Appendix V Q. Density of Solids
The density of solids corresponds to their average mass per unit volume and typically is expressed in grams per cubic centimetre (g/cm3) although the International Unit is the kilogram per cubic metre (1 g/cm3 = 1000 kg/m3).
Unlike gases and liquids whose density depends only on temperature and pressure, the density of a solid also depends on its assembly and therefore varies with the crystal structure and degree of crystallinity.
When a solid is amorphous or partially amorphous, its density may further depend upon the history of preparation, treatment and storage.
Therefore, unlike fluids, the densities of 2 chemically equivalent solids may be different, and this difference reflects a difference in solid-state structure. The density of constituent particles is an important physical characteristic of pharmaceutical powders.
The density of a solid particle can assume different values depending on the method used to measure the volume of the particle. It is useful to distinguish 3 levels of expression of density:
true DENSITY
The true density of a substance is the ratio of the mass to the volume of the unit cell, exclusive of all voids that are not a fundamental part of the molecular packing arrangement. It is an intrinsic property of the specified crystal structure of substance, and hence should be independent of the method of determination. The true density is determined by calculation.
It is obtained using crystallographic data (volume and composition of the unit cell) from, for example, X-ray diffraction data, either on a single crystal or by refinement of the crystalline structure from X-ray powder diffraction data.
PARTICLE DENSITY
The particle density takes into account both the true density and the intraparticulate porosity (sealed and/or experimentally non-accessible open pores). Thus, particle density depends on the value of the volume determined, which in turn depends on the method of measurement. The particle density can be determined using one of the 2 following methods.
The gas pycnometric density is determined by measuring the volume occupied by a known mass of powder, which is equivalent to the volume of gas displaced by the powder using a gas displacement pycnometer (2.9.23). In gas pycnometric density measurements, the volume determined excludes the volume occupied by open pores; however, it includes the volume occupied by sealed pores or pores inaccessible to the gas. Due to the high diffusivity of helium, which is the preferred choice of gas, most open pores are accessible to the gas. Therefore, the gas pycnometric density of a finely milled powder is generally not very different from the true density. Hence, this density is the best estimate of the true density of an amorphous or partially crystalline sample and is therefore widely applicable for processed pharmaceutical powder samples.
The mercury porosimeter density is also called granular density. With this method the volume determined includes the volume occupied by sealed pores or pores inaccessible to mercury; however, it includes the volume only from open pores smaller than some size limit. This pore-size limit or minimal access diameter depends on the maximal mercury intrusion pressure applied during the measurement, and under normal operating pressures the mercury does not penetrate the finest pores accessible to helium. Various granular densities can be obtained from one sample since, for each applied mercury intrusion pressure, a density can be determined that corresponds to the pore-size limit at that pressure.
BULK AND TAPPED DENSITY
The bulk density of a powder includes the contribution of interparticulate void volume. Hence, the bulk density depends on both the density of powder particles and the spatial arrangement of particles in the powder bed.
The bulk density of a powder is often very difficult to measure with good reproducibility since the slightest disturbance of the bed may result in a new density. Thus, it is essential in reporting bulk density to specify how the determination was made.
The bulk density and the tapped density are determined as mentioned in chapter 2.9.34. Bulk density and tapped density.