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< Tablet:Formulation of tablets
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Granulation Processes
(24)
The standard methods frequently used today in tablet manufacturing are granulation and
direct compression. Granulation technique includes wet granulation and dry
granulation/slugging methods wherein binders are added in solution/suspension form
and in dry form respectively. In Direct Compression, binders possessing direct
compressibility characteristics are used. Binder when used in liquid form gives better
binding action as compared to when used in dry form.
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Types of Binders
(18,25-28)
TABLE.5. CLASSIFICATION OF BINDERS
Polyvinyl Alcohols
Polymethacrylates
Partially Pregelatinized
Starch 1500 Colorcon
Maize Starch
Hydroxy Propyl Methyl
Methocel Dow Chemicals
Cellulose
Wolff-Cellulosics
Hydroxy Propyl Methyl
Walocel Natural Starch and
Cellulose
Chemical Company
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Due to ease of manufacture, product stability and high efficiency, the use of Direct
Compression for tableting has increased. For Direct Compression, directly compressible
binders are required which should exhibit adequate powder compressibility and
flowability. Direct Compression binders should be selected on the basis of compression
behavior, volume reduction under applied pressure and flow behavior in order to have
optimum binding performance. The choice and selection of binders is extremely critical
for Direct Compression tablets.
TABLE.8. COMMONLY USED DC BINDERS
Flow Behavior DI TAB > SMCC(50) > DC Lactose , UNI PURE(DW) >
Avicel (PH 101) > UNI PURE(LD)
Compressibility UNI PURE(LD) > SMCC(50) , Avicel (PH 101) > UNI
PURE(DW) , DC Lactose > DI TAB
Crushing Strength UNI PURE(LD) > SMCC(50) > UNI PURE(DW) >
Avicel(PH 101) > DC Lactose > DITAB
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NIR Spectroscopy is applicable for monitoring of wet granulation process when impeller
torque method cannot be applied. Watano et al determined the granulation end point
using agitated fluidized bed where in IR moisture sensor was installed. The properties of
the wet mass obtained from NIR are independent of granulator equipment variables such
as impeller design. Even the powder blending efficiency in the dry mixing phase can be
monitored inline by NIR. NIR spectroscopy could be an excellent tool in wet granulation
measurement.
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Compatibility
The primary criteria is the compatibility of binder with the API & other tablet
components. This is traditionally found by choosing appropriate stability study design.
Currently Differential Scanning Calorimetry (DSC) is used to ascertain compatibility.
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Spreading of Binder
Spreading of binder/granulation solution on the powder blend is of paramount
importance in successful granulation. A binder that spreads easily on particles is superior
as compared to that which shows poor wetting quality. HPMC is a superior binder for
paracetamol as compared to PVP.
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Mixing Time
The mixing time also determines quality of granules. If the wet massing time is higher
(resulting into hard granules), the tablets may fail the dissolution test in certain cases
since drug release from hard granules is altered.
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Type of Granulator
Fluidized Bed Granulator produces porous granules as compared to High Shear
Granulators.
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Process Variables
Higher degree of densification of the granules results due to higher impeller speed as
well as longer wet massing time. And also there is tendency of agglomeration since
liquid saturation increases. Consequently, impeller speed and wet massing time affect
the granule size.
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Apparatus Variables
The apparatus variables in High Shear Mixer have a larger effect on granule growth than
in Fluidized Bed Granulators because the shear forces are dependent on the mixer
construction. The size and shape of the mixing chamber, impeller and chopper vary in
different High Shear Mixers.
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Impeller Movement
Adhesion of wetted mass to the vessel is less if impeller movement is helical. This gives
a narrower granule size and few lumps. In case of High Shear Mixers, adhesion of wetted
mass to the vessel is a problem which can be reduced by proper construction of the
impeller or by coating the vessel with Polytetrafluoroethylene i.e. Teflon.
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Density
Granule density, True Density, Bulk Density may influence compressibility, tablet
porosity, flow property, dissolution and other properties. Higher compression load is
required in case of dense and hard granules which in turn increases the tablet
disintegration and drug dissolution times. Density is usually determined by pycnometer.
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% Compressibility
Compressibility is the ability of powder to decrease in volume under pressure.
Compressibility is a measure that is obtained from density determinations.
% Compressibility = (Tapped density – Bulk density/Tapped density)*100
Compressibility measures gives idea about flow property of the granules as per CARR’S
Index which is as follows :
TABLE.10. CARR’S INDEX
5 – 15 Excellent
12 – 16 Good
18 – 21 Fair
23 – 28 Poor
28 – 35 Poor
35 – 38 Very Poor
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Flow Properties
It is very important parameter to be measured since it affects the mass of uniformity of
the dose. It is usually predicted from Hausner Ratio and Angle Of Repose Measurement.
Hausner Ratio = Tapped Density / Bulk Density
TABLE.11. HAUSNER RATIO
HAUSNER RATIO TYPE OF FLOW
< 25 Excellent
25 – 30 Good
30 – 40 Passable
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Friability
Friability is important since it affects in particle size distribution of granules affecting
compressibility into tablet, tablet weight variation, granule flowability. Friability is
determined carrying out Tumbler Test or using Friability Tester ( Roche Friabilator ) and
% loss is determined.
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Moisture Content
It affects the granule flowability, compressibility as well as the stability of moisture
sensitive drug and therefore should be determined to evaluate the quality of granule.
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Key Phrases