The vast majority of drugs, when isolated, exist as crystalline or amorphous solids. Subsequently, they may be either milled (comminuted) and/or admixed with other inactive solids (excipients) and finally filled into capsules or compacted to form tablets. The processes of comminution and compaction involve subjecting the materials to stresses that cause them to undergo deformation. The reaction of the material to the deformation stress, od, is dependent on both the mode of deformation and the mechanical properties of the material.

where E is the Young's modulus of elasticity of the material and e is the deformation strain.

(b) For plastic deformation

where oy is the yield stress of the material.

(c) For brittle fracture


<d where KIC is the critical stress intensity factor of the material (an indication of the stress required to produce catastrophic crack propagation), d is the particle size (diameter) and A is a constant depending on the geometry


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Brittle-ductile transition

Brittle-ductile transition c o n E o

Particle size (diameter)

fig. 1 Schematic diagram showing the effect of particle size on the deformation stress for materials that undergo brittle fracture and/or plastic deformation.

and stress application. For compression of rectangular samples with large cracks A = V32/3 or 3.27 (Kendall, 1978) but for other geometries A varies between 50 and 1 (Puttick, 1980).

It is evident from the equations and Fig. 1 that large particles will tend to crack because the stress required for brittle fracture will be less than that needed for plastic flow and vice versa for very small particles. The transition from brittle to ductile behaviour will occur at a critical size, dcrit, where the two stresses will be equal, i.e.

Application of equation 4 will be discussed later in the chapter.

It is evident from the discussion above that in order to be able to predict the comminution and/or compaction behaviour of a material it is essential that methods be derived to measure for powdered materials:

(a) The Young's modulus of elasticity (E)

(b) The yield stress (ay) - this is directly related to the indentation hardness, H, since for a plastic material:

(c) The critical stress intensity factor (K,c) - this is directly related to the fracture toughness, R, since for plane stress:

In this chapter various methods that have been specifically applied to pharmaceutical materials are reviewed and critically examined.

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