FACTS ABOUT “GRANULATION” AND “PELLETIZATION” IN PHARMACEUTICAL INDUSTRY

In the present day scenario, where novel drug delivery system and controlled drug delivery systems have been developed over the conventional oral solid dosage forms, pellets emerged as a versatile delivery system. Pelletization is a technique to obtain pellets or spherical particles having a dimensions between 0.5 - 1.5 mm. These multiparticulate systems are either compressed into tablets or filled into capsules. It is expected that the pellatizaiton is an effective and efficient approach which can help in improvement of absorption, bioavailability, stability, etc. Pellets can offer therapeutic advantages with affordable cost. Several studies are performed to address the limitations of numerous drugs. R Glycidyl Butyrate (60456-26-0) manufacturer India in this article gives an overview of these with a short description about each development along with its significance and limitations.

What is pharmaceutical processing?

Pharmaceutical Processing is the process of drug manufacturing and can be broken down into a range of unit operations, such as blending, granulation, milling, coating, tablet pressing, filling, and others. The Pharmaceutical manufacturing process has precise requirements and manufacturing guidelines for quality. As a result, pharmaceutical manufacturing equipment must comply with good manufacturing practices.

 Pelletization

 Pelletization can be defined as an agglomeration (size-enlargment) process that converts fine powders or particles of bulk drugs and excipients into small, free-flowing, more or less spherical units, called pellets . Granulation is also known as pelletization, agglomeration or spheronization, and the units obtained are referred to as granules, pellets, agglomerates or spheroids . The general terms “granulation” and “pelletization” are sometimes used synonymously and no clear distinction is made between them. Generally, if a size-enlargement process produces agglomerates of a size distribution within the range of 0.1 to 2.0 mm and a high porosity (about 20-50%), the process may be called “granulation”, and the resulting agglomerates are called “granulates”. “Pelletization” is often referred to as a size-enlargement process that involves the manufacture of agglomerates with a relatively narrow size range, usually with mean size from 0.5 to 2.0 mm, named “pellets”. Pellets have free-flowing properties and a low porosity (about 10 %). The term “spheronization” is more specific, usually associated with spherical units formed by a size-enlargement process that includes a spheronization step where extrudates or agglomerates are rounded as they tumble on a rotating frictional base plate, being named “spheroids”

 

Pelletization Techniques

The term pellet has been used by a number of industries to describe a variety of agglomerates produced from diverse raw materials, using different pieces of manufacturing equipment. In the pharmaceutical industry, pellets can be defined as small, free flowing, spherical particulates manufactured by the agglomeration of fine powders or granules of drug substances and excipients using appropriate processing equipment. The term also has been used to describe small rods with aspect ratios of close to unity.

Various techniques of pelletization

A. Powder layering technique

 B. Solution / suspension layering technique

C. Extrusion- spheronization technique

D. Balling / spherical agglomeration

E. Spray congealing / drying

F. Cryopelletization

G. Melt spheronization

 

 

Reasons For Pelletization

The pharmaceutical industry has developed a great interest in pelletization due to a variety of reasons :

– prevention of segregation of co-agglomerated components, resulting in an improvement of the uniformity of the content;

– prevention of dust formation, resulting in an improvement of the process safety, as fine powders can cause dust explosions and the respiration of fines can cause health problems;

 – increasing bulk density and decreasing bulk volume;

 – the defined shape and weight improves the appearance of the product;

– improvement of the handling properties, due to the free-fl owing properties;

– improvement of the hardness and friability of pellets;

– 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. All these aspects can be considered as technological advantages of pelletization.

Classic properties of pellets

·   Amount of active ingredient needs to be maximum to attain a consistent size of pellet

·   Globular and smooth surface

·   600-1000 µm is the particle size range of pellets

Advantages

Improved flow properties

Improved appearance

Easy dispersion and faster absorption of the drug thereby decreasing fluctuation in plasma peak

Offers flexibility for designing and developing a dosage form

Enhanced safety and efficacy of the drug

Management of incompatible drug separation

Taste masking

Dose dumping is less susceptible

Various drugs shall be coated on pellets to activate different release rates

Disadvantages

Compressing pellets into tablets is problematic as the film coating of pellets is destroyed.

Filling of pellets in a capsule is expensive

Production process is very difficult to control, since several critical process parameters such as

the amount of water needed, time, pressure, etc.

Required highly specialized equipments and qualified personnel

 Granulation

Granulation is the process in which primary powder particles are made to adhere to form larger multiparticle entities called granules. Granulation is required to avoid segregation, enhance the flow of powder, to produce uniform mixture, to produce dust free formulation, to eliminate poor content uniformity and to improve compaction characteristics of mix. Granulation method is mainly divided into two types: wet granulation and dry granulation. Like any other scientific field, pharmaceutical granulation technology also continues to change, and arrival of novel and innovative technologies are inevitable.

 

 

Used Granulation Process

 

A.    Wet granulation that utilize a liquid in the process

B.     . Dry granulation that requires no liquid.

The primary methods by which the agglomerated granules are formed include solid bridges, sintering, chemical reaction, crystallization and deposition of colloidal particles. The dry granulation process is used to form granules without using a liquid solution because the product to be granulated may be sensitive to moisture and heat. Wet granulation involves the massing of a mix of dry primary powder particles using a granulating fluid (the process of adding a liquid solution to powders). The fluid contains a solvent which must be volatile, so that it can be removed by drying, and be nontoxic. Technical and technological progress that helps in development and ease other facilities is always desirable. Obviously, the pharmaceutical granulation techniques and technologies have improved over the years. Nevertheless, efficient and cost-effective manufacturing methods have always been the keen interest of the pharmaceutical industries which helps them in research and development progress globally. During the formulation development, each drug substance poses a unique challenge that must be taken into consideration at the process selection stage by the formulation development scientists. Each technique has its own merits and limitations, and the type of technique and technology selection requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, etc. in addition to the granulation techniques and technologies itself