die
cavity.
Critical factors for optimizing lubricant function:
oConcentration of lubricant. Inadequate concentration result in tablet with pitted
surface and inability of tablet to detach from the die. High concentration result in
prolonged disintegration. Insoluble lubricant can be added at the final mixing stage
before compression.
oStage and way of mixing. Mixing of lubricant with the disintegrant together lead to
formation of lubricant film around the disintegrant which reduces the wettability and
water uptake by the disintegrant resulting in disintegration failure.
oIntensity and duration of mixing. Over mixing or high intensity of mixing result
disintegration and dissolution failure.
oLubricant Particle Size. Smaller particle size enhance lubricant efficiency.
44. Glidants
They are water insoluble materials of a very fine particle size enhancing the
powder flow properties of the granules within the hopper into the tablet die by
reducing the friction due to their ability of particles to be located within the
spaces between the granules.
As they are almost hydrophobic , increase in concentration will reduce the
disintegration and dissolution time.
Talc asbestos-free ( hydrated Magnesium silicate) is insoluble but not
hydrophobic 5 – 30% but its use was restricted because it will result in granuloma
if inhaled.
Colloidal Silicon Dioxide (Aerosil) 0.1 -0.5% w/w was used due to its hydrophobic
properties and fine particle size less than 15nm.
45. • Adsorbents:
If liquid or semisolid is to be incorporated in the solid powder and the powder is
required to be attained solid, and adsorbent is required to is included in the formula
(e.g. magnesium oxide/ carbonate, kaolin/bentonite.
• Sweeting agents / Flavours:
to improve the taste and odour of the chewable tablets. Mannitol, lactose, sucrose
and dextrose – saccharin, cyclamate, aspartame.
• Colours:
Can be used for the powder or for the coating material to give elegant appearance,
to serve the manufacturer and patient in drug identification. e.g. iron oxide,
carentoids, anthrocyanins.
• Surface active agents:
To improve the wetting properties of hydrophobic tablets .
To increase the aqueous solubility of poorly soluble drugs( sodium lauryl sulphate)
46. Disintegrants
• Bioavailability of a drug depends in its
absorption which is affected by its dissolution
and permeability across the GIT membrane.
• The rate of dissolution is greatly influenced by
the rate of disintegration.
• Disintegration must occur within the
specifications defined by the pharmacopoeia (
generally 15 minutes ).
• Disintegrant was added to the formulation to
achieve this specification.
47. Mechanism of action of disintegrants
∆Increase the porosity and wettability of the tablet matrix enabling the GIT fluids to
penetrate and thereby enable tablet breakdown to occur. Concentration 5 – 20%w/w.
- Starch, corn and potato starches.
- MCC Avicel 101 & Avicel 102. 10 -20% w/w.
- Sodium starch glycolate 5% w/w.
∆Swelling of disintegrant in the presence of the aqueous fluid leading to tablet
disintegration due to increase in the internal pressure within the tablet matrix.
- Sodium starch glycolate
- Croscarmellose sodium 0.5-5% w/w.
- Crospovidone 2 – 5% w/w.
- Pregelatinized starch 5% w/w.
∆Liberation of gas – Effervescent tablets.
48. Mode of addition of disintegrant
• Intragranular addition.
• Extragranular addition.
• 50% intragranular and 50% extragranular.
49. Factors affecting disintegration
1. Effect of fillers:
soluble fillers increase the viscosity of the penetrating fluid which tend to reduce
the effect of the swollen disintegrating agent which tend to dissolve rather than
disintegrate. Insoluble fillers disintegrate more rapidly.
2. Effect of lubricants:
as lubricants are hydrophobic, they inhibit wetting and consequently disintegration of tablets.
Sod. starch glycolate remains unaffected as disintegrant.
3. Effect of binders:
Increase in the concentration of the binder increases the disintegration time.
4. Effect of Surfactants:
The speed of water penetration is increased by addition of surfactants.
50. Excipient Function
Diluent ( filler) Required bulk of tablet
Binder Provide necessary bonding to form granules
Disintegrant To bring disintegration within the specified time.
Lubricant To reduce friction in the die and ejection of tablet from the die cavity.
Antiadherent To prevent sticking of powder to the faces of punch and die.
Glidant Promote powder flow.
Wetting agent To aid disintegration
Buffer To improve stability and bioavailability.
Antioxidant to attain stability
Chelating agent Complex with heavy metals to prevent autooxidation.
Preservative To prevent growth of microorganism
Color Disguise off color drugs, product identification and more elegant colour
Flavour To improve odour and taste
52. Granulation
• Advantages of use of granules:
• Prevention of segregation of powder components during the tableting
process.
• Enhancement of flow properties.
• Enhancement of compressibility.
• Lower incidence of dust production.
55. Wet granulation stage 1, Mixing
• Drug and excipients excluding lubricants.
• Mixing time and speed should be enough to produce
homogeneous mixture.
• Planetary bowel mixer.
• Rotating drum mixer.
• High-speed mixers.
• Ribbon / trough mixers.
56. Planetary bowel mixer.
• The mixing shaft rotate around the bowel and
around itself.
• Planetary like movement.
• Material used is stainless steel
57. Rotating drum mixer. ( double cone)
• The mixing shaft rotate and hence the drum is
rotated.
• Material used is stainless steel
58. Ribbon / trough mixer
• Mixing blades.
