Direct compression method diluent

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. 

Native starches are used as disintegrants, diluents, and wet binders. However, their poor flow and high lubricant sensitivity make them less favorable in direct compression. Different chemical, mechanical, and physical modifications of native starches have been used to improve both their direct compression and controlled-release properties (Sanghvi, 1993 van Aerde and Remon, 1988). Schinzinger and Schmidt (2005) used potato starch as an excipient and compared its granulating behavior with a-lactose-monohydrate and di-calcium phosphate anhydrous in a laboratory fluidized bed granulator using statistical methods. 

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... 

One of the difficulties that beset the product developer is the lack of meaningful tests by which excipients (including direct compression diluents) can be assessed. This has led to the development of the so-called functionality tests. Some functionality tests that have been suggested (e.g., particle size, surface area) are in fact physical test methods being carried out under closely defined conditions. The relation of such a test to the actual function of the excipient needs to be established. After this link has been made, a more suitable title for these tests might be functionality-related tests. ... 

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. ... 

---