Compressible tablet excipients, lactose

Whiteman, M. Yarwood, R.J. The evaluation of six 38. lactose-based materials as direct compression tablet excipients. Drug Dev. Ind. Pharm. 1988,14 (8), 1023-1040. 

Different localized levels of molecular order can coexist in some pharmaceutical materials, giving rise to the occurrence of partially crystalline (and partially amorphous ) systems. In most cases, the properties of such materials (e.g., density) are intermediate to those of the 100% amorphous and 100% crystalline samples. By deliberately varying the level of crystallinity in such systems, their properties can be customized for a particular purpose. An example of this is with the tableting excipients microcrystalline cellulose and spray-dried lactose, which have had their compression characteristics optimized by manipulating their amorphous content. The properties of partially crystalline materials may be approximated in many instances by making physical mixtures of the totally amorphous and crystalline samples. This is known as the two-state model for partially crystalline systems.However, such experiments should be undertaken with caution as the mixed two-state material can sometimes have significantly different properties from the partially crystalline material that is manufactured directly (the real one-state system). ... 

Chitosan (molecular weight, 19-400 kDa degree of deacetylation, 75-98%) has been evaluated as a directly compressible vehicle for tablets, but has found limited utility due to the lack of good flow properties and compressibility. The influence of excipient (lactose, sodium lauryl sulfate, sodium alginate, hydroxypropyl methyl... 

The availabihty of spray-dried lactose, microcrystaUine cellulose, and other excipients allows for the use of granular rather than powdered phases. This eliminates some of the problems of particle segregation according to size (demixing) and even flow to the die. Direct compression eventually may be the preferred method of tablet preparation. 

The range of compression pressures to prepare tableting indices compacts is shown in Table 3 with each considered moderate relative to other excipients such as lactose, mannitol, and calcium phosphate dibasic. Avicel PH302 required considerably less pressure than PH102 and PH105, and thus shows greater ease of compression. Their moderate compressibility indicates that a fairly substantial pressure was required to achieve the SF. The rank order of each excipient by the tableting indices mechanical properties is provided in Table 4. 

The first direct compression excipient, spray-dried lactose, was introduced in the early 1960s as a filler specifically designed for direct compression processes. Over many years, more direct compression API and excipients, especially diluents and binders, were developed. Since these are now commercially available, design of direct compression formulations is readily possible. However, despite the simplicity of the direct compression process, the pharmaceutical industry still produces most tablets by wet granulation methods.1... 

The impurity peak at RRT 3.4 was observed in all samples exposed to accelerated conditions. Structural identification of this peak could not be established since this component did not show any response in the mass spectral analysis. The presence of this peak in large amounts in both active and placebo tablets lead to the conclusion that the late eluting impurity observed at RRT 3.4 was indeed a degradation product of one or more of the excipient components present in the tablets. Because of the large amounts of this impurity in the samples, a study using the individual excipients was conducted to identify the source of this degradant. The study lead to the conclusion that the excipients exposed to accelerated conditions in powder form did not produce the degradation product. However, when the same excipients were compressed into pellets and exposed to the same conditions, lactose, microcrystaUine cellulose and croscarmellose sodium compacts showed the presence of the peak at RRT 3.4. 

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