Granulation, a technique of particle enlargement by agglomeration, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. During the granulation process, small fine or coarse particles are converted into large agglomerates called granules. Generally, granulation commences after initial dry mixing of the necessary powder ingredients along with the active pharmaceutical ingredient (API), so that a uniform distribution of each ingredient throughout the powder mixture is achieved. Although granules used in the pharmaceutical industry have particle size in the range of 0.2-4.0 mm, they are primarily produced as an intermediary with a size range of 0.2-0.5 mm to be either packed as a dosage form or be mixed with other excipients before tablet compaction or capsule filling.
Granules are produced to enhance the uniformity of the API in the final product, to increase the density of the blend so that it occupies less volume per unit weight for better storage and shipment, to facilitate metering or volumetric dispensing, to reduce dust during granulation process to reduce toxic exposure and process-related hazards, and to improve the appearance of the product. Consequently, the ideal characteristics of granules include spherical shape for improved flow, narrow particle size distribution for content uniformity and volumetric dispensing, sufficient fines to fill void spaces between granules for better compaction and compression characteristics, and adequate moisture and hardness to prevent breaking and dust formation during process.
Granulation is an exemplary of particle design and the properties of the particles acquired after granulation depend on particle size of the drug and excipients, the type, concentration, and volume of binder and/or solvents, granulation time, type of granulator, drying rate (temperature and time), etc. The primary methods by which the agglomerated granules are formed include solid bridges, sintering, chemical reaction, crystallization and deposition of colloidal particles. Besides, binding can also be accomplished through adhesive and cohesive forces by utilizing high viscous binders. The series of mechanisms by which granules are formed from the powder particles encompass wetting and nucleation, coalescence or growth, consolidation, and attrition or breakage.
Blend of powders containing pharmaceutical excipients and API can be compressed into tablets either by direct compression or after making granules by agglomeration or granulation techniques. The granulation technique may be widely categorized in to two types, dry granulation and wet granulation, based on the type of method used to facilitate the agglomeration of powder particles. Dry granulation uses mechanical compression (slugs) or compaction (roller compaction) to facilitate the agglomeration of dry powder particles, while the wet granulation uses granulation liquid (binder/solvent) to facilitate the agglomeration by formation of wet mass by adhesion. Among these two techniques, wet granulation is the most widespread granulation technique used despite the fact that it involves multiple unit processes such as wet massing, drying and screening, which are complex, time consuming, and expensive requiring large space and multiple equipment.
The type of process selection requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, etc. Granulation technologies like roller compaction, spray drying, supercritical fluid, low/high shear mixing, fluid bed granulation, extrusion/ spheronization, etc. have been successful for many decades in the preparation of various pharmaceutical dosage forms. Pharmaceutical granulation technology continues to change, and various improved, modified, and novel techniques and technologies have been made available along the course.
Recent progress in dry granulation
Dry granulation could be achieved either by roller compaction or by slugging. There has not been much progress in the dry granulation technique and technology in comparison to wet granulation, except for one important innovation known as Pneumatic Dry Granulation technology.
Recent progress in wet granulation
Wet granulation is the widely used technique and the granules are produced by wet massing of the excipients and API with granulation liquid with or without binder. Wet granulation has witnessed various technical and technological innovations such as Steam Granulation, Moisture-activated Dry Granulation or Moist Granulation, Thermal Adhesion Granulation, Melt Granulation, Freeze Granulation, Foamed Binder or Foam Granulation, and Reverse Wet Granulation.
