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Tablet Binders

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19 April 2016 No comments

Tablet binders are one of the most essential elements when it comes to the tablet's formulation. The binders, also called as adhesives are the ingredients that aid the other ingredients to mix together as they promote cohesiveness. Through granulation, the powder is turned into granules. Granulation is a process where powder substances are accumulated to form larger particles called as granules.

Why Granulation

When powdery particles or granules are intended for compression into a tablet, they must have these important properties:

  • Flow property - consistent weight and uniform strength of the tablet
  • Compressibility - ability of the tablet to remain intact, compact and stable even when pressure is applied

These properties are achieved when binders are added to the formulation after which, the materials will undergo the granulation process. The granules that are formed from the process must exhibit excellent flow property and compressibility. Some tablets may show poor fluidity and compressibility. In this instance, binders are added to improve its flow and compressibility.

Aside from the ones mentioned above, granulation would also help the tablet achieve the desired appearance, avoid dustiness, mixing properties, decrease segregation and eliminate undesirable properties and improve the physical and chemical properties of the powder.

Granulation Process

The two most common method used in the industry today involves direct compression and granulation. Direct compression involves using the binders that have
direct compressibility. The liquid form of the binder is more effective than the ones in dry form. Granulation on the other hand involves the use of wet
and dry granulation and binders in solution or suspension form are added.

1.5.3.3 Types of Binders
(18,25-28)

Table.5. Classification Of Binders

SugarsNatural BindersSynthetic/Semisynthetic Polymer
SucroseAcaciaMethyl Cellulose
Liquid glucoseTragacanthEthyl Cellulose
GelatinHydroxy Propyl Methyl Cellulose ( HPMC)
Starch PasteHydroxy Propyl Cellulose
Pregelatinized StarchSodium Carboxy Methyl Cellulose
Alginic AcidPolyvinyl Pyrrolidone (PVP)
CellulosePolyethylene Glycol (PEG)
Polyvinyl Alcohols
Polymethacrylates

Table.6. Commonly Used Binders

BINDERCATEGORYMANUFACTURER
Starch 1500OPartially Pregelatinized Maize StarchColorcon
MethocelOHydroxy Propyl Methyl CelluloseDow Chemicals
WalocelOHMHydroxy Propyl Methyl Cellulose

Wolff-Cellulosics

Natural Starch and Chemical Company

LuvitecOPolyvinylpyrrolidoneBASF Company
LuvicrossOPolyvinylpyrrolidoneBASF Company
LuvicaprolactamOPolyvinylcaprolactamBASF Company

Table.7. Characteristics Of Commonly Used Binder

BINDERSPECIFIED CONCENTRATIONCOMMENTS
Starch Paste5-25%w/w

- Freshly prepared starch paste is used as a binder.

- Its method of preparation is very crucial.

Pregelatinized Starch (PGS)

[Partially and Fully PGS]

5-10%w/w

(Direct Compression)

5-75%w/w

(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)2-5%w/w

- Comparable to Methyl Cellulose.

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

Polyvinyl Pyrrolidone (PVP)0.5-5%w/w

- 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) 600010-15%w/w

- 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 Binders

The use of Direct Compression for tablets is increasing due to the ease of manufacturing, the high efficiency and stability of the product. Direct compression involves using directly compressible binders that have high flowability and compressibility. In order to obtain optimum binding performance, manufacturers must use direct compression binders that have excellent volume reduction when under applied pressure and should also base selection on the compression and flow behavior. It is especially important for Direct Compression tablets.

Table.8. Commonly Used Dc Binders

Dc BinderClassManufacturer
AvicelO (PH 101)MCCaFMC Corporation
SMCCO (50)SMCCbPenwest Pharmaceutical
UNI-PUREO(DW)Partially PGSc

National Starch

& Chemical

UNI-PUREO (LD)Low density starchNational Starch & Chemica
DC LactoseODC lactose anhydrousQuest International Group
DI TABODC-DCPDdRhodi

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

Table.9. Characteristics Of Dc Binders

Flow BehaviorDI TABO> SMCCO(50) > DC LactoseO , UNI PUREO(DW) > AvicelO (PH 101) >
UNI PUREO(LD)
CompressibilityUNI PUREO(LD) > SMCCO(50) , AvicelO(PH 101) > UNI PUREO(DW) , DC LactoseO >
DI TABO
Crushing StrengthUNI PUREO(LD) > SMCCO(50) > UNI PUREO(DW) > AvicelO(PH 101) > DC Lactose O> DI TABO

Granule Formulation Stages:

  • Nucleation in this stage, the particles stick to one another due to the liquid bridges. The particles that form serves as the nucleus of the granule.
  • Transition this stage involves the enlargement of the nucleus either by other particles sticking to the nucleus or several nuclei combining with one
    another.
  • Enlargement the granules would form a ball shape and grow in size due to

(a.) coalescence two or more granules unite into one

(b) breakage some granules break and adhere to other granules

(c) abrasion abraded materials and other granules in the granule bed stick to the formed granule through agitation of the bed.

(d) layering particles stick to the formed granule

Near Infrared Spectroscopy (NIR) Measuring Granulation End Point

NIR is used to monitor the wet granulation process when the impeller torque is not used. Watano et al determined the end point for granulation by using
agitated fluidized bed. The IR sensor is installed and the wet mass properties are obtained independent of the impeller method. The NIR can also be used to
monitor powder blending efficiency during the dry mixing phrase but is more ideal for measuring in the wet granulation process.

