Granulation of pharmaceuticals and excipients

Granulation is a technique for enlarging the particle size by a granulation process. The process is one of the most important operations in the production of solid dosage forms such as tablets and capsules. The target drug and excipients are blended by granulation technology to provide an appropriate particle size distribution, which provides the basis for subsequent dosage form processing. For example, good material homogeneity, flowability and compressibility for the tablet compression process, and excellent stability for transport in the storage process. It also provides the appropriate drug release properties for disintegration and dissolution processes, ensuring the desired dissolution profile and AUC curve in vivo and in vitro, thus ensuring good absorption of the drug and achieving better therapeutic results.

The primary methods of aggregate formation include solid bridging, bonding, sintering, chemical reaction, crystallization, and colloidal particle deposition. At present, according to the methods to promote the adhesion of powder particles, the granulation technology can be divided into two types, dry granulation and wet granulation. Dry granulation and wet granulation are widely used in the pharmaceutical industry, despite the various operational processes involved in the wet granulation process, such as particle growth, drying and sieving. This process is complex, time consuming and expensive, requiring a large amount of space and various devices to overcome the disadvantages of industrialization. However, this product has various advantages over dry granulation products, which leads to the widespread use of wet granulation technology. Wet granulation provides a series of cohesion and cohesion to the powder-forming particles primarily through water, binder solutions or suspensions. Common mechanisms of particle formation include wetting and nucleation, coalescence or growth, consolidation and abrasion/fracture. In the recent studies, researchers have used different modelling methods such as discrete element model (DEM), population balance model (PBM), and computational fluid dynamics (CFD) to simulate the different mechanisms involved in the granulation process. Examples include cellular automata (CA), Monte Carlo method, contact model, hard-sphere model and soft-sphere model. These models can be developed to provide systematic process understanding and process control for dry and wet granulation to ensure the quality of pharmaceutical products. Dry granulation uses mechanical compression (agglomeration) or compaction (rolling) to promote the agglomeration of dry powder particles. Powder mixtures containing pharmaceutically acceptable excipients and starting materials can be compressed into tablets by direct compression or agglomeration or granulation techniques, avoiding both wet and thermal processes. The properties of granulated granules depend on many factors, such as granulation method, types and sizes of drugs and excipients, types, concentrations and volumes of binders and/or solvents, granulation time, drying rate, temperature and time, and so on.