Direct compression method tablet diluents

If a major component of the formulation such as the diluent were to possess the necessary degrees of fluidity and compressibility, granulation would be unnecessary. This is the basis of the direct compression method of tablet manufacture. 

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... 

A faulty batch of tablets can sometimes be recovered by grinding up the tablets and recompressing them, a process which is known as reworking and is analogous to the dry granulation method of tablet manufacture. This can sometimes cause problems with a direct compression formulation. Many direct compression diluent particles are in the form of aggregates, e.g., spray-dried lactose is composed of small crystals of lactose embedded in amorphous lactose. If these aggregates are compressed, their structure may be broken down to such an extent that subsequent recompression will result in impaired tablet quality. 

The technique of Malkowska and Khan, " used as described before to determine the capacity of a direct compression diluent, was originally developed as a method of expressing the ability of a formulation to be reworked. Referring to Fig. 2, the upper curve represents the strength of tablets prepared without reworking and the lower curve is the strength of reworked tablets. The reworking index is calculated from the ratio of the areas under the curves as described previously. 

Sorbitol can exist in four crystalline forms. Guyot-Hermann, Leblanc, and Draguet-Brugmans compared 11 commercially available varieties of sorbitol, and found three of these four forms to be present. y-Sorbitol was found to be the most useful as a tablet diluent. The method of manufacture has also been shown to affect tabletting properties, differences being attributed to variations in particle shape and surface properties. Spray-dried varieties of sorbitol are available as direct compression diluents which are claimed to have overcome problems associated with the different crystalline forms. ... 

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