Tablet Binders ( Adhesives, Granulating agent )

Sponsored Links

Tablet Binders

1.5.3 Binders ( Adhesives, Granulating agent)

What will you gain? Why to go for Granulation? Granulation Processes Types of Binders Direct compression (DC) Binders Mechanism of granule formation Near Infrared (NIR) spectroscopy : A tool for granulation end point measurement Factors to be considered in Granulation Evaluation tests for Binders/Granules

Binder is one of an important excipient to be added in tablet formulation. In simpler words, binders or adhesives are the substances that promotes cohesiveness. It is utilized for converting powder into granules through a process known as Granulation. Granulation is the unit operation by which small powdery particles are agglomerated into larger entities called granules. Why to go for Granulation? (24)

Powders/Granules intended for compression into tablets must possess two essential properties : flow property and compressibility.

Flow property/Fluidity is required to produce tablets of a consistent weight and uniform strength. Compressibility is required to form a stable, intact compact mass when pressure is applied. These two objectives are obtained by adding binder to tablet formulation and then proceeding for granulation process. Granules so formed should possess acceptable flow property and compressibility. Some drugs exhibit poor fluidity and compressibility. In such cases binders have to be added for improving flow property and compressibility.

Other reasons for Granulation process are to improve appearance, mixing properties, to avoid dustiness, to densify material, to reduce segregation, in general to either eliminate undesirable properties or to improve the physical and chemical properties of fine powders. 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. Types of Binders (18,25-28)

Table.5. Classification Of Binders


Natural Binders

Synthetic/Semisynthetic Polymer



Methyl Cellulose

Liquid glucose


Ethyl Cellulose


Hydroxy Propyl Methyl Cellulose ( HPMC)

Starch Paste

Hydroxy Propyl Cellulose

Pregelatinized Starch

Sodium Carboxy Methyl Cellulose

Alginic Acid

Polyvinyl Pyrrolidone (PVP)


Polyethylene Glycol (PEG)

Polyvinyl Alcohols


Table.6. Commonly Used Binders




Starch 1500O

Partially Pregelatinized Maize Starch



Hydroxy Propyl Methyl Cellulose

Dow Chemicals


Hydroxy Propyl Methyl Cellulose


Natural Starch and Chemical Company



BASF Company



BASF Company



BASF Company

Table.7. Characteristics Of Commonly Used Binder




Starch Paste


- Freshly prepared starch paste is used as a binder.

- Its method of preparation is very crucial.

Pregelatinized Starch (PGS)

[Partially and Fully PGS]


(Direct Compression)


(Wet Granulation )

- It is starch that have been processed chemically and/or mechanically to rupture all or part of the granules in the presence of water and subsequently dried.

- It contains 5% free amylose, 15% free amylopectin and 80% unmodified starch.

- Obtained from maize, potato or rice starch.

- It is multifunctional excipient used as a tablet binder, diluent, disintegrant and flow aid.

- They enhance both flow and compressibility and can be used as binders in Direct Compression as well as Wet Granulation.

- High purity PGS allow simplified processing as they swell in cold water and therefore reduce time/costs compared with traditional starch paste preparation.

Hydroxypropyl Methyl Cellulose (HPMC)


- Comparable to Methyl Cellulose.

- Used as a binder in either wet or dry granulation processes.

Polyvinyl Pyrrolidone (PVP)


- Soluble in both water and alcohol.

- Used in wet granulation process.

- It is also added to powder blends in the dry form and granulated in situ by the addition of water, alcohol or hydroalcoholic solution.

- Valuable binder for chewable tablets.

- The drug release is not altered on storage.

Polyethylene Glycol (PEG) 6000


- Used as a meltable binder.

- Anhydrous granulating agent where water or alcohol cannot be used .

- It may prolong disintegration time when concentration is 5% or higher

- It improves the plasticity of other binders. Direct compression (DC) Binders (29)

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

Dc Binder



AvicelO (PH 101)


FMC Corporation

SMCCO (50)


Penwest Pharmaceutical


Partially PGSc

National Starch

& Chemical


Low density starch

National Starch & Chemica

DC LactoseO

DC lactose anhydrous

Quest International Group




a - Microcrystalline Cellulose, b - Silicified Microcrystalline Cellulose, c - Pregelatinized Starch, d - Dibasic Calcium Phosphate Dihydrate

Table.9. Characteristics Of Dc Binders

Flow Behavior

DI TABO> SMCCO(50) > DC LactoseO , UNI PUREO(DW) > AvicelO (PH 101) > UNI PUREO(LD)


UNI PUREO(LD) > SMCCO(50) , AvicelO(PH 101) > UNI PUREO(DW) , DC LactoseO > DI TABO

Crushing Strength

UNI PUREO(LD) > SMCCO(50) > UNI PUREO(DW) > AvicelO(PH 101) > DC LactoseO> DI TABO Mechanism of granule formation (30)

Granules are formed in three stages:

Nucleation: Here, the particles adhere due to liquid bridges which are the initiation step of Granulation. These adhered particles play a role of nucleus for further enlargement of granules.

Transition: Enlargement of nucleus takes place by two possible mechanisms. Individual particle adhere to the nucleus or two or more nuclei combine among themselves.

