prof. emer. dr. klára pintye
TRANSCRIPT
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Prof. emer. Dr. Klára Pintye-Hódi
2019. 10. 29.
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• Tablets are solid preparations manufactured
by compression containing definite amount
of active ingredient of a single or multiple
dose.
• Tablets belong to the most commonly used
dosage forms due to their expansive use.
Definition
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Shape of tablets
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Some advantages of tablets
1. The active pharmaceutical ingredient (API) can be dosed
exactly in little volume.
2. Tableting of the most solid drugs is solvable.
3. The APIs can be produced in large amounts by machines.
4. It is posible the protection of the API against the gastric juice,
resp. enviroment.
5. The dissolution and absorption of the API are regulable.
6. Suitable storage.
7. Good taking possibility.
8. It is possible to make a difference on the base of the shape, size
and colour.
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Grouping of tablets
Oral tabletsUncoated tablets
Coated tablets
Effervescent tablets
Dissolving tablets
Dispensing tablets
Modified release tablets
Tablets in mouthSublinqual tablets
Buccal tablets
Orodispersible tablets (ODT)
Mucoadhesive tablets
Chewable tablets
Other tablets
Tablets in vaginal, urethral, paradentium, etc.
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Tools
A. Dévay: The theory and practice
of pharmaceutical technology,
university textbook, PTE, Pécs, 2013
Upper
punch
die
Lower
punch
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Tools
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EngravingIdeal area, angle and
deep
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Types
Eccentric
Rotation
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Working scheme
Eccentric tablet machine
Hanseaten Exacta 2
1. 2. 3.
4. 5. 6.
Periodic working
Pressure force is efforted by upper punch
Funnel is moving
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Rotation tablet machine
Kilian T400
900 000 tabl/hour
73 punches
Working schemeContinuous working
Pressure force is efferted by both punches
Funnel is fix
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Working mechanism of rotary tablet machine
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RONCHI
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Deformation during loading
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Stages of compression
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Plastic materials: when materials are ductile
they deform by changing shape
(plastic flow).They are two elemetary processes:
1. Mechanical translation:
The parts of the crystals
move in parallel in
response to external
forces, but the connection
between the parts of the
lattice does not cease.
KCl-comprimate, 5kN
Behaviour of materials
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2. Twin formation
The moving of the crystal particles
is not parallel, but one part of the
crystal jumps into a twin position
to another.
KCl-comprimate, 10 kN
Behaviour of materials
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Crimping:the common form of
plastic deformation.
Breaking:response to mechanical
effects, after both plastic
and elastic deformation.
Sulphacetamide sodium compr., 15 kN
Sulphathiazole comprimate, 5 kN
Behaviour of materials
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Sintering:the thermal properties
of the crystal axes are different,
orientation with the axis having
larger heat conductivity (“hot spots”).
Recrystallization:very small crystals can
formed during elastic recovery
after compression maximum.
Theobromine comprimate, 25 kN
Barbitone comprimate, 20kN
Behaviour of materials
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Elastic behaviour:the deformed crystals strive to regain their original form after
pressing. This behaviour causes large internal strain, leading
to breaking inside the tablets (lamination or capping).
Placebo tablet, 10 kN
capping
lamination
Elastic recovery combination
with poor bonding
Behaviour of materials
capping
lamination
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Measurement of compressional force
Compactibility
Instrumentation of tablet machines (strain gauges,
displacement transducer)
-Force-curves (Force-time,
force-displacement diagrams)
Evaluation of force curves
- Energy distribution
- Deformability, plasticity
- Elastic recovery
- Compressional work
- Friction work
- Protocol
Compressibility
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erő
idő
Fmax
A2
A3 A3
100EE
EPl
32
2MS
32
3E
AA
APl
Compressional curves
Plasticity (Emschermann)
Plasticity (Stamm-Mathis)N
time
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Force-time
diagrams
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Excipients
PH102
PH102
Microcrystalline cellulose
Avicel PH102
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Tablettose
Excipients
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up
per
Calculations
Distribution of energy Plasticity
(%)E(%)E
(%)EED
31
2
A
BPl1 100
EE
EPl
32
22
EmschermannStamm-Mathis
dsF
F/lnFFFFW
m
0
s
s alsó
felső
alsófelsőfelső
Friction work
Usefull work
fweffuse WWW
Lubrication coefficientfelső
alsó
F
FR
matricafal
alsófelső
1F
FFU
onmatricafalamaradékerő
erőkilökésiU2
(static)
(kinetic)ejection force
residual force on die wall
A B
up up lo
lo
up
up
lo
uplo
die wall
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Compressibility value
Pr/
( )mass
x x
E m
W
Pa
J kgspec
-1
2
x
H
d h
2
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Compressibility value
Celluloses Pl Pr(mass)
(%) (Pa/Jkg-1)
Avicel PH101 95.08 144.30
Avicel PH301 98.28 93.76
Avicel PH302 97.80 93.99
Vivapur 101 94.64 >> 406.30
Vivapur 102 93.17 378.32
Vitacel M80 82.98 84.21
Vitacel A300 80.09 32.54}microfine
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APIs Pr(mass)
(Pa/Jkg-1)
Phenobarbitone 47.71
Pyridinolcarbamate 129.13
Acetylsalicylic acid (ASA) 76.94
a methyldopa n.m.
Dimenhydrinate n.m.