• Material used is stainless steel
59. Rapid mixer granulator
• Rapid mixer granulator is a
mixing unit with a bottom entry
agitator and side mounted
chopper for granulation. Can be
used for dry blending, wet mixing
and granulation. The principle is
agitation of the content at
moderate speed and then running
the cutting blade at high speed.
• Dry mixing 3-5 min, wet mass 5-
10 min then 5-10 min to produce
0.5 – 1.5 mm granules.
60. Wet granulation stage 2, Wet granules formation
• Fluid simultaneously incorporated in the powder mix. Granulation fluids are
water, isopropanol, ethanol or mixture.
• The binder is either incorporated in the solid state within the powder mix or
dissolved in the granulation fluid.
• Wet Granulation Techniques
A- Oscillating granulator
B- Fluidized bed granulation
C- Extrusion spheronization
D- Rapid mixture granulator RMG
E. Spray drying granulation.
61. Oscillating granulator
• Low sheer is used,
• The binder in the granulating
fluid is added whilst
maintaining mixing.
• The wetted powder mass is
then passed into an oscillating
granulator which forces the
powder mass through a metal
screen under the action of an
oscillatory stress.
62. Fluidized bed
granulator
• The powder is suspended by vertical
flow of air from the bottom of the
granulator.
• The granulation fluid is sprayed on
the powder from the top of the
granulator.
• Tangential air flow provides circular
powder suspension.
• Air applied with controlled
temperature.
63. Extruder
• Premixed powder to which the granulation fluid
being added is placed into the barrel of the
extruder via hopper.
• In the barrel the wet mass moves horizontally
via single or twin screws from the hopper end
by a turning motion.
• Passed through a perforated plate into lengths.
• The extruded strands should break to produce
granules of uniform particle size.
64. Rapid mixer granulator
• Rapid mixer granulator is a
mixing unit with a bottom entry
agitator and side mounted
chopper for granulation. Can be
used for dry blending, wet mixing
and granulation. The principle is
agitation of the content at
moderate speed and then running
the cutting blade at high speed.
• Dry mixing 3-5 min, wet mass 5-
10 min then 5-10 min to produce
0.5 – 1.5 mm granules.
65. Drying of the granules
1. Tray dryer: Traditional oven . Wet granules are placed horizontally in a shallow plates. Air entered the drier
warmed by heaters. Vacuum can be applied. Condensed water is collected and disposed.
2. FBD: often used in the industry and having the advantages of:
1. Excellent heat transfer and rapid in action.
2. Accurate control of the drying conditions.
And of limitation:
1. Attrition of granules.
2. Powder waste.
3. Development of static electricity .
3. Freeze drying, microwave dryer, spray dryer.
66. Milling of the granules ( Resizing)
• To produce the required particle size
and distribution to improve the flow of
powder into the die and its filling. The
granule size decreases as the tablet size
decreases.
• Size reduction methods includes:
• Oscillating granulator
using defined mesh.
• Quadro Comil
conical chamber containing defined
mesh . Granules pass through the
screen in a centrifugal manner by the
action of rotating impeller.
67. Incorporating the lubricant
• Mixing the lubricant with the dried granules usually takes place in the
same mixing equipment used in the first stage.
• Noted that the time of mixing and the shear rate are crucial.
68. Granules formation
• Particle –particle interactions facilitated by
the formation of liquid bridges.
• Pendular state.
• Funicular state
• Capillary state
• Over-wetted state
70. Granules formation - contd
• Particle – Particle interactions facilitated by the formation of solid bridge.
• They are formed from the polymeric binder following drying.
• These bridges contribute to the mechanical properties of the resulting granules.
• Crystallization of the binder followed by crystallization of the water soluble drug
may affect directly the quality of produced tablets.( sugars)
71. Advantages of wet granulation
• Reduce segregation during process and storage leading to intra and inter-
batches variations.
• Useful for tablets contain low concentration of therapeutic agent.
• Employs conventional excipients.
• Most plants had been built around wet granulation.
• Tablets produced have good mechanical strength and hence can withstand
coating and packing procedures.
72. Disadvantages of wet granulation
• Several process steps.
• Presence of solvent lead to:
• In materials having susceptibility to Hydrolysis.
• Soluble drugs may crystallize during drying.
• Heat to remove the solvent make the process expensive.
• Thermally labile therapeutic agents may undergo degradation.
• Issues regarding the use of alcohol if used.
73. DRY GRANULATION
For thermolabile material
For materials that can be affected by solvent
Ingredient having enough cohesive properties.
75. Dry Granulation - Slugging
•Slugging is the process of compressing dry powder by tablet
press having large die cavity, flat-faced punches and high
compression pressure.
•Slugs are then undergo size reduction by screening and milling.
76. Dry Granulation – Roller Compaction
•Slugging is the process of compressing dry powder by tablet
press having large die cavity, flat-faced punches and high
compression pressure.
•Slugs are then undergo size reduction by screening and milling.
77. Chilsonator
Dry granulation – Compactor –
Chilsonator
• The powder was compressed between
the two rolls which are connected to a
pressure regulator.
• Slugs pass down to granulator then the
particles screened.
• Fine powders are hen recycled.
• High pressure was used.
79. Mechanism of granules formation in dry granulation
• Electrostatic forces.
Initial cohesive interaction between particles.
• Van der Waals interactions
Van der Waals forces increases as the distance between the particles
decreases.
