PHARMACEUTICAL PELLETS

What is pellet?
Small free flowing spherical units ranging in size, prepared by agglomeration of fine powders called pellets.
• Their size and shape allow their administration as injections and also for oral drug delivery.
• Pellets range in size, typically, between 0.5 – 1.5 mm, though other sizes could be prepared.
Why pellets?
• Taste masking: Micropellets are ideal for products where perfect abatement of taste is required. pellets proivide
the masking of unpleasant taste without lowering of bioavailability especially for oral products.
• Immediate release: Administering drugs in pellet form leads to an increased surface area as compared to
traditional compressed tablets and capsules. This would considerably reduce the time required for disintegration and
have the potential for use in rapidly dispersible tablets.
• Sustained release: Pellets are being increasingly used in the manufacture of sustained release dosage form of
drugs. The advantages of the dosage form are well known and some examples are given.
• Extend day time and night time activity of the drugs,
• Reduced dosage frequency of dosage forms,
• Increased patient compliance
Potential lower daily cost to patient due to fewer dosage units, in contrast the whole tabletis released at once in to
the small intestine as the stomach empties itself
• Different types of polymers are utilized for coating of different drugs to enable the sustained release/controlled
release rate of drugs. Chemically incompatible products: At times such ingredients are required to be delivered in a
single dose. In the compressed tablet dosage form separate tablets would have to be administered, but the pellets can
be administered in a single capsule.
• Varying dosage without reformulation
• Pellets have excellent flow properties, due to this, they can be conveniently used for filling capsules and the
manufacturer can vary the dosage by varying the capsule size without reformulating the product
• Pelletization is an agglomeration process that converts fine powders or granules of bulk drugs and excipients into
small, free flowing semi-spherical units.

MECHANISM OF DRUG RELEASE FROM MULTI- PARTICULATES

Diffusion :- On contact with aqueous fluids in the gastrointestinal tract (GIT), water diffuses into the interior of the
particle. Drug dissolution occurs and the drug solutions diffuse across the release coat to the exterior.
Erosion :- Some coatings can be designed to erode gradually with time, thereby releasing the drug contained within
the particle.
Osmosis :- In allowing water to enter under the right circumstances, an osmotic pressure can be built up within the
interior of the particle. The drug is forced out of the particle into the exterior through the coating.
Advantages of Pellets
• Improved aesthetic appearance of the product.
• Coating of drug pellets with different polymers to achieve controlled release rate of drugs.
• For immediate release products large surface area of the pellets enables better distribution, dissolution and
absorption.
• Chemically incompatible products can be formulated into pellets and delivered into single dosage form by
encapsulating them.
• Pellets ensures improved flow properties and flexibility in formulation, development , and manufacture.

RESONS FOR PELLETIZATION

• Prevention of segregation of co-agglomerated
• Improvement of the process safety, as fine powders can cause dust explosions and the respiration of fines can
cause health problems
• The defined shape and weight improves the – appearance of the product
• Controlled release application of pellets due – to the ideal low surface area-to-volume ratio that provides an ideal
shape for the application of film coatings.
• pellets can disperse freely throughout an area of the gastrointestinal tract after administration and consequently
the drug absorbtion is maximized as a large gastrointestinal surface can be involved in this process
 • peak plasma level of the drug can be reduced – by the use of spherical particles with different release rates;
• potential side effects are minimized without markedly lowering drug bioavailability;
• the wide distribution of spherical particles in the gastrointestinal tract limits localized build-up of the drug,
avoiding the irritand effect of some drugs on the gastric mucosa;.

Methods of Pelletization

Extrusion or Spheronization • Extrusion spheronization is widely utilized in formulation of sustained release, controlled
release delivery system. • The main objective of the extrusion spheronization is to produce pellets/spheroids of uniform
size with high drug loading capacity
The extrusion-spheronization process can be broken down into the following steps:
Product features • Dust free • High spherocity • Free flowing • Compact structure • Low hygroscopicity • High bulk
density • Low abrasion • Narrow particle size distribution • Smooth surface

Hot melt extrusion • Hot melt extrusion is a process of converting raw material into a product of uniform shape and
density by forcing it through a die under controlled condition.
• The theoretical approach to understanding the melt extrusion process is therefore, generally presented by dividing the
process of flow into four sections:
• 1) Feeding of the extruder.
• 2) Conveying of mass (mixing and reduction of • particle size).
• 3) Flow through the die.
• 4) Exit from the die and down-stream processing.
Hot melt extrusion Applications in the pharmaceutical industry: In pharmaceutical industry the melt extrusion has been
used for various purposes, such as
1. Improving the dissolution rate and bioavailability of the drug by forming a solid dispersion or solid solution.
2. Controlling or modifying the release of the drug.
3. Masking the bitter taste of an active drug

