Tablet particle behavior

All tablet manufacture can be regarded as the application of pressure to a population of particles enclosed in a confined space. An understanding of particle behavior under such conditions is therefore the key to understanding the formation and properties of tablets. 

In 1991, Bonny and Leuenberger [40] explained the changes in dissolution kinetics of a matrix controlled-release system over the whole range of drug loadings on the basis of percolation theory. For this purpose, the tablet was considered a disordered system whose particles are distributed at random. These authors derived a model for the estimation of the drug percolation thresholds from the diffusion behavior. 

The work conducted by Gustafsson et al. [19] evaluated the particle properties and solid-state characteristics of two different brands of microcrystalline cellulose (Avicel PH101 and a brand obtained from the alga Cladophora sp.) and related the compaction behavior to the properties of the tablets. The difference in fibril dimension and, thereby, the fibril surface area of the two celluloses were shown to be the primary factor in determining their properties and behavior. 

Hersey, J.A. Rees, J.E. The effect of particle size on the consohdation of powders during compaction, proceedings from the 2nd, Particle Size Analysis Conference Society for Analytical Chemistry Bradford, UK, 1970, 33-41. York, P. Pilpel, N. The tensile strength and compression behavior of lactose, four fatty acids and their mixtures in relation to tableting. J. Pharm. Pharmacol. 1973, 25 (12 suppl), IP-llP. 

Tablets. SEM was widely used to investigate the structure of tablets. An excellent review is presented by Hess. " Imaging of tablets is a useful tool to demonstrate differences in compression behavior of substances. Fig. 24 shows an example where the plastically deforming spray-dried sorbitol instant was compressed together with the more brittle ascorbic acid in one tablet. At low compressional force of 5 kN for a 10 mm tablet, the rectangular ascorbic acid crystals as well as the partially deformed sorbitol particles are visible (Fig. 24A). In Figs. 24A and B, the surfaces of two tablets compressed at 5 kN and 30 kN are compared. At higher compressional forces, a uniform, flat, and smooth tablet surface is formed, but within this surface a single unchanged ascorbic acid crystal could be detected. Observation of a broken tablet (Fig. 24C), which was prepared at a high compressional force of 30 kN, reveals that the ascorbic acid crystal is totally fixed within a matrix of plastically...

This type of material behavior is very important in lableting especially when materials like MCC are reworked. For example, it is hypothesized that when roller compacting MCC if the material is over compressed when going through the rollers that it will work harden and not deform as readily when compacted into tablets. The reduced compactibility results in less contact between the particles, and thus, weaker tablets, and in fact this type of behavior is often observed. 

In one study, the formulation efficiency of several direct compression materials was evaluated using instrumented press methodology. It was found that subtle changes in the structure of the component particles could lead to observation of significantly different behaviors upon compression. The tablet hardness and compressibility of differently sourced sucrose materials, obtained at comparable compressional forces, was found to vary significantly with the source of the compound. 

The compressional behavior of four polymorphs of mannitol (the a, P, and 5 forms, as well as one unidentified phase) has been studied [57]. It was found that the compressibility of the a-phase is superior, and fortunately this phase is the major form in most commercial products. The particle shape was found to exert an influence upon the compressibility properties granulated powders show better behavior than native crystalline powders. It was reported that no polymorphic transitions took place under the compression stresses used during the tableting process. 

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