Particle Properties of Powders

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Chapter: Pharmaceutical Engineering: Powders

The structure of particles may be characterized in terms of crystal system and crystal habit.



To understand particle properties it is important to consider their origins. Particles may be produced by different processes that can be regarded as con-structive or destructive (Hickey, 1993). Constructive methods include crystalli-zation, precipitation, and condensation, and destructive methods include milling and spray drying.

The most common methods of bulk manufacture are crystallization and precipitation from saturated solutions. These solutions are saturated by exceeding the solubility limit in one of several ways (Martin, 1993). Adding excess solid in the form of nucleating crystals results in crystallization from saturated solution. This can be controlled by reducing the temperature of the solution, thereby reducing solubility. For products that can be melted at relatively low temperatures, heating and cooling can be used to invoke a controlled crystallization. The addition of a cosolvent with different capacity to dissolve the solute may also be used to reduce the solubility and result in precipitation. In the extreme, a chemical reaction or complexation occurs to produce a precipitate (e.g., amine-phosphate/sulfate interactions; Fung, 1990). Condensation from vapors is a technical possibility and has been employed for aerosol products (Pillai et al., 1993), but has little potential as a bulk manufacturing process.

Milling (Carstensen, 1993) and spray drying (Masters, 1991) may be described as destructive methods since they take bulk solid or liquid and increase the surface area by significant input of energy, thereby producing small discrete particles or droplets. The droplets produced by spraying may then be dried to produce particles of pure solute. A variety of mills are available dis-tinguished by their capacity to introduce energy into the powder. Spray dryers are available that may be utilized to produce powders from aqueous or non-aqueous solutions (Sacchetti and Van Oort, 2006).


The structure of particles may be characterized in terms of crystal system and crystal habit. The crystal system can be defined by the lattice group spacing and bond angles in three dimensions. Consequently, in the simplest form, a crystal may be described by the distance between planes of atoms or molecules in three dimensions (a, b, and c) and by the angles between these planes (α, β, and γ), where each angle is opposite the equivalent dimension (e.g., α opposite a). These angles and distances are determined by X-ray diffraction utilizing Bragg’s law (Mullin, 1993). Crystals may be considered as polygons wherein the numbers of faces, edges, and vertices are defined by Euler’s law. There are more than 200 possible permutations of crystal system based on this definition. In practice, each of these geometries can be classified into seven specific categories of crystal system: cubic, monoclinic, triclinic, hexagonal, trigonal, orthorhombic, and tetragonal.

Once the molecular structure of crystals has been established, the manner in which crystal growth occurs from solution is dictated by inhibition in any of the three dimensions. Inhibition of growth occurs because of differences in surface free energy or surface energy density. These differences may be brought about by regions of different polarity at the surface, charge density at the sur-face, the orientation of charged side groups on the molecules, the location of solvent at the interface, or the adsorption of other solute molecules (e.g., surfactant). Crystal growth gives rise to particles of different crystal habit. It is important to recognize that different crystal habits, or superficial appearance, do not imply different lattice group spacing, as defined by crystal system. Also it is possible that any of the methods of production may result in particles that have no regular structure or specific orientation of molecules, which are, by defini-tion, amorphous.


Properties dictated by the method of manufacture include particle size and distribution, shape, specific surface area, true density, tensile strength, melting point, and polymorphic form. Arising from these fundamental physicochemical properties are other properties such as solubility and dissolution rate.

Polymorphism, or the ability of crystals to exhibit different crystal lattice spacings under different conditions (usually of temperature or moisture con-tent), can be evaluated by thermal techniques. Differential scanning calorimetry may be used to determine the energy requirements for rearranging molecules in the lattice as they convert from one form to another. This difference between polymorphic forms of the same substance can also be detected by assessing their solubility characteristics.

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