Role of Granulation Process in Pharmaceutical Industry

Granulation process  is a ‘‘ process whereby small particles are gathered into larger, permanent masses in which the original particles can still be identified.’’ Pharmaceutical granulation is the rapid breakdown of agglomerates is important to maximize the available surface area and aid in solution of the active drug. In ancient times the granulation process used within the pharmaceutical industry but in modern time, granulation technology has been widely used by a wide range of industries, such as Pharmaceutical. ‘‘granulated’’ material is derived from the Latin word ‘‘granulatum,’’ meaning grained. The fundamental research on mixing, segregation mechanisms of powder, surface chemistry, and material science are necessary to develop the theoretical framework of granulation technology. The granulated material can be obtained by direct size enlargement of primary particles, or size reduction from dry compacted material. These industries employ agglomeration techniques to reduce dust, provide ease of handling, and enhance the material’s ultimate utility. Granulation is process of particle designing.

Granulation methods:  Two types

1.  Wet methods which utilize some form of liquid to bind the primary particles.

2. Dry methods which do Granulation Minimizes the technical risks.

1. Wet granulation technology: It is employed low-shear mixers or the mixers/blenders normally used for dry blending such as ribbon mixers. There are a number of products currently manufactured using these low-shear granulators. The process control and efficiency has increased over the years; however, the industry has embraced high-shear granulators for wet granulation because of its efficient and reproducible process and modern process control capabilities.

2. Dry methods: Dry compaction technique like roller compaction is commonly used  in the Pharmaceutical  industry. There are a number of drug substances which are moisture sensitive and cannot be directly compressed.

Application of Granulation technology in Pharmaceutical Industry: Pharmaceutical granulation process is used for tablet and sometimes capsule dosage forms; however, in some applications the process is used to produce spherical granules for the modified release indications or to prepare granules as sprinkles to be used by pediatric patients.

Granulation of Pharmaceutical Compounds: Pharmaceutical compounds are granulated due to

1. To increase the uniformity of drug distribution in the product

2. To densify the material

3. To enhance the flow rates and rate uniformity

4. To facilitate metering or volumetric dispensing

5. To reduce dust

6. To improve the appearance of the product.

7.  Granulation encountered the incomplete description behavior of powders in general.

Various Drying Techniques for Granulation

Sr. No.	Granulation Techniques	Drying techniques
1	Wet granulation	Tray or fluid-bed dryer
		Tray or fluid-bed dryer
		Vacuum/gas stripping/microwave
		Spray dryer
		Extrusion/ Spheronization /Pelletization
2	Dry granulation Process	Direct compression
		Slugging Mill
		Roller compactor Compacts milled

.

Granulation Mechanisms:  These include wetting and nucleation, coalescence or growth, consolidation, and attrition or breakage. Initial wetting of the feed powder and existing granules by the binding fluid is strongly influenced by spray rate or fluid distribution as well as feed formulation properties, in comparison with mechanical mixing.

Role of Binders in wet-granulation process: Binders are adhesives that are added to solid dosage formulations. The primary role of binders is to provide the cohesiveness essential for the bonding of the solid particles under compaction to form a tablet. In a wet-granulation process, binders promote size enlargement to produce granules and thus improve flowability of the blend during the manufacturing process. Binders may also improve the hardness of the tablets by enhancing intragranular as well as intergranular forces. In a direct compression process, binders often act as fillers and impart compressibility to the powder blend. The cohesive properties of binders may reduce friability of the tablets and thus aid in their durability and elegance.

Examples:

 Natural Polymers:  Starch, Pregelatinized Starch

Synthetic polymers:  PVP, Methyl cellulose, HPMC

 New Natural and Synthetic binders:  Khaya gum, Leucaena leucocephala seed gum,   Anacardium occidentale gum, Gellan gum, Combination of detarium gum and veegum.

 New synthetic binders:  Maltrodextrins, Chitosan derivatives

Granulation techniques: The choice of granulation technique depends on various factors such as chemical and physical stability of the final dosage form, intended biopharmaceutical performance.

v  High- and low-shear granulation

v  Roller compaction

v  Spray drying

v  Fluid-bed granulation

v  Extrusion speronization

v  Melt granulation  and Pelletization

v  Effervescent Granulation

Granulation Characterization: Granulation is a process used to prevent segregation of formulation components in a powder blend, bulk volume of granulation, improve blend flow, content uniformity, compressibility, and other properties. Chemical properties are equally important due to their impact on specifications of a dosage form such as content uniformity, chemical purity, and in vitro performance. In vivo performance such as bioequivalence done because it determines whether a pivotal   bioequivalency batch passes or fails. Granule Size affect the dissolution performance which ultimately affect bioequivalence study. Physical characterization can be performed at molecular, particulate, or bulk (macroscopic) levels.  

Different Parameters and Methods for Characterization of Granules

Sr. No.	Parameters	Method
1	Particle Morphology	Optical microscopy
2	Particle Size Distribution	Sieve analysis, laser light scattering
3	Nature	Powder X-Ray Diffraction
4	Thermal Analysis	DSC, TGA, DTA
5	Identification	Near-infrared (NIR) spectroscopy
6	Surface Area	Gas adsorption
7	Granule Porosity	Mercury intrusion methods
8	Granule Strength	Development of a Formulation
9	Granule Flowability and Density	Mechanical Method, Hopper Method, Density Appratus