• Melting of components within the powder mix
Due to partial melting of excipients upon cooling solidification occur
resulting in increased interactions between adjacent particles.
80. Advantage of dry granulation
• No need for special excipients
• No heat , no solvent
• No change in the morphology of ingredients.
81. Disadvantage of dry granulation
• Soft tablet incapable for further processing like coating.
• Dust generation and powder loss.
• Segregation of components may occur post mixing.
• Special equipment required.
• Problems with powder flow.
82. Direct compression
• Mixing and subsequent compression.
• Interactions of particles are similar to dry granulation.
• To obtain same and uniform particle size of ingredients, this may
require milling.
• Qudro Comil
• High energy mill
• Fitzmill
• Mixing in the same mixers as wet granulation.
86. Excipients – Direct Compression
• Specific grades are required ( spray dried) to achieve certain particle size
distribution and flow properties.
Diluent - Spray dried lactose
- Encompress calcium phosphate.
- Spray dried mannitol
- sorbitol
- MCC Avicel PH- 102
Compression aid Avicel PH- 102
Disintegrant - PGS
- Sodium starch glycolate ( Primogel)
- Croscarmellose sodium
- Crospovidone - polyplasdone
Lubricants - Stearates
Glidants - Talc
- Colloidal silicon dioxide
87. Advantages of DC
• Fewer processing steps and cost effective.
• No use of water or solvent, no heat so produce more stable product
and lessens the cost.
• Lubricant is incorporated in the same vessel.
88. Disadvantage of DC
1. Specialist more expensive excipients.
2. Similar particle size and density for the excipients and the
therapeutic agent are required to minimize segregation.
3. Powder flow within the tableting machine.
4. Tablets produced are soft making it difficult for further
processing.
5. If the API is more than 10%, it will affect compressibility.
6. Colourants could not be used.
7. Dust and waste.
91. Stages of compression
• Stage1 : Filling the die with the granules / powder:
• The powder or granules are fed from the hopper of machine into the die filling
the space between the lower and upper punches.
• The space is determined by the position of the lower punch which can be altered
to increase or decrease the tablet size.
92. Stages of compression
• Stage2 : compression ofthe granules / powder bed:
• Retraction of the shoe.
• Upper punch descend and compress the powder.
93. Stages of compression
• Stage 3 : Tablet ejection:
• Upper punch is elevated to its original position.
• The lower punch moves upwards until it flush with the die plate.
• The shoe moved across the die plate pushing the tablet from the lower press.
• The lower punch returns to its original position to start new cycle.
94. Types of Tablet Presss
• Single-Punch
tableting
Machines
• This tablet press
composed of
only one set of
punches and die.
• Used in pilot-
scale
manufacturing
and in R&D or in
dry granulation
(slugging)
• Speed is up to
200 tablets per
minute.
97. Rotary Tablet Press
• For large scale , produce up to 10,000 tablet per minute.
• Have up to 60 sets of punches and dies.
• Dies table rotate in a circular motion.
• Lower and upper Punches being held by the turrets are lowered and elevated by an upper and
lower rollers.
• The powder l granules are fed from the hopper on the upper surface of the die table. Then
transported by a feed frame into the die, where they are subsequently compressed by the
simultaneous movement of the upper and lower punches.
• The tablets are removed from the rotating die table into a chute from which they are collected.
101. Compression Cycle
1. Powder or granules fed to the hopper, emptied into the feed frame by gravity.
2. The interconnected compartments of the feed frame spread the powder over
the area and fill the dies.
3. The pull down cam guide the lower punches downwards allowing dies overfill.
4. Punches pass over a weight-control cam, which reduces the fill into the dies to
the desired amount.
5. A wipe off blade at the end of the feed frame removes the excess.
6. The lower punches move over the lower compression roll while the upper
punches ride beneath the upper compression roll and enter into the dies while
the lower punches are raised to squeeze the powder within the die.( moment
of compression)
7. The upper punches are withdrawn following the upper cam, the lower
punches ride up the lower cam bringing the tablets up the surface of the dies.
8. The tablet strike the sweep off blade in front of the feed frame and slide it
down the chute into the container.
102. Relationship between Stress and Strain
Elastic region:
If the powder properties is elastic , will result in delamination and tablet failure.
Stress required for the manufacturing of tablet should be greater than that
required for elastic deformation.
Plastic region:
Due to the movement of the molecules in the direction of stress, irreversible
deformation occurs. Components undergo plastic deformation, yield a successful
compression.
Fragmentation :
Applying the ultimate tensile strength, particles will fracture. Further stress will
result in more particle fractures so, increasing the surface area allowing more sites
for particle-particle interaction.
103. Behavior of the powder bed during compression
• Stage 1:
Rearrangement of the powder bed upon application of stress, minimize
the free space between the particles.
• Stage 2 :
Deformation of the powder under applied stress.(plastic deformation
and fragmentation
• Stage 3 :
Bonding of the compressed powder by inter-particle bonding resulting
in intact tablet. Bonding by adsorption ( van der Waals forces) and by
diffusion ( increased molecular mobility) .
104. Compression &
time
1- Dwell time :
time at maximum
2- consolidation time:
Time to maximum force.
3- Ejection time:
time during which ejection
occur.
4- residence time:
time during which the formed
compact is within the die,
5- contact time:
time for compression and
decompression excluding
ejection time
105. Auxiliary equipment
• Mechanical feeder
• To force granules into the die cavity.
