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Compaction, Compression and Consolidation in Pharmaceutical Industries

Compressibility and compactability are the defining features of medicinal powder's compaction characteristics. The capacity to create mechanically robust compacts is known as compactability, whereas compressibility refers to the powder's deformability under pressure. Compaction, in the context of pharmaceutical powders, involves the combined processes of compression and consolidation between the solid particles and gaseous phase, caused by an external force. This is relevant to pharmaceutical powders, particularly processes such as the handling of powdered pharmaceuticals, hard shell gelatin capsule filling, tablet and granule manufacturing, and other processes in the field of pharmaceuticals which are especially vulnerable to the impacts of such forces. Studying the possibilities that occur during the compaction of pharmacological materials is the crucial aspect of designing solid dosage forms, whereas universal testing machines or compaction simulators make systematic investigations of pharmaceuticals easier (Nguyen et al. 2020). Various parameters are measured during compaction among various researchers. Several pharmaceutical powders and formulations have had their compaction behavior evaluated using data collected from various measurements, including punch forces, die wall friction, ejection forces, change in temperature during compaction and other random variables. Among all other mathematical models, Heckel and Kawakita models show a better mathematical representation of compaction for the pharmaceutical systems within the appropriate pressure range.

1.1. Introduction to compression, compaction and consolidation

The matter or the substances present in the form of powdered solids are heterogeneous. They consist of various individual particles with different shapes and sizes in the presence of air voids. This is why it is difficult to analyze and characterize the fundamental properties of this complex powdered solid system (Lachman et al. 1986). However, with the considerable advancements in qualitative and quantitative measurements, it is possible to determine some fundamental properties of individual particles as well as bulk powdered solids from an industrial point of view. In pharmaceutical industries, the study of the physical and mechanical properties of powdered solids is necessary for the compression, compaction and consolidation of tablets.

1.2. Definition and importance in pharmaceutical manufacturing

1.2.1. Compression

Compression is the mechanical process of reduction of bulk powdered solid under applied pressure resulting in the removal of air spaces or voids. In pharmaceutical industries, compression is used for the tableting process of a particular volume of granules in a die cavity under pressure to convert it into an intact tablet. An appropriate volume of powdered solid is taken in a die cavity/mold that is compressed under pressure using an upper and a lower punch to convert it into a single matrix by removing air/gas voids, then ejected from the die/mold in the form of a tablet (Dudhat 2022).

The assessment of the compression behavior of a powdered solid is mainly dependent upon the macroscopic properties, i.e. density of solid bed and porosity. Furthermore, these properties are also affected by the punching velocity of compression, stress-strain indices and elasticity of the material after compression (Vanhoorne and Vervaet 2020).

1.2.2. Compaction

Compaction of a powdered solid is defined as the ability of powdered solid compressed to form a coherent compact solid tablet having high mechanical strength under increasing stress (Stranzinger et al. 2021; Dudhat 2022).

Compaction is considered to be one of the most important pharmaceutical unit operations. For good compaction of tablets, powdered solids must have excellent flowability and a lesser tendency of segregation. The mechanical strength of a compact solid depends upon the physical, chemical and mechanical properties of the constituent solid such as hardness, flowability, particle-particle interaction, etc., whereas lubricants and moisture content also affect the compactability of the material (Bellini 2018).

Compaction = Compression + Consolidation of two phases (solid + gas) on applying force

1.2.3. Consolidation

Consolidation is the state of powdered solid having mechanical strength due to particle-particle interactions (Mohan 2012).

There are mainly three types of mechanisms involved in the consolidation of powder solids:

• cold welding;
• fusion welding;
• recrystallization.

Figure 1.1. Different types of mechanisms involved in consolidation (prepared for this work)

1.2.3.1. Cold welding

Cold welding is one of the most widely used mechanisms for consolidation when the surface of two particles lies close enough to each other (i.e. less than 50 nm distance) having a strong attractive force, leading to strong particle-particle interaction. For this reason, cold welding increases the mechanical strength of powdered solid bed, when high compressive forces are applied.

1.2.3.2. Fusion welding

Generally, pharmaceutical powdered solids have irregular shapes and sizes, which provide a large surface area of contact (Mori et al. 2020). Therefore, a small compression force is sufficient to increase the particle-particle area of contact (Mohan 2012). If a high compression force is applied through the powdered solid bed, a considerable amount of frictional heat is produced. This heat is dissipated through the contact surfaces of solid, which causes melting of the contact area of solid particles (Sampat et al. 2022). Fusion occurs at the contact surface after the melting of irregular shapes or corners of solid particles. Melt solidifies on the removal of compressive load, which leads to a further increase in the mechanical strength of the solid bed, known as fusion bonding. There must be a possibility of deformation of the solid surface, causing the breaking and formation of new bonds, which in turn increases the consolidation effect (Wahlich 2021).

1.2.3.3. Recrystallization

The solubility of a powdered solid is directly proportional to the applied compression load. If a high compression load is applied at the point of contact of moisture and solid surface, the solubility of the solid in solution also increases.

1.2.4. Factors affecting consolidation process

1.2.4.1. Chemical properties of solids

The lattice structure and nature of the crystallinity of the powdered solid affected the solidity of the material under high compression loads (Fonteyne et al. 2015). For example, those particles having cubic lattice structures are more suitable for the tableting process than those having rhombohedral lattices.

1.2.4.2. Extent of availability of surface

The consolidation of a powdered solid is also dependent upon the extent of availability of specific surface area. When compressive force is increased to an appreciable extent, particle surfaces become fractured, which leads to an increase in surface area. Further increase in compressive force causes particles to rebond. Hence, at very high compressive force, the surface area decreases to form a solid bed of powdered solid called tablet lamination.

1.2.4.3. Effect of the presence of contamination on the surface of the particle

The consolidation process is also affected due to the presence of surface contaminants. Surface contamination plays a vital role in the initial bond formation between powdered solid particles. For example, the presence of diluents, and lubricants on the surface of pharmaceutical powder aims to create a weak bond between them. This causes continuous coating on the tableting mass. Therefore, if contamination occurs at a larger extent on the surface of particles, it results in the formation of weaker tablets (Arshad et al. 2021).

1.2.4.4. Interparticle attractive forces

The interparticle attractive forces have a direct influence on the consolidation of the powdered solid bed. When a small compressive load is applied, molecular or electrostatic forces exist between individual particles. Van der Waals forces become predominant at an intersurface distance of 100 nm, which tends to form agglomerates. This agglomeration leads to an increase in the air spaces of the solid bed. The tablet then formed has low mechanical strength and is not stabilized. This may lead to cracking in the internal structure.

Therefore, the consolidation behavior of powdered solid can be controlled by internal (Van der Waals) as well as external forces (i.e. elasticity and plasticity). Consolidation gives rise to a decrease in air space, hence preventing the breakdown of a tablet (Kengar et al. 2019).

1.3. Powder properties and their characterization

1.3.1. Characteristics of pharmaceutical powders, flowability, particle size and distribution

Figure 1.2. Derived properties of powder (prepared for this work)

While considering the tableting process of the...