PAC3241 Study Guide - Final Guide: Viscosity, Bioavailability, Sugar Substitute

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Rationale behind of addition of buffering or isotonicity adjusting salts may alter the stability of
lyophilic and lyophobic colloidal dispersed systems:
In both lyophilic and lyophobic colloidal dispersed systems, addition of buffering or isotonicity
adjusting salts would increase the concentration of ions in the solution. This could decrease zeta
potential (and surface charge) which could lead to compression of EDL thickness with less repulsion
between particles. As a result, the particles come closer to one another and the attractive Van der
Waals’ forces will dominate which promotes aggregation. On a side point, a high valency counterion
(e.g. trivalent ion like Al3+) will cause the same extent of particle aggregation at a lower concentration
as needed by a low valency counterion (e.g. monovalent ion like Na+) according to Schulze-Hardy
Rule.
NOTE: Colouring agents are polyvalent substances which can also decrease zeta potential and lead
to EDL compression.
EXTRA: With respect to lyophilic colloidal dispersed system only, the addition of isotonicity adjusting
salts such as NaCl will result in salting out where the ions compete for the water of hydration and
dehydrate the particles in dispersed phase. /competitive desolvation - for lyophilic system
DLVO theory:
DLVO theory helps explain the basis for particle aggregation such that the total energy of interaction
is the sum of both attraction and repulsive forces. DLVO graph describes the interaction between two
particles with reference to their total potential energy and separation/interparticle distance (H).
High concentration and valency of ions which results in EDL compression causes the interparticle
distance (H) to be extremely small. As a result, the particles go into primary minimum region in which
the attractive forces are greater than the repulsive forces. In other words, the particles are strongly
held by attractive Van der Waals’ forces, leading to aggregation and irreversible association (i.e.
caking).
When individual particle is present in the dispersion system, the particles are in the primary maximum
region where the repulsive forces are dominating. The maximum energy barrier prevents the particles
from coming into contact with each other, resulting in minimal particle association. Particles with high
zeta potential causes high repulsion between adjacent similarly charged particles, forming a
deflocculated system. The deflocculated system is only advantageous for particles with diameter
smaller or equal to 0.5 µm which are not subjected to gravitational movement. On the other hand,
particles with diameter greater than 0.5 µm would eventually settle, sediment and cake, thereby
returning to primary minimum region (i.e. an unstable system).
When the maximum energy barrier is too high to overcome, the colloid particles may stay in the
secondary. This is shown by long interparticle distance (H) which results in greater reduction in
repulsive forces. Therefore, particles aggregate loosely to one another by weak attractive Van der
Waals forces (i.e. weaker than the primary minimum region), forming a flocculated system. This is
particularly useful in maintaining suspension (which generally contains particle r > 1 µm that is subject
to gravitational movement) stability as the flocculated system is easy to re-disperse upon shaking.
Difference between flocculated vs deflocculated system and their applications in
pharmaceutical dispersions:
Flocculated system has high sedimentation volume (F) (i.e 1) whereas deflocculated system has
low sedimentation volume (i.e ≤ 0.5). Flocculated suspension do not cake upon particles settling and it
is easy to redisperse with shaking.Therefore, flocculated system is pharmaceutically acceptable
system and it is best system for long storage time of suspensions. It will not settle even after adding
more solvent. Deflocculated