a study on pellets, pelletization techniques and its

www.wjpps.com │ Vol 10, Issue 4, 2021. │ ISO 9001:2015 Certified Journal │

850

Ranjitha et al. World Journal of Pharmacy and Pharmaceutical Sciences

A STUDY ON PELLETS, PELLETIZATION TECHNIQUES AND ITS

EVALUATION PARAMETERS – A REVIEW

Ranjitha K. S.*, Ganesh N. S., Megha J. and Vineeth Chandy

Dept of Pharmaceutics. T. John College of Pharmacy, Bangalore-560083 India.

ABSTRACT

Pelletization is one of the novel techniques for the delivery of the drug

in a modified manner which converts fine powders or granules of bulk

drugs and excipients into small free-flowing, spherical or semi-

spherical particles into pellets (0.5 to 2.0 mm). Pellets are

often modified to provide the desired dose strength and can be

blended to deliver incompatible bioactive agents and different

release profiles. Pellets provide a high degree of flexibility in the

design and development of an oral dosage form, as the oral route for

administration of active medication has become the most versatile,

convenient, and common route. Several methods of Pelletization techniques are available,

among them, Extrusion Spheronization is widely used because of its straightforward steps

involved in pellet production. This article describes the different pelletization methods used

in the pharmaceutical industry for spheroidal particle production and additionally

incorporates the advantages and disadvantages, techniques of pelletization, characterization,

and evaluation of pellets.

KEYWORDS: Pellets, Pelletization techniques, Extrusion spheronization, Evaluation

parameters.

INTRODUCTION

During the 1950s pellets appeared in the field of the pharmaceutical industry. Pellet

formulation processing methods and equipment utilized were quicker, less expensive, and

more efficient.[1]

Pellet are simple small free-flowing spherical particles formed by the

agglomeration of fine powder or granules which can be used to formulate as tablets or

capsules. Oral administration is considered as generally advantageous, easy application and

patient compliance.[2]

The size of the pellets ranges between 0.5 and 2.0 mm. Being small

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 10, Issue 4, 850-863 Review Article ISSN 2278 – 4357

*Corresponding Author

Ranjitha K. S.

Dept of Pharmaceutics. T.

John College of Pharmacy,

Bangalore-560083 India.

Article Received on

10 Feb. 2021,

Revised on 02 March 2021,

Accepted on 22 March 2021

DOI: 10.20959/wjpps20214-18709


851


pellets or multi particulates can distribute evenly in the gastrointestinal tract, resulting in

fewer adverse effects. Pellets also reduce the risk of dose dumping compared to single unit

dosage forms and result in a reproducible bioavailability.[3]

In one single dose of

Multiparticulate Unit System (MUS), pellets are rapidly and homogeneously distributed in

the gastrointestinal tract (GIT). In spite of feeding or fasting conditions, thus reduce the risk

of high local concentration and side effects, increase the contact region between drug and the

GIT, furthermore, enhance drug absorption and lower the fluctuations of peak plasma.[4]

Pellets are prepared by using different technologies such as layering of drug solution,

suspension, extrusion spheronization, and agglomeration, etc. Granulation is generally called

pelletization, agglomeration, or spheronization, and obtained units known as granules pellets,

and spheroids.[1,2]

Ideal properties of pellets

Pellets should possess a smooth surface and spherical shape.

Particle size ranges from 500 to 1500μm.

To preserve the size of pellets the amount of the active ingredient should be

maximum.[5,6]

The flexibility of pellets in the development of dosage form

Fig. 1: The flexibility of pellets in the development of dosage form.[6]

Advantages of pellets

Pellets improve the safety and adequacy of the drug.


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The product’s appearance is improved with fine pharmaceutical elegance.

Flow property of formulation will be enhanced by pellets.

Dose dumping can be avoided by pelletized delivery.

Gastric emptying rate and intestinal transit time can be reduced by pellets.

Pelletization is a convenient method to maintain the suppression of incompatible drugs.

Flexibility in dosage form design and development.

The pellets are utilized to coverup the taste of bitter drugs.

Pellets are non-dusting.

Reduce peak plasma fluctuation.

Pellets reduce the potential side effects without lowering bioavailability.

Pellets having a low surface area to volume ratio provides an ideal shape for the

application of coatings.

Due to their small size and large surface area of absorption pellets are easily dispersed in

the GIT which reduces the peak plasma level fluctuations.[5,6,7,8]

Disadvantages of pellets

The preparation of pellets is an expensive method, which requires trained persons and

specialized equipment.

The size of pellets depends on formulation requirements but usually lies between 1 to 2

mm.[9]

The process of pelletization is a more complicated method.

Pellets are sometimes more rigid which is difficult to compress as a tablet, therefore have

to be encapsulated into a capsule.[5,7]

Excipients used in pelletization

Table 01: Excipients used in pelletization 1.