To minimize weight variation and obtain uniformity in content.
• Tablet weight monitoring device
Monitoring force at each compression station by electronic strain
gauge technology.
• Tablet deduster :
To remove the excess powder on the surface of tablets.
107. •The upper or the lower segment of the
table separates horizontally, either partially
or completely.
•Causes may be either due to the
formulation or due to machine.
Reason:
Air entrapped in
compact during
compression and
subsequent
expansion on
ejection from the
die or handling.
108. Causes Remedies
Large amount of fines in the granulation. Remove fines through 100 -200 mesh
screen.
Too dry or very low moisture leading to
loss of binding action
Moist the granules or add hygroscopic
e.g sorbitol, PEG 4000.
Not thoroughly dried granules. Dry the granules properly
Insufficient or improper binder Increase or change binder.
Insufficient or improper lubricant Increase or change lubricant
Granular mass too cold to compress Compress at room temperature.
109. Causes Remedies
Poorly finished dies. Polish dies properly
Deep concave punches or beveled edge
faces of punches
Use flat punches
Lower punch remain below the level of
the die plate during ejection
Make proper setting
Incorrect adjustment of sweep-off blade Adjustment of ejection blade.
High turret speed Increase dwell time
110. •Tablet may undergo separation into two or
more horizontal layers.
•Causes may be either due to the
formulation or due to machine.
Reason:
Air entrapped in
compact during
compression and
subsequent release
on ejection. The
condition exaggerated
by higher speed of
turret.
111. Causes Remedies
Oily or waxy materials granules - Modify mixing process
- Add adsorbent or absorbent
Too much of hydrophobic lubricant e.g
Magnesium stearate
- Decrease the amount or change the
lubricant.
Lamination due to machine causes and its remedies
Rapid relaxation of the peripheral regions of
the tablet, on ejection from a die
- Use tapered die , upper part of the die bore
has an outward taper of 3 -5˚
Rapid decompression - Use precompression step .
- Reduce turret speed and reduce the final
compression pressure.
112. •Small cracks on the centre of the upper or
lower surfaces.
•Causes may be either due to the
formulation or due to machine.
Reason:
Rapid expansion of
tablet especially when
deep concave punches
are used.
113. Causes Remedies
Large size of granules - Reduce granules size
- Add fines
Too dry granules - Moisten the granules properly
- Add proper amount of binder
Tablets expand - Improve granulation
- Add dry binder
Too cold granulation Compress at room temperature.
Cracking due to machine causes and its remedies
Tablet expand on ejection due to air entrapped - Use tapered die , upper part of the die bore
has an outward taper of 3 -5˚
Deep cavities cause cracking while removing
tablets
- Use less concave punches.
- Use gentle take-off ejection device..
114. •Tablet material adhere to the punch.
•Causes may be either due to the
formulation or due to machine.
Reason:
Air entrapped in
compact during
compression and
subsequent release
on ejection. The
condition exaggerated
by higher speed of
turret.
115. Causes Remedies
Moist granules Determine optimum time for drying
Insufficient or improper lubricant - Increase lubrication
- Use colloidal silica as polishing
Low melting point of substance Use high melting point materials
Too warm granules Cool the system
Excess binder Reduce or change the binder
116. Causes Remedies
Rough or scratched surface of punch Polish punch face properly
Imposing or engraving letters Design letters as large as possible
Too deep dividing line or bevels Reduce depth and sharpness
Insufficient pressure Optimize the pressure
117. •Tablet material adhere to the die faces. Filming is a slow form of
sticking due to excess moisture.
•Causes may be either due to the formulation or due to
machine.
Reason:
Improperly dried or
improperly lubricated
granules
118. Causes Remedies
Moist granules, hygroscopic material Determine optimum time for drying,
control humidity
Insufficient or improper lubricant - Increase lubrication
- Use colloidal silica as polishing
Too much binder Decrease or change the binder
Oily or waxy material Modify mixing process, add adsorbent
Too soft or weak granules Optimize binding , change granulation
technique.
119. Causes Remedies
Rough or scratched surface of die Polish die face properly
Die design Use tapering dies
Too fast speed Reduce speed
Insufficient pressure Optimize the pressure
120. •The tablet adhere or tear in the die. A film
is formed un the die and ejection is
hindered. Tablet edges are cracked.
•Causes may be either due to the
formulation or due to machine.
Reason:
Excessive moisture,
lack of lubricant,
worn dies
121. Causes Remedies
Too moist granules expanded around the
lower punch
Optimum drying
Insufficient or improper binder Increase of change lubricant
Too large granules Reduce the size or add fines or add
more lubricant
Too hard granules for the lubricant to be
effective
Reduce granular size or modify the
granulation method
Too abrasive granules and cutting into
the die
Reduce granular size
Granular mass too warm stick to the die Reduce temperature
122. Causes Remedies
Poorly finished dies. Polish dies properly
Rough dies due to abrasion or corrosion Change dies
Undersized dies Use proper die size
Too much pressure Reduce pressure or modify granulation
123. •Pit marks on the surface of the tablet
•Corrected by polishing the punch surface
and increasing the lubricant, its time and
rate of mixing.
Reason:
Rough surface of
the punch or
insufficient
lubricant
124. •Sticking of the tablet to the die and do not
eject properly.
•Causes and remidies are the same as
chipping.
Reason:
Excessive moisture,
insufficient
lubrication or use
of worn die
125. •Uneven distribution of colour with black or
light spots in the surface.
