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