Fluid-Bed Granulation: Spraying of a granulation solution onto the suspended particles, which then are dried rapidly in
the hot air stream. The process is carried out continuously in a fluid-bed granulator.
Meets all the physical requirements for compression of tablets.
The process of adding a liquid solution to powders involves the massing of a mix of dry primary powder particles using a
granulating fluid. The fluid contains a solvent that must be volatile.
Three Version of fluidized bed granulator.
A. Top-Spray Method
B. Bottom-Spray Method
C. Tangential-Spray Method
Fluid bed granulation process improves the dissolution efficiency of both nimodipine and spironolactone tablets.
Automated, performed in one unit, thus saving costs, transfer losses and time.
Drying of the granulated product to the desired moisture content.
Granulation of the mixture by spraying a suitable liquid binder onto the fluidized (suspended) powder bed.
Pre-blending of the formulation powder, including the active ingredients, fillers, disintegrants, in a flow of air.
The fluid-bed granulation is performed following these steps:
1. Tangential-Spray Method
2. Fluid-Bed Granulation
No need of drying phase since dried granules are obtained by cooling it to room temperature.
Melted binder then acts like a binding liquid. Granulation is achieved by the addition of meltable binder. Binder is in
solid state at room temperature but melts in the temperature range of 50 – 80˚C. e.g. Polyethylene Glycol (PEG) 2000,
4000, 6000, 8000 (40-60 °C)

Melt Granulation
Vitamin A and D can be coated by this process to prevent their deterioration
 A drug solution or suspension is sprayed, with or without excipients, into a hot-air stream, generating dry and highly
spherical particles. Typical Spray-Drying System
Spray-Congealing
Monoglycerides and similar components are spray-congealed. Drugs can be suspended in molten wax and can give
sustain release effect. Also called Spray-Chilling, a technique similar to Spray-Drying but no source of heat is required .

Layering Technique • layering involves the deposition of successive layers of dry powder or liquid droplets of drug with
excipients and binding liquid on to starting inert seed .
Liquid layering: Liquid layering of pellets involves the deposition of successive layers of solutions or suspensions of drug
substances and binders on starter seeds, which may be inert materials and that produce pellets with uniform size
distribution and very good surphace morphology that then dried simultaneously.
• These characteristics are especially desirable in development of controlled release pellets.
• Custom modified conventional coating pans (perforated pans) and various configurations of fluid-bed equipment used
to achieve this.
There are many factors that determine the economic and performance feasability of pellet coating such as drug
solubility used in solution layering, suspension concentration in suspension layering and particle size of suspension.
Micronized drug particles tend to provide pellets that are smooth in appearance. If the particle size of the drug in the
suspension is large, the amount of binder required to immobilize the particles onto the cores will be high, and,
consequently, pellets of low potency are produced. The morphology of the finished pellets also tends to be rough and
may adversely affect the coating process and the coated product.
Powder layering
• It is layering a drug onto starter pellets. When the active ingredient is in powder form, pelletization can be achieved by
spraying starter pellets with the active powder and at the same time a liquid binder solution. The layered pellets are
then dried.
• OR, • Initially, the starter seeds (innert pellets, beads, spheres) are charged into a rotating pan, then wetted by
spraying an adhesive solution. As the wet seeds reach the front end of the pan, the powder added in the vortex adheres
to them.

Cryopeletization
• Cryopeletization is a process where liquid dropletsor powder of a formulation converted into solid spherical pellets by
using liquid nitrogen gas in a fixed medium at -160°C
Application: • It is used as an intermediate holding step
• It is used for long-term storage
• It enables ultra-fast freeze drying
• It is used to halt a fermentation reaction
Advantages of cryopelletization: It is very easy to handle. It produces free-flowing pellet forms. It offers ultra-fast
thawing for consistent and fast reconstitution eliminating the need tofreeze in block form which is difficult to handle.

Dosage form development using pellets

Modified release pellets • Pellets may have one or more layers of different polymer with suitable excipients for
modified release of drug and then formulated as tablet or capsule.
• The use of pellets coated with different polymers and different film thicknesses that allow modulation of the release
rate from pellets over and extended period of time.

Marketed product Example of Tablets & Capsules: Amoxicillin, Pseudoephedrine, Propranolol HCL, Esomeprazole,
Omeprazole, Lansoprazole, Niacin, Duloxetine HCL, Prochlorperazine, Phendimetrazine tartrate etc.

Conclusion • The brief review on pellets &pelletization concludes pelletized dosage forms as one of the most promising
& efficient pathway of novel & multiparticulate Drug delivery System .This pelletization technique has great
advantageover the single unit dosage form.
Now-a-days, pelletization technique is used widely which are unstable drug or have compatibility problem with
excipients. The potential of this technology provide the scope for development of different oral controlled delivery
systems and topical delivery systems.