•May be due to the formulation or the
tableting machine. Reason:
Spotted colouration
on the surface of
the tablet.
126. Causes Remedies
A coloured drug used with white excipients. Use appropriate colouring agent
A dye migrate to the surface of the granules during
drying
- Change the solvent & binder
- Reduce the drying temp
- Use smaller particle size
Improperly mixed dye - Reduce size and mix properly
Improper mixing of coloured binder Incorporate dry color during blending then
add dry binder, mix then add the
granulating fluid.
Waxes and oils of machine parts lubrication - Check the seals
Dust - Clean and clear the environment
127. • It takes place in only those punches
having engraving.
At the moment of compression, the tablet receives the imprint, the upper or
lower punch rotate freely and travelling a distance which may result another
contact with the tablet resulting in double impression.
Revise setting of machine and tie the punch by tooling key.
Use punches with male and female anti-turning lock to prevent rotation.
Reason:
Free rotation of either
the lower or upper
punches during
ejection of tablet.
129. Tablet Coating
• PURPOSES OF TABLET COATING
1. To prevent degradation in the
stomach – ( enteric coating )
2. To prevent drug induced irritation at
the stomach-( NSAI)
3. To provide controlled release of the
drug throughout the GIT.
4. To target drug release at specific site
in the GIT. ( colon)
5. To mask the taste of the drug.
6. To improve the appearance of
tablet.
7. To protect the tablet – shelf-life &
stability
• TYPES OF TABLET COATING PROCESS
1. Sugar Coating
2. Film Coating.
3. Press Coating
• TYPES OF COATING EQUIPMENTS
1. Standard coating pan
2. Perforated coating pan
3. Fluidized bed ( air suspension)
coaters.
130. Sugar coating
• Coloured or uncoloured of
sucrose - based layer around
the tablet.
• Improve the appearance and
mask the taste.
• Insulate the tablet.
• Permit imprint.
• Dramatically decreased
practice due to advantages of
film coating.
Conventional Pan
131. Process of sugar coating
• Stages of process:
1. Sealing of tablet cores.
2. Sub-coating
3. Smoothing
4. Colouring
5. Polishing
6. Printing
• General description of the process:
1. Tablets are placed in the coating pan and agitated.
2. The coating solution is sprayed on the surface of
the tablets.
3. Warm air is passed over the tablets to facilitate
removal of the solvent.
4. When solvent has evaporated, the tablets will be
coated with the solid components of the coating
solution.
132. 1-Sealing of tablet cores.
• An insoluble impermeable polymer solution is applied to seal
the tablet against entry of water.
1. Shellac
2. Cellulose acetate phthalate
3. Polyvinylacetate phthalate
4. Hydroxypropylmethyl cellulose
133. 2-Subcoating
Sub-coating solution
Gelatin 6% W/W 3.3 % W/W
Acacia 8 7.7
Sucrose 45 55.3
Distilled
water
To 100 To 100
Sub-coating suspension
Sucrose 40% W/W
Calcium
carbonate
20
Talc 12
Gum acacia 2
Titanium dioxide 1
Distilled water 25
1. Applying the gum based solution followed by sucrose
based powder then drying.
2. Application of a suspension of powder in gum-sucrose
solution
3. Powders as Calcium carbonate or Talc.
134. 3- Smoothing
• Rough surface can be smoothened by application of few coating
layers of simple syrup.
• The simple syrup may contain starch, acacia, gelatin and opacifier.
135. 4- Colouring
• Application of several layers of colour solution in 60 – 70%
sucrose syrup.
• Colours should be approved by the regulatory authority.
• Predispersed lake ( pigment) is superior because:
1. The colour is water insoluble.
2. It is opaque.
3. Maintenance of batch to batch colour.
4. Reduction in the overall process time.
5. Reduction in the thickness of the colour coating layer.
136. 5- Polishing
• Commonly used method is an application of organic solvent to
get suspension or solution of waxes.
• Carnauba wax
• Beeswax
• An emulsion may be used and stabilized by acceptable
surfactant.
• Other methods involves the use wax-lines pan and use finely
powdered wax application.
• Mineral oil application.
137. 6- Printing
• Why sugar coated tablets requires printing for and not
other method for identification?
• Edible pharmaceutical ink formulation:
• Shellac
• Alcohol
• Pigment
• Lecithen
• Antifoam
• Organic solvent
138. Film Coating
• A deposition of a thin film layer of polymer or mixture of polymers around the
conventional tablets core.
• Polymers that are used in film coating which dissolve in the stomach to enable
disintegration and dissolution :
• Hydroxypropylmethyl cellulose.HPMC
• Hydroxypropyl cellulose HPC
• Eudragit E 100
• Target drug release film coated tablets are coated by insoluble
• Ethylcellulose.
• Eudragit RS & RL
139. Comparison between Sugar & Film coating
Features Sugar coating Film coating
Appearance Rounded with degree of
polish
Retains contour of the original
tablet – not shiny
Weight increase 30 – 50 % 2 – 3 %
Logo or break-lines Not possible Possible
Other dosage form Of no industrial
importance
possible - multiparticulates
Stages of process Multistage process Single
Batch coating time 8 hours 2 hours
Functional coating Generally not practical Controlled release
140. Advantages of Film coating
• Elegance and glossy appearance.
• Maintain the logo and break line.
• Improve mechanical strength an integrity and improve
resistance for handling and shipping.