Spheronisation enhancer MCC, sodium CMC

Release modifier Ethyl cellulose, carnauba wax, shellac

Filler MCC, starch, sucrose, lactose, mannitol

Binder HPC, HPMC,MC, PVP, gelatin , sucrose

Lubricant Calcium stearate, magnesium stearate, talc

Separating agent Kaolin, talc, silicon dioxide

Disintegrant Alginates, croscarmellose, sodium

pH adjuster citrate, phosphate

Surfactant Polysorbate, SLS


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Pelletization techniques

Fig. 02: Pelletization techniques.[6]

1. Agitation

Balling: Inthis technique, to produce finely divided particles, the required amount ofliquid is

added before or during the agitation stage, and this mass undercontinuous rolling or tumbling

motion results in spherical particles. Equipmentused is pans, discs, drums, or mixers.[10]

2. Compaction

a. Compression: Toobtain pellets of definite shape and size the mixture or blends of active

medicamentand excipients are compacted under the pressure. Obtained pellets are of

narrowsize distribution and can be filled into capsules.

b. Extrusion spheronization (Cold mass extrusion – spheronization)

A multi-step process was invented by Nakahara, in 1964. The main advantage of this is to

manufacture drug-loaded spheres with high drug content of up to 90%. This process involves

the dry blending of the active compound along with other ingredients to achieve a

homogeneous powder which may further utilized to make wet mass with the aid of a binder.

Granulation of wetted mass, extrusion of the wetted mass into an extrudate than transferring a

mass to spheronizer to produce spheroids. And drying of the wet pellets in a dryer and at the

end screening to obtain the required particle size was done.[10]


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3. Layering

Layering technique are of two types.

a. Powder layering technique

Initially, lipid core or nuclei is prepared, on it, the successive layer of powdered drug and

excipient or both is deposited. During powder layering, at a pre-determined controlled rate,

the binding solution and finely milled powder are added simultaneously to a bed of starter

seeds In the initial stage the drug particle is subsequently bound with forming pellets with the

aid of a liquid bridge originated from the binding liquid.[9,10]

The successive layering of a

drug and the binder solution continues until the desired pellet size is reached.[11]

b. Solution or suspension layering technique

On starter seeds, the successive layer of solution or suspension of drug substances and

binders is deposited. Starter seeds may be inert material or crystals of granules of the same

drug. Drug particles and other components are dissolved or suspended in the application

medium. The solution or suspension is sprayed on the cores evenly, followed by the drying

phase converts the dissolved material to form a solid bridge between drug substances and

core material by crystallization.[11]

4. Globulation

It is also known as droplet formation, it contains two types namely spray drying and spray

congealing. To generate the spherical particles of pellets, both the process involves the

atomization of hot melts, solutions, or suspensions. The particle size of the pellets produced

is usually small and to maximize the rate of evaporation or congealing the droplet size in the

batch is kept small. To produce dry and highly spherical particles, the drug in solution or

suspension is sprayed with or without excipients into a hot air stream.[13]

When atomized

droplets come in contact with hot air evaporation of the application medium. the drying

continues throughout the process where y the viscosity of the droplets increases till almost the

entire medium is driven off and solid particles are formed. Obtained spray-dried pellets tend

to be porous.[12]

Hot-melt extrusion

It is the process of pumping raw materials with a rotating screw through a die into a product

of uniform shape under controlled conditions, such as temperature, feed rate, and pressure.

Rotating screw imposes mixing and agitation result in the de-aggregation of suspended


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particles in the molten polymer resulting in the mode uniform dispersion. This technique is

simple, efficient, solvent-free that requires fewer processing stages, and does not require

lengthy drying. The main benefit of this technique is the continuous production of spherical-

shaped pellets with narrow range particle size distribution and is used to improve the

bioavailability of drug substances.[13]

Cryopelletization

In this method, liquid droplets are converted into solid spherical particles this technology was

initially developed for lyophilization. In an aqueous-organic solution suspension or emulsion

are dropped into liquid nitrogen to form frozen particles, these particles are then freeze-dried

on lyophilized to remove water or organic solvents.[7]

Freeze pelletization

This technique is a novel and simple technique in which a liquid-solid carrier along with a

dispersed active medicament is introduced as a droplet into an inert and invisible column of

liquid. Narrow size distribution pellets can be produced with this technique. Drying is not

needed as pellets are solid at room temperature. Two types of equipment are used. In the case

of freeze pelletizer І, the molten solid carriers are introduced from the upper portion of the

column, while in the case of freeze pelletizer ІІ the liquid-solid carrier is introduced from the

bottom of the column.[7]

Theory of pellet formation and growth

a. Nucleation

b. Coalescence

c. Layering

d. Abrasion transfer


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Fig. 03: Theory of pellet formation and growth.[9]

Extrusion spheronization

This process was first devised by Reynolds in the year 1970 and also canine Hadley gave his

contribution to the technique. Extrusion spheronization is a commonly used technique for the

production of uniform size pellets with multiple steps.

It is multiple processes of wet mass extrusion which further pursued by spheronisation step to

produce matrix pellets are beads of spheroids.[14,15]

Pellet formation by extrusion spheronization

Fig. 04: Pellet formation by extrusion spheronization.[16]


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Process of extrusion spheronization

Preparation of the wet mass (granulation).

