physical pharmacy

1. SAMIA GHANI
M.Phil Pharmaceutics

2. Crystallization (Definition)
• Crystallization is the spontaneous
arrangement of the particles into a
repetitative orderly, i.e., regular
geometric patterns OR
• Crystallization is also a chemical solid-
liquid separation technique in which mass
transfer of a solute from the liquid solution
to a pure solid crystalline phase occurs.

3. •A crystal can be defined as a solid particle, which
is formed by the solidification (crystallization)
process (under suitable environment) in which
structural units are arranged by a fixed geometric
pattern or lattice.

4. •Crystal lattice is defined as an orderly
arrangement of particles in three – dimensional
space. The Three dimensional arrangement of
particle in a crystal is also known as space lattice
The smallest geometric portion, which repeat to
build up the whole Crystal, is called a unit cell.
•A crystal is bounded by plane surface called faces
The angle between the two perpendicular to the
intersecting faces is termed as the axial angle
Axial length can be defined as the distance
between the centre of two atoms.

5. •All crystals are constructed from repeating units
called unit cells. All unit cells in a specific crystal
are the same size and contain the same number of
molecules or ions arranged in the same way.
•There are seven primitive unit cells;
•cubic, hexagonal, trigonal(rhombohedral),
tetragonal, orthorhombic, monoclinic and
triclinic.

8. In chemical engineering crystallization occurs in a
crystallizer. Crystallization is therefore an aspect
of precipitation, obtained through a variation of
the solubility conditions of the solute in
the solvent, as compared to precipitation due to
chemical reaction.
There are two major events in the process of
crystallization
a. Nucleation
b. Crystal growth

9. A step where the solute molecules dispersed in
the solvent start to form clusters together.
These clusters become stable under the current
operating conditions.
However, when the clusters are not stable they
redissolve. Therefore, the clusters need to reach a
critical size in order to become stable nuclei.
It is at the stage of nucleation that the atoms
arrange in a defined and periodic manner that
defines the crystal growth.

10. •Nucleation is the initiation of a phase change in a
small region, such as the formation of a solid
crystal from a liquid solution.
•Total nucleation is the sum effect of two
categories of nucleation – primary and secondary.

11. Primary nucleation is the initial formation of a
crystal where there are no other crystals present
or where, if there are crystals present in the
system, they do not have any influence on the
process
Secondary Nucleation is attributable to fluid
shear, the other due to collisions between already
existing crystals with either a solid surface of the
crystallizer or with other crystals themselves.

12. •Once the first small crystal, the nucleus, forms
it acts as a convergence point for molecules of
solute touching – or adjacent to – the crystal so
that it increases its own dimension in successive
layers.
•The pattern of growth resembles the rings of an
onion, as shown in the picture, where each
colour indicates the same mass of solute; this
mass creates increasingly thin layers due to the
increasing surface area of the growing crystal.

15. In crystallization Processes nuclei formation
should be under control, since the number of
nuclei will control the size of the crystal.
Large crystals may be obtained as a result of slow
cooling of solutions.
Nucleation may be inhibited by the presence of
impurities, especially if of high molecular weight
in the solution.

16. 1. The applications of the crystallization
technique in the pharmaceutical industry as a
purification and separation process for the
isolation and synthesis of pure active
pharmaceutical ingredients (API)
2. Crystallization is practiced on all scales: from
the isolation of the first milligrams of a newly
synthesized substance in the research
laboratory to isolating products on the mulit-
million tone scale in industry.

17. •Bentley Textbook of Pharmaceutics, Eighth edition,
edited by E.A Rawlins, chapter 25 and 26, page
347-350, 351.
•Pharmaceutical Practice, Fourth Edition, edited by
Arthur J. Winfield, Judith Rees and Smith, Chapter
25.
•Handbook of Pharmacy, Embracing the theory and
the practice of pharmacy and Art of Dispensing
(1894), page 352.