Compressibility value
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Development of a solid dosage form
Drug
Mixture of excipients
Granulation
pelletization
Tableting
Coating(sugar, film)
Tablet
Filling Capsule
Intestinosolvent
capsule
Granules,
pellets
Coated tablet
Mixture of the drug
and excipients
(API)API
Granules,
pellets
Capsule
Tablet
Coated tablet
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Wet granulation
Dry granulation
Direct compression
Preparing methods
Grinding
Sieving
Blending
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Wet granulationdrugsexcipients
blending
aggregation
dispersion
drying
homogenizing
compression
granulating solution
solvent
Dry granulation
blending
aggregation
dispersion
homogenizing
compression
external phase
drugsexcipients
adjustment of
particle size
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“ The most obvious advantage of direct compression
is economy”
Prof. Shangraw
Blending
Sieving
Weighing
Compression
Direct compression
• reduced processing time
• reduced labor costs
• fewer manufacturing steps
• fewer pieces of equipment
• less process validation
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Requirements
• nontoxic, physiological inert
• free of any unacceptable microbiologic “load”
• physically and chemically stable
• colourless, odourless, tasteless
• obtainable, acceptable cost
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Grouping
Diluents* (amount of API is very small)
Disintegrants* (the tablets should disintegrant to small particles)
Binders*
Adsorbents
Humectants
Hydrophilizing materials
Agents retarding dissolution
Glident*
Lubricants*
Antiadhesive materials*
Antistatics*
Colours, flavours, sweeteners
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Role of disintegrants
- high hydratation into the tablet
- small solubility
- small geling properties
- high binding in tablet
- good flowability
- good compressibility
Requirement
Tablet Granules oraggregates
Originalparticles
disintegration dezaggregation
dis
solu
tion
dissolution
diss
olutio
n
Solution of drug
abso
rpti
on
Drug in blood
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Measurement of swelling force
Mechanism of disintegration• swelling force
• wicking effect
• adsorption heat during wetting
• gas forming
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Grouping
Diluents*
Disintegrants*
Binders*(facilitate the compression, support of good hardness)
Adsorbents
Humectants
Hydrophilizing materials
Agents retarding dissolution
Glident*
Lubricants*
Antiadhesive materials*
Antistatics*
Colours, flavours, sweeteners
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Pressing of Solid Particles
Compressibility and Process
Binding mechanisms
1. Liquid bridges
2. Capillary forces in the
cavities full with liquid
3. Structure-closing linkages
4. Dispersion forces
5. Hardening binders
6. Crystallization of dissolved
material
7. Sinter-bridges, cold binding
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- solid coherent system
- fixed solid particles
- pores among them
Characteristic of texture:
• surface area
• porosity, distribution of pores
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Breaking surface
Szulfacetamid sodium tablet
Binder: Polyvidon
Pressure force: 10 kNSzulfacetamid sodium tablet
Binder: Modocoll
Pressure force: 10 kN
Furosemid tablet
Binder: Klucel MF
Pressure force: 10 kN
Surface
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KCl + Avicel PH 101
10 kN
surface
margin
sideAvicel PH 101
25 kN
Avicel PH 102
2 kN
middle
Mechanical interconnection: form-closing bindings
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Primer poresSecunder pores
1, 2 = primer pores
3= secunder pores
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Grouping
Diluents*
Disintegrants*
Binders*
Adsorbents (e.g. API is fluid, or eutectic is forming)
Humectants (to insure the suitable moisture content)
Hydrophilizing materials (to increase the wettability of the tablet)
Agents retarding dissolution (e.g. buccal or sustained release tablets)
Glident* (to increase the flowability)
Lubricants* (to decrease the friction and sticking)
Antiadhesive materials* (to decrease the adhesion to the punches)
Antistatics* (to decrease the static charge)
Colours, flavours, sweeteners (to correct the unpleasant taste or smell,
or distinction the tablets)
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Influencing factors on the physical parameters
Material factors: quality of substances
shape parameters of particles
particle size
Machine factors: compressional force
compressional speed
type of tablet machine
condition of punches
Preparation condition: composition
technology
storage condition
CTD (Common Technical Documentation)
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Influence of some important factors on the
compression
1. Crystal structure
2. Morphology
3. Flow properties
4. Quality and quantity of binder
5. High pressure force
6. Speed of pressing
7. Mechanism of compression
8. Moisture of material
9. Relative air humidity
10. Condition of punches and dies
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Problems during tableting
1. Abnormal noises in the tableting press
2. Sticking and adhesion to the punches
3. Capping and lamination
• crystal system
• too lot of fine powders
• little amount of binder
• too little moisture
• too high or shock pressing
• worn surface of punches
• air
4. Small mechanical hardness
5. Long disintegration time
6. High mass deviation
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In process control (IPC)
Product (intermedier) Critical parameters
Drug Particle size (distribution)
Powder mixture Homogeneity, moisture content
Granule Particle size, moisture content, content uniformity,
homogeneity, density (loose, tapped), flowing time
Tablet Mass uniformity, strength (breaking , friability), height,
disintegration time, assay, content uniformity,
dissolution, microbiological purity (E. coli,
Staphylococcus aureus, Pseudomonas aeruginosa,
mushroom, pathogen mikroorg.)
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52Fungi threads on the surface of vitamin C tablets
Thank you for your attention!