• Flexibility in types of formulation.
• Minimal weight increase.
• Less time consuming.
• Minimize dust.
• Automated equipment are used.
• Single process and not requires excessive training.
141. Formulation of the coating fluid
Polymer ( may be enteric or nonenteric)
Plasticizer
Colourant
Opaquant – extender
Solvent
142. Polymers for Enteric-coating
Cellulose acetate phthalate / cellulose acetate butyrate
Hydroxypropylmethyl cellulose succinate.
Methacrylic acid co-polymers [ Eudragit®]
- Eudragit L-100 dissolve at pH > 5.5
- Eudragit S-100 use for target organ drug release ( colon)
dissolve at pH > 7.
143. Polymers for Film-coating
Hydroxypropylmethyl cellulose.
Hydroxy propyl cellulose.
Edragit E100
Ethylcellulose: insoluble at all pH, drug released by diffusion and
subsequent partitioning into the gastrointestinal fluid. Needs placiticiser.
Eudragit RS and RL: insoluble used for delayed action.
Dissolve in the stomach , freely soluble in
the gastric fluid
144. Plasiticizer
- To increase the flexibility of the film.
- 1- 50% by weight of the coating solution.
- Polyols: glycerol, propylene glycol, polyethylenglycol.
- Organic esters: water insoluble e.g Diethylphthalate, dibutylphthalate, Acetyl
triethyl citrate, Acetyl tributyl citrate, tributyl citrate.
Water miscible as triethyl citrate and glyceryl triacetate.
- Oils: they are water insoluble e.g castor oil, Acetylated monoglyceride,
Fractionated coconut oil.
145. Colourants
Powdered colourant should be micronized < 10 microns.
Inorganic: iron oxide.
Natural, anthocyanins, carotenoids.
Magenta red dye, mica
146. Opaquant-extender
They are very fine powder of inorganic material used to provide more
pastel colours and increase film coverage.
- Titanium dioxide
- Silicate ( talc and aluminum silicates)
- Magnesium Carbonate.
- Magnesium Oxide.
- Aluminum hydroxides.
147. Solvents
They are used to dissolve or disperse the polymers and the other
additives and convey them to tablet surface.
Solvent requirements:
1. Easily dissolve or disperse the polymer system.
2. Easily disperse the other additives.
3. Should not be extremely viscous when mixed with the polymer.
4. Colourelss, odourless, tasteless, inexpensive, noniflammable, nontoxic, inert.
5. Rapid drying rate
6. No environmental pollution.
Water, ethanol, methanol, isopropanol, chloroform, acetone, methylene chloride………..
148. 3. Press Coating
Compaction of the coating material around the tablet core.
Other limited coating processes:
- Compressed coating.
- Electrostatic coating.
- Dip coating.
- Vacuum film coating.
149. Tablet Coating Equipment – Standard Coating Pan
• 60 – 80 inches circular metal pan mounted angularly on a stand.
• It rotates horizontally around its axis by a motor.
• Heated air is directed to the face of the tablet bed and exhausted by
means of a duct located at the front of the pan..
• Coating solution applied by spraying onto the rotating tablet bed.
150. Tablet Coating Equipment – Pellegrini Coating Pan
• Has a baffled pan and diffuser that distribute the drying air uniformly
over the tablet bed surface.
• Use an atomized spray system.
151.
152.
153. Suitable for pellets, granules. Recommended for enteric coating and
sustained release. Not suitable for tablets
154. Factors Controlling the efficiency of the coating Process
• Temperature and solvent vapor pressure directly influence the evaporation rate and the process timing.
• Fluidized air volume within the chamber affect the velocity of the coating fluid droplets and their pattern.
• If the relative humidity within the chamber is high, evaporative cooling may occur resulting in lowering the
temperature below the dew point resulting in condensation of water on the tablet surface.
• Excessive spray rate results in poor adhesion of the coat to the tablet surface. Avoid droplet aggregation.
• Increased viscosity affects the atomization process.
155. Coating Process Parameters
• Air capacity value represents the quantity of solvent that can be removed by the quantity and temperature of
air flowing and the quantity of water that the inlet air contains.
• Thickness and viscosity of the fluid influence the rate of drying
• Increase on the surface area of tablets increases as the tablet size decreases. Resulting in more cycles
required to complete the process.
• Equipment coating efficiency = net increase in the coated tablet weight × 100
weight of nonvolatile coating fluid applied
Ideally 90% - 95%. - For sugar coating it is 60%.
156. Problems and remedies in tablet coating
1- Blistering
2- Chipping
3-Cratering
4- Picking
5- Roughness ( pitting)
6- Blooming
7- Blushing
8- Colour variation
9- Infilling
10-Orange peel (roughness)
11-Cracking (splitting)
12- Poor adhesion of the film to tablet
13- Abrasion
157. Defect : Blistering
Description : detachment of the film from the substrate forming a blister
Reasons : entrapment of gases underneath the film due to overheating.
Causes Remedies
Effect of temperature on he strength,
elasticity and adhesion of the film
Use mild drying conditions
Defect : Chipping
Description : film becomes chipped and dented usually at the edges.
Reasons : decreased fluidizing air or high speed of rotation.
Causes Remedies
High degree of attrition Increase hardness, use high
molecular weight polymer.
158. Defect : Cratering
Description : volcanic like craters on the tablet surface
Reasons : the coating solution penetrate the surface causing local disintegration .