Shaping the wet mass into cylinders (extrusion).

Breaking up the extruded material, rounding the particles into spheres (spheronization).

Drying to achieve the desired amount of final moisture.

Screening to obtain the appropriate pellet size.[17]

Preparation of wet mass

Preparation of plastic mass of the substance with the use of various granulator forms to blend

the powder mixture and the granulation liquid. The planetary mixer, high shear or sigma

blade mixer, etc. are the most common simple granulators used.

Wet mass shaping into the cylinder

The plastic mass prepared undergoes the extrusion process in which pressure is applied to a

mass of particles before the extrudate is formed by flowing out through an orifice. The length

of the extruded material may vary depending on the physical characteristics of the

material.[16,17]

Types of an extruder with schematic representation[18]

Screw extruder

A. Axial screw extruder.

B. Radial screw extruder.

Fig. 05.


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Mechanism

Utilizes a screw to develop the necessary pressure to force the material to flow through

uniform openings.

a) Axial

The screen is placed at the end of the screw, perpendicular to the axis of the screw

b) Radial

The screen is placed around the screw, discharge in the extrudate perpendicular to the axis of

the screw.

A. Sieve extruder

B. Basket extruder

Fig. 06.

A. Sieve extruder

Extrudate falls vertically from the sieve plate.

Mechanism

The rotating or oscillating arm presses the damp material through a sieve.

B. Basket extruder

Extrudate formed in the horizontal plane.

Mechanism

Similar to sieve extruders, except the sieve or screen is part of a vertical cylindrical wall.

Roll extruder[2,18]

Roll extruders operate by feeding material between a roller and a perforated plate ring die.


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A. Internal roller

B. Roller external to die

C. Roller on the flat die plate

Fig. 07.

Mechanism

Roll extruders operate by feeding material between a roller and a perforated plate or ring die

Ram extruder

A piston riding inside a cylinder or channel is used to compress the material and force it

through an orifice on the forward stroke.

Fig. 08: Ram extruder.[17]


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Spheronization

Extruded cylindrically formed particles are uniformly broken into a uniform length in

spheronization and are eventually converted into a spherical shape. The three dimensions of

the agglomerate shape are determined as extrudates are broken into uniform lengths.[13,14]

Schematic representation of spheronizer

Fig. 09: Schematic representation of spheronizer.[2]

Factors influencing the technique of pelletization

1. Rheological properties.

2. Moisture content.

3. Composition of granulating fluid.

4. The solubility of excipients and drugs in granulating fluid.

5. Physical characteristics of starting material.

6. Screen for extrusion.

7. Speed of spheroniser.

8. Drying technique and drying temperature.[11,19]


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Evaluation parameters

1. Particle size distribution

Using an electronic weighing balance, 100mg pellets are weighed. For particle size analysis,

pellets are then moved to a series of sieves with various measurement sizes. Calculate the

percentage retained on each sieve.

2. Surface area

The characteristics of pellets that influence the surface area are mainly the size, shape,

porosity, and roughness of the surface. By calculating the mean diameter, gas adsorption, and

air permeability, it can be determined from particle size distribution.[19,20]

3. Porosity

By scanning the electron microscope, the porosity of pellets can be qualitatively calculated.

By influencing the capillary action of the dissolved drug, the porosity of pellets affects the

rate of release of drugs from pellets.

4. Density

Changes in the formulation of the process will influence the density of pellets.

The degree of compactness of substances is suggested by true density.

a. Tapped density = weight of powder /tapped volume.

b. Bulk density = weight of powder/bulk volume.[19]

5. Hardness and Friability

The friability of pellets is calculated by the Kaul pellet hardness tester using the Erkewa type

tablet friabilator, the hardness of pellets is determined. Pellet determination of hardness and

friability is important because pellets have to withstand handling, shipping, and storage.

6. Tensile strength

Using a tensile apparatus with a 5kg load cell, the tensile strength of pellets is determined.

The load is recorded and the tensile strength is determined by applying the failure load and

the pellet radius.[21,22]

CONCLUSION

Pelletization technology in the pharmaceutical industry has acquired a prominent role in the

current scenario due to its varying degree of character n novel drug delivery systems as well

as in the traditional method. Due to its simple nature, more efficiency, and faster processing,


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the pelletization method has gained more popularity in the pharmaceutical industry. Extrusion

spheronization is a widely used technique in pelletization because of its high efficiency,

greater yield, and is easy to manufacture.

Future prospectives

Pelletization is one of the novel drug delivery techniques that provides an effective way to

deliver the drug in the modified pattern. The Pelletization technique has a very wide range of

applications in the pharmaceutical field. Pelletized activated carbon market by future scenario

trends. It also analyses the industry future trends, risks and entry barriers, status, development

rate, Plastic Pellet Dryers market factors, opportunities and challenges, sales channels,

distributors.

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a study on pellets, pelletization techniques and its

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