Dr. Mekaiel Amiel Mekaiel M.Sc. Pharmaceutical Technology

Technology of Solid Dosage Forms

&Disperse Systems

Pellet Production Technologies

Pellet Production Technologies

Learning Objectives

By the end of this session student should be able to:

1. To explain the detailed formulation and manufacturing unit

operation involved in the manufacture of pellets.

2. Identify the excipients used and their role/function in the

formula.

3. Describe different techniques employed in production of

pellets.

Content

1. Introduction

2. Pelletization vs. granulation.

3. Advantages and disatvantages

4. Pelletization techniques

Introduction:

Difinition:

Pelletization can be defined as an agglomeration process

that converts fine powders or particles of bulk drugs and

excipients into small, free flowing, more or less spherical

units, called pellets.

• This technique enables the formation of spherical beads or

pellets with a mean diameter usually ranging from 0.5 to 2.0

mm.

• It can be coated and usually used in controlled release

dosage forms.

Pelletization vs. granulation.

• The general terms “granulation” and “Pelletization”

are sometimes used synonymously and no clear

distinction is made between them.

• Generally if agglomerates size distribution within the

range of 0.1 to 2.0 mm and a high porosity (about 20-

50%), this process may be called granulation.

Technological Advantages

1. Improvement of the uniformity of the content

2. Prevention of dust formation.

3. Increasing bulk density and decreasing bulk volume.

4. The defined shape and weight improves the appearance of the product.

5. Improvement of the handling properties, due to the free-flowing properties .

6. Improvement of the hardness and friability of pellets.

7. 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.

Therapeutic Advantages

1. Pellets can disperse freely throughout an area of the gastrointestinal tract

2. Pellets reduce peak plasma fluctuations and minimize potential side effects

3. Avoiding the irritant effect of some drugs on the gastric mucosa

4. Modified-release multiparticulate delivery systems are less susceptible to dose dumping than single-unit dosage forms

1. Often pellets can not be pressed into tablets because they are too rigid. In that case, pellets have to be encapsulated into capsules.

2. The production of pellets is often an expensive process and / or requires highly specialized equipment.

3. The control of the production process is difficult (e.g. the amount of water to be added is critical for the quality of the pellets and overwetting can occur very easily).

Disadvantages

Pelletization techniques

1. Extrusion/ Spheronisation.

2. Fluid-bed granulation.

3. Spray-drying.

4. Dry powder layering.

5. Solution and suspension layering.

6. Spray-congealing.

Extrusion-Spheronization:-

• Extrusion is necessary first step in the extrusion-spheronization process.

• The size of the sphere are determined by the diameter of the extrudate used.

The extrusion-spheronization process can be broken down into following steps:-

Extrusion process

1. Screw Extruders

2. Screen or Basket Extruder

3. Gear Extruder

Screw extruder:-

• Commonly used in industrial application.

• Higher pressure and heat can degrade

pharmaceutical products.

Screw extruder

Screen or basket extruder:

Basket Extruder

- Lower density extrudate.

- Relatively high throughput.

Gear extruder:

• Produces relatively high density.

• Gears are robust and last longer

Gear Extruder

Spheronization

• Spheronization is a process of forming a spherical particles

from different rod shapes , by extrusion , that has a diameter

ranging from 0.5 to 1 mm .

Cont.

• The size of the spheres are determined by the diameter of the

extrudate used for the spheronization process. For example, in

order to obtain spheres with a diameter of 1 mm, a 1 mm screen is

used on the extruder.

Spheronization machine design

• In principle the basic machine consists of a rotating friction disk,

designed to increase friction with the product, which spins at high

speed at the bottom of a cylindrical bowl.

Table summarizing the different types of spheronizers for

pharmaceutical production and development :

Equipment Description Main use

Micro spheronizer A Bench Top Laboratory

Unit

Laboratory:small quantity

Spheronizer-120 Bench top Laboratory/experimental

Spheronizer-250 Lab scale bench top Low cost high output

Spheronizer-380 A Production or Pilot Plan

Spheronizer

Quality spheroids output

Spheronizer-500 A Production or Pilot Plan

Spheronizer

Quality spheroids output

Main stages in the fluid bed

Drying:

Granulation / agglomeration

Powder coating / particle coating:

Pelletizing

Types of fluid bed technologies

Top spray Bottom spray Tangential spray

Tangential Spray(Rotor Process)

Process Parameters:

•Liquid addition rate

•Inlet air temp.

•Humidity

•Atomization air pressure

•Binder type and concentration

•Disk speed

•Disk gap

Spray-drying

─Spray-drying represents another process based

on globulation.

─During spray-drying, a drug is solution or

suspension is sprayed, with or without excipients,

into a hot-air stream, generating dry and highly

spherical particles.

Operating conditions:

1. Inlet air temperature: 180- 250 Co .

2. Inlet moisture content 75-85%.

3. Spray rate: 2290kg\hr

4. Outlet air temperature: 80-115Co

5. Air flow rate: 31500kg\hr.

6. outlet moisture content: 3-3.5%.

Advantages: 1. The spray-dried powder particles are homogenous, approximately spherical,

nearly uniform in size.

2. This technique is suitable for development of controlled-released pellets.

3. It is generally employed to improve dissolution rates and bioavailability of

poor soluble drugs.

4. This method is applied for heat sensitive pharmaceuticals: amino acids,

antibiotics, ascorbic acid, liver extracts, pepsin and similar enzymes, protein

hydrosylate and thiamine.

5. Particle size and size distribution, bulk density, porosity, moisture content,

flowability and friability can be easily controlled by the design and operation

of the spray drier.

Spray-congealing:

Spray-congealing is similar to spray-

drying, it is also called spray-

chilling.

In spray-congealing the drug is allowed to

melt, disperse or dissolve in hot melts of

gums, waxes, fatty acids, or other melting

solids.

The dispersion is them sprayed into a

stream of air and other gases with a

temperature below the melting point of the

formulation components, under appropriate

processing conditions, spherical congealed

pellets are obtained.

Thank You