Causes Remedies
- high rate of coating fluid application
- Inefficient drying
Increase viscosity to decrease the rate.
Optimize the drying conditions.
Defect : Picking
Description : isolated areas of the film being pulled away from the surface when
tablets sticks together.
Reasons : Over wetting the tablets then they stick together
Causes Remedies
- Inefficient drying Increase the inlet air temperature
- High rate of fluid application - Decrease the application rate by increasing viscosity
159. Defect : Pitting - roughness
Description : pits occur in the film without its disruption
Reasons : temperature used is more than the melting point of tablet material.
Causes Remedies
High temperature f the inlet air Modify the temperature of the inlet
air, not grater than the melting point
Defect : Blooming
Description :.dull tablets
Reasons : collection of low molecular weight of ingredients on the surface.
Causes Remedies
High concentration or low molecular weight
of plasticizer.
Decrease concn of plasticizer or use
that of high molecular weight
160. Defect : Blushing
Description : whitish or haziness speck in the film
Reasons : due to precipitation of the polymer due to high drying temperature
Causes Remedies
- High drying temperature
- Use of sorbitol which causes fall in the thermal
gelation of HPMC/cellulose ethers
- Decrease the drying temperature
- Avoid use of sorbitol with cellulose
esters
Defect : Colour Variations
Description :.inconsistent colour of tablets
Reasons : alternation of the frequency and duration of appearance of the tablets to the
spray zone or irregularity in the spray zone.
Causes Remedies
Improper mixing, uneven spray, insufficient
coating, migration of the dye into the tablet core
Appropriate mixing, mild drying
conditions, mask the effect of migration
161. Defect : Filling tablet markings
Description : filling the marks render them indistinct.
Reasons : inability of foam spray to break, droplet on the surface of marking.
Causes Remedies
- low drying temperature and low rotation speed.
- Excessive volume of coating fluid.
- Bubbles or foams during spray
- Deep marking.
- increase the drying temperature and rotation speed
- Adjust the spray nozzle.
Defect : Orange peel /roughness
Description :.rough surface and nonglossy like that of an orange surface.
Reasons : drying takes place before reaching the tablet surface.
Causes Remedies
- Rapid drying
- Highly viscous fluid
- Decrease temp and increase spray rate
- Decrease viscosity of coating fluid.
162. Defect : Crack formation / splitting
Description : cracks across the tablet crown or splitting at the edges
Reasons : internal strength exceeds the tensile strength of the film
Causes Remedies
- Inadequate plasticizer.
- The polymer has low resistance to tensile.
- Increase or change plasticizer
- Use appropriate polymer
Defect : Tablet abrasion
Description : damage of the tablet surface
Reasons : sheering stress resulted from the collisions of tablets with each other and with
the chamber walls.
Causes Remedies
Inappropriate tablet hardness, irregular tablet
shape, heavy tablet bed, excessive speed of
rotation, high rate of fluidizing air inlet.
Adjust hardness and change tablet shape.
Reduce the tablet load within the chamber.
Decrease the rotation speed and inlet air.
163. Defect : Poor adhesion of the coating to the tablet
Description : easily removable film
Reasons : poor adhesion of the coating fluid to the tablet.
Causes Remedies
- High RH within the chamber, while using
organic solvent system.
- High coating spray rate of the fluid.
- Low polymer concentration.
- Too low temperature.
- Air fluidization rate and rotation speed are too
low.
- Tablets have minimum required curvature.
- Adjust humidity.
- Appropriate rate of spray.
- Increase polymer concentration.
- Increase the temperature.
- Adjust the speed of rotation and the
rate of air inlet.
- Increase curvature of tablet faces.
164. IN PROCESS QUALITY CONTROL
TESTS
General appearance
Weight variations – mass uniformity*
Hardness – resistance to crushing of uncoated tablets*
Friability*
Disintegration*
Dissolution*
Uniformity in content*
Crushing strength of coated tablets
Adhesion
Stability studies
165. General appearance
• Control of tablet to tablet uniformity and batch
to batch uniformity.
Shape & Size:
- Thickness measured using the Vernier and
variation should not exceed ±5%.
- Diameter of tablet.
- Unique identifying marking.
Organoleptic properties:
- Colour may be measured using photometer
or spectrophotometry.
- Odour may be characteristic in some cases
as vitamins but usually presence of odour
may be due to the film or stability problem.
- Pleasant taste may be desired for chewable
tablet – unpleasant taste requires coating.
166. Weight variations – mass uniformity*
• (Ph.Eur. method 2.9.5) – BP 2016
• Weigh individually 20 units taken at random or, for single-
dose preparations presented in individual containers, the
contents of 20 units, and determine the average mass. Not
more than 2 of the individual masses deviate from the
average mass by more than the percentage deviation
shown in the Table. and none deviates by more than twice
that percentage
Uncoated and film
coated tablets
Average Mass Percentage Deviation
80 mg or less 10
More than 80 mg and less than 250 mg 7.5
250 mg or more 5
When the average mass is equal or below 40 mg , it is not submitted to mass uniformity test
but to the test for uniformity of content of single- dose preparations.
167. Resistance to Crushing – hardness testing
• Tablet should have certain hardness or mechanical strength to withstand the
upcoming processes but should not be too hard to fail disintegration and
dissolution and consequently bioavailability.