Ball growth or enlargement of the granule: Ball growth occurs either by Coalescence or Breakage or Abrasion Transfer or Layering. In Coalescence a larger granule is formed when two or more granules are united. In Breakage granules break and the fragments of granule adhere to other granules. This forms a layer of material over intact granules. In Abrasion Transfer granule material are abraded through attrition by the agitation of granule bed and abraded material adheres to other granules resulting into enlarged granules. In layering particles adheres to the already formed granules increasing their size. Near Infrared (NIR) spectroscopy : A tool for granulation end point measurement (31)

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. Factors to be considered in Granulation (24,30,32)


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.

Characteristics of drugs and other excipients

The drugs characteristics like its compressibility, particle size, surface area, porosity, hydrophobicity, solubility in binder are important while fixing a granulation process. The drug that exhibits poor compressibility requires the use of a strong binder (liquid glucose, sucrose, etc.) while the drugs that exhibit good compressibility can be successfully handled using a weak binder ( starch paste etc.,). Fine and porous particles requires higher amount of liquid binder as compared to coarse particles. Hydrophilic drug/excipients exhibiting absorption characteristics require higher volume of binder as compared to hydrophobic drug/excipients. The granule quality (size , friability) is governed by the solubility of the drug in the granulation solution.

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.

Type and quantity of Binder

The uniformity of the particle size, hardness, disintegration and compressibility of the granulation depends on type and quantity of binder added to formulation. As for example hard granulations results due to stronger binder or a highly concentrated binder solution which require excessive compression force during tableting. On the other hand, fragile granulations results due to insufficient quantity of binder which segregates easily. Larger quantities of granulating liquid produce a narrower particle size range and coarser and hard granules i.e. The proportion of fine granulates particle decreases. Therefore the optimum quantity of liquid needed to get a given particle size should be known in order to keep a batch to batch variations to a minimum.

Temperature and Viscosity

The temperature and viscosity of binder is also important. Fluid (less viscous) binder exhibit good spreading behavior.

Method of Addition of Binder

The method of addition of binder is also important. PVP can be used as solution as a binder or it may be dry blended with powders and later activated by adding water. Distribution of binder is favored if it is dispersed instead of pouring it.

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.

Material of Construction of Granulator

The material of construction of granulator determines the volume of binder required as well as granule size distribution. Any vessel wall which are wetted easily by binder demands the need of higher volume of binder. As for example vessel wall made up of Stainless Steel require higher volume of binder as compared to vessel made up of plastics (PMMA - Polymethylmethacrylate and PTFE - Polytetrafluoroethylene i.e. Teflon). In case of PMMA and PTFE due to high contact angle, all granulating liquid is forced immediately into the powder bed and gives narrow particle size distribution. While in case of steel, due to less contact angle liquid layer formed on the wall surface which in turn causes inhomogeneous distribution of liquid over the powder bed resulting into broader granule size.

Type of Granulator

Fluidized Bed Granulator produces porous granules as compared to High Shear Granulators.

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.

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.

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. Evaluation tests for Binders/Granules (1)

Compactness, physical and chemical stability, rapid production capability, efficacy are some of the characteristics that make tablet a ruling dosage form. These characteristics depend on the quality of granules from which it is made. The characteristics of granules produced are affected by formulation and process variables. So it becomes essential to evaluate the granule characteristics to monitor its suitability for tableting.

Particle Size and Particle Size Distribution

The particle size of granules affect the average tablet weight, tablet weight variation, disintegration time, granule friability, granulation flowability and the drying rate kinetics of wet granulations. Therefore the effects of granule size and size distribution on the quality of tablet should be determined by formulator. The methods usually adopted for measurement of particle size and particle size distribution includes Microscopy, Sieving, Conductivity test.

Surface Area

Surface area of the drug effects upon dissolution rate especially in cases where drug have limited water solubility. The two most common methods for surface area determination are Gas Adsorption and Air Permeability.


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.

% 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

% Compressibility

Flow Description

5 - 15


12 - 16


18 - 21


23 - 28


28 - 35


35 - 38

Very Poor

> 40

Extremely Poor

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



Less than 1.25

Good Flow

1.25 - 1.5


More than 1.5

Poor Flow

Angle of Repose (F) is the maximum angle between the surface of a pile of powder and horizontal plane. It is usually determined by Fixed Funnel Method and is the measure of the flowability of powder/granules.

F = tan-1 (h / r) where, h = height of heap of pile

r = radius of base of pile

Table.12.Angle Of Repose (F)



< 25


25 - 30


30 - 40


> 40

Very Poor


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.

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.

Key Phrases

OBinders are added in tablet formulation to have required flow property and compressibility of powders.

OWet Granulation, Dry Granulation/Slugging, Direct Compression are major granule manufacturing methods.

ODirect Compression Binders are more efficient than conventional binders.

OPregelatinized Starch is used as multifunctional excipient: tablet binder (wet granulating agent as well as direct compression binder), diluent, disintegrant and flow aid.

OPolyethylene Glycol used as meltable binder.

OGranules are formed in three stages: Nucleation, Transition and Ball Growth.

ONIR a tool for granulation end point measurement and is better than torque impeller method.

OCompatibility of binder with API and other excipients, characteristics of binder, process variables, and apparatus variables affects the quality of granules.

OGranules have to be evaluated in order to measure its suitability for tableting.

About the Author

Dr.Mukesh Gohel's picture
Author: Dr.Mukesh Gohel

Dr. Mukesh Gohel is principal, professor at the LMCP, Ahmedabad served in academics for more than 40 years. He provides training in leading pharmaceutical industries in the areas of Design of Experiments and Quality by Design. His current areas of interest are direct compression and improvement of drug dissolution.

You May Also Like..