Factors to be considered:

  • Compatibility. Compatibility of the binder with other components. The Differential Scanning Calorimetry helps in determining compatibility.
  • Drug characteristics. The characteristics of the drugs used is important during the granulation process. Characteristics such as size, porosity, compressibility, solubility and hydrophobicity can affect the process. Drugs that have poor compressibility would require strong binders whereas porous ones would need a high level of liquid binder. Drugs that have high absorption rate would require higher volume of binder.
  • Spreading of Binder. To make the process successful, spreading the binder together with the powder blend is important. An excellent binder is one that can be easily spread out; an example would be HPMC.
  • Binder quality and type. The uniformity of the tablet's features depends on the quality of the binder added in the formulation. High concentration of binder can cause hard granulation while insufficient quantity of the binder would result to fragile granulation. Large quantities of granulating liquid can result to coarse and hard granules. In order to ensure that variations are limited and uniformity is reached, the quantity of the liquid added should already be prepared and measured beforehand.
  • Temperature and Viscosity. Less viscous binders would result to excellent spreading.
  • Adding Binders. The way binders are added is also important. PVP, can be used as a dry or liquid solution and added to the formulation. It is best to disperse the binders than pouring directly to the mix.
  • Mixing time. The quality of the granules may also be affected by the mixing time. If the wet mass time is higher, it would result to hard granules and the tablet failing the dissolution test as the drug release time is altered.
  • Granulator Construction Materials. The type of construction material affects the volume of the binder and the granule size being distributed. Vessel walls that are wetted easily by binders would require a high volume of binders, example of which are stainless steel vessels that would require higher binder volume than vessels that are made of plastics such as PMMA or Teflon. The use of PMMA or PTFE would narrow the particle size distribution due to its high contact angle whereby all liquids are forced directly to the powder bed. With stainless steel, this is different as less contact angle liquid layer is formed in the wall surface causing inhomogeneous distribution of the liquid over the powder bed resulting to broader granules.
  • Granulator type. Fluidized bed granulator produces porous granules unlike those produced by the High Shear granulator.
  • Variable Process. Higher impeller speed and longer wet massing time can affect the size of the granules. Agglomeration is also a possibility due to the increase in liquid saturation time.
  • Variables Apparatus. The apparatus used can also affect the growth of the granules. Using the High Shear Mixer will result in larger granules than using Fluidized Bed Granulators; this is due to the construction of the mixer. The shape, size chopper and impeller of the mixing chamber is different in each of the apparatus.
  • Impeller movement. Wet mass sticks to the vessel less if the impeller movement is helical resulting in few lumps and narrow granule size. This is usually the problem when using the High Shear Mixers as wet mass sticks to the vessel; to reduce this problem, coating of the vessel with polytetrafluoroethylene or correct construction of the impeller must be observed.

Binders Evaluation Test

Below are some of the characteristics that affect the quality of the granules. These characteristics are affected by the variable process as well as the formulation which have to be constantly evaluated and monitored to determine the suitability for the tableting.

  • Physical and chemical stability
  • Efficacy
  • Compactness
  • Fast production capability

Particle Size and Distribution

The granule size affects the disintegration time, average tablet weight, variation, granule friability, drying rate kinetics of wet granulation and granulation flowability. The formulator determines the quality of the tablet which in turn affects the granule size and distribution. The measurement commonly used to measure the size and distribution includes Conductivity Test, Microscopy and Sieving.

Tablet Surface Area

In certain instances where the drugs have limited water solubility, the surface area of the drugs is measured especially during dissolution. Common methods used include Air Permeability and Gas Adsorption.

Density

Where granules are dense and hard, higher compression load is needed to help increase the drug dissolution time and tablet disintegration. Pycnometer is usually used to determine density. The bulk density, granule and true density can influence the porosity, flow property, dissolution and compressibility of the tablet.

Percentage of Compressibility

Compressibility is defined as the ability of the powder to decrease its volume when subjected to pressure. It is measured by obtaining the density determination as follows:

% Compressibility = (Tapped density - Bulk density/Tapped density)*100

The compressibility measurement gives an idea on the flow property of the granules as per CARR'S Index:

Table.10. Carr's Index

% CompressibilityFlow Description
5 - 15Excellent
12 - 16Good
18 - 21Fair
23 - 28Poor
28 - 35Poor
35 - 38Very Poor
> 40Extremely Poor

Flow Properties:

Measuring the Flow Properties is important as it affects the mass of uniformity of the dose. The Flow is measured by using the Hausner Ratio or the Angle of Repose Measurement.

Hausner Ratio = Tapped Density / Bulk Density

Table.11. Hausner Ratio

HAUSNER RATIOTYPE OF FLOW
Less than 1.25Good Flow
1.25 - 1.5Moderate
More than 1.5Poor Flow

The Angle of Repose (F) is defined as the max angle between the horizontal plane and the powder surface. It is measured by the Fixed Funnel Method.

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

r = radius of base of pile

Table.12.Angle Of Repose (F)

ANGLE OF REPOSETYPE OF FLOW
< 25Excellent
25 - 30Good
30 - 40Passable
> 40Very Poor

Friability

The Friability is important as it affects the size distribution of the granules which in turn affects the compressibility, weight variation and granule
flowability. It is measured via the Tumbler Test or the Friability Test/Roche Friabilator and the % loss is determined.

Moisture Content

The moisture content affects the compressibility, flowability and the stability of moisture sensitive drugs and as such should be determined in order to check the granulator's quality.