• OPERATING PROCEDURE
• Place the tablet between the jaws, taking into account, where applicable, the
shape, the break-mark and the inscription; for each measurement orient the
tablet in the same way with respect to the direction of application of the force.
Carry out the measurement on 10 tablets, taking care that all fragments of
tablets have been removed before each determination.
• This procedure does not apply when fully automated equipment is used.
Express the results as the mean, minimum and maximum values of the forces measured, all
expressed in newtons.
168. APPARATUS
The apparatus consists of 2
jaws facing each other, one
which moves towards the
other. The flat surfaces of the
jaws are perpendicular to the
direction of movement. The
crushing surfaces of the jaws
are flat and larger than the
zone of contact with the
tablet. The apparatus is
calibrated using a system
with a precision of 1 newton.
169. Friability Test
• For tablets with a unit mass equal to or less than 650 mg, take a sample of whole
tablets corresponding as near as possible to 6.5 g. For tablets with a unit mass of
more than 650 mg, take a sample of 10 whole tablets. The tablets are carefully
dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets
in the drum. Rotate the drum 100 times, and remove the tablets. Remove any
loose dust from the tablets as before, and accurately weigh.
• If obviously cracked, cleaved, or broken tablets are present in the tablet sample
after tumbling, the sample fails the test.
• If the results are difficult to interpret or if the weight loss is greater than the
targeted value, the test is repeated twice and the mean of the 3 tests determined. A
maximum loss of mass (obtained from a single test or from the mean of 3 tests)
not greater than 1.0 per cent is considered acceptable for most products. Dropping
distance is 6
inches.
Rotation
speed is 25
rpm.
170. Disintegration Test
Disintegration time is defined as the time required under a given set of conditions for a
group of tablet to disintegrate into particles which will pass through 10 mesh screen.
Procedure: Place 1 dosage unit in each of the 6 tubes of the basket and, if prescribed,
add a disc. Operate the apparatus using the specified medium, maintained at 37 ± 2 °C,
as the immersion fluid. At the end of the specified time, lift the basket from the fluid
and observe the dosage units: all of the dosage units have disintegrated completely. If 1
or 2 dosage units fail to disintegrate, repeat the test on 12 additional dosage units. The
requirements of the test are met if not less than 16 of the 18 being disintegrated .
Complete disintegration is defined as that state in which any residue of the unit, except
fragments of insoluble coating or capsule shell, remaining on the screen of the test apparatus
or adhering to the lower surface of the discs, if used, is a soft mass having no palpably firm
core.
171. Disintegration Apparatus
6 glass tubes of 3 inches length, opened at the top and 10
mesh screen at the bottom in a basket rack with 1-L beaker
container equipped with thermostat. The motor moves the
basket assembly up and down for a distance of 58 mm at
speed of 29 – 32 cycles per min. tablets should not be closer
more than 25 mm from the bottom and 15 mm from suface.
172. Disintegration conditions and interpretation
Type of tablet Medium Temperatu
re
Time limit
Uncoated tablets Water 37 ± 2 ˚C 15 min
Sugar coated Water, 0.1 N HCl if 1 or 2
failed
37 ± 2 ˚C 60 min
Film coated Water 37 ± 2 ˚C 30 min
Enteric coated • 0.1 N HCl +
• Phosphate buffer pH 6.8
• 37 ± 2 ˚C
• 37 ± 2 ˚C
• 1 hour +
• 1 hour = 2 hours
Dispersible /
Effervescent
Water 37 ± 2 ˚C 3 min
Buccal Water 37 ± 2 ˚C 4 hours
173. Dissolution
• Dissolution is the amount of drug substance
that goes into solution per unit time under standardized
condition of liquid / solid interface, temperature and solvent composition.
the dissolution rate is the rate of mass transfer from a solid surface into the
dissolution medium or solvent under standardized conditions of liquid/solid
interface, temperature and solvent composition per unit time.
There is a significant correlation between dissolution and bioavailability ( INIVC).
174. Dissolution test Apparatus
•BP -2016, There are four types of dissolution apparatus
1. Apparatus 1 : Basket Apparatus.
2. Apparatus 2 : Paddle Apparatus.
3. Apparatus 3 : Reciprocating Cylinder.
4. Apparatus 4 : Flow-through Cell.
175. Apparatus 1 : Basket apparatus
• A basket of 22 mesh screen fastened to a bottom of a
stainless shaft is immersed in one litre glass cylinder
of flanged top edges. The cylinder is placed in water
bath maintaining temperature 37˚C ±2.
• Basket is placed at a distance of 25 mm from the
bottom of the cylinder and the shaft is centered
within 2 mm from the vertical axis of the cylinder.
• One tablet is placed in the basket , the apparatus
turned on, then the basket rotate ( Stirring mode),
samples are taken every interval from the dissolution
medium for analysis to determine the amount of drug
being released.
176. Apparatus 2 : Paddle apparatus
• A paddle of a stainless composed of a blade fixed to a
shaft is immersed in one litre glass cylinder of flanged
top edges. The cylinder is placed in water bath
maintaining temperature 37˚C ±2.
• Paddle at a distance of 25 mm from the bottom of the
cylinder and the shaft is centered within 2 mm from
the vertical axis of the cylinder.
• One tablet is placed in the bottom of the cylinder and
not allowed to float , the apparatus turned on, then
the paddle rotate ( Stirring mode), samples are taken
every interval from the dissolution medium for
analysis to determine the amount of drug being
released.
