Pharmaceutical Pellets

Moshiur Rahman ID:1220303646Md Samrul Islam ID: 1321111046MD. Samiul Sady ID:1320705046Md Anik khan ID:1320430046Aminul Islam ID:1230885046

Pharmaceutical PelletsWhat 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 is well known and some examples are given below :

• 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 tabletdosage form separate tablets would have to be administered, but the pellets can be administered ina 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

Extrusion-spheronizationThe extrusion-spheronization process can be broken down into the following steps:

Extrusion Spheronization 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.

Hot melt extrusion

Hot melt extrusion • 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

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 bioavailabilityof 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

GranulationWet Granulation

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.

Meets all the physical requirements for compression of tablets.

Fluid-bed Granulation The process is carried out continuously in a fluid-bed

granulator. Spraying of a granulation solution onto the suspended

particles, which then aredried rapidly in the hot air stream.

Fluid-Bed Granulation

Figure: Three Version of fluidized bed granulator.A. Top-Spray MethodB. Bottom-Spray MethodC. Tangential-Spray Method

Fluid-Bed Granulation The fluid-bed granulation is performed following these steps: ( Tangential-Spray Method ) Pre-blending of the formulation powder, including the active ingredients, fillers, disintegrants, in a flow of

air. Granulation of the mixture by spraying a suitable liquid binder onto the fluidized (suspended) powder

bed. Drying of the granulated product to the desired moisture content.

Parameters Equipment parameters Product parameters Process parameters

Advantages over traditional wet granulation Automated, performed in one unit, thus saving costs,

transfer losses and time. Fluid bed granulation process improves the dissolution efficiency of both nimodipine and spironolactone

tablets.

Fluid-Bed Granulation

Figure: Dissolution Efficiencies of Nimodipine and Spironolactone.

Melt Granulation 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 0C) Melted binder then acts like a binding liquid. No need of drying phase since dried granules

are obtained by cooling it to room temperature.

Spray Drying A drug solution or suspension is sprayed, with or

without excipients, into a hot-air stream, generating dry and highly spherical particles.

Figure: Typical Spray-Drying System. Vitamin A and D can be coated by this process to

prevent their deterioration

Spray Congealing Also called Spray-Chilling, a technique similar to Spray-

Drying but no source of heat is required Drugs can be suspended in molten wax and can give

sustain release effect Monoglycerides and similar components are spray-

congealed

Figure: Spray-Congealing.

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.

Liquid layeringThere 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.

Powder layering

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:AmoxicillinPseudoephedrinePropranolol HCLEsomeprazoleOmeprazoleLansoprazoleNiacinDuloxetine HCLProchlorperazinePhendimetrazine tartrate

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 tech.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 iand topical delivery systems.

Reference • Remington : The Science and Practice of

Pharmacy • http://

www.jpsbr.org/volume_5/JPSBR_Vol_5_Issue_1_htm_files/JPSBR15RS3013.pdf

• http://ijpr.sbmu.ac.ir/article_290_0.html• http://ijpsr.com/bft-article/pelletization-techn

ology-a-quick-review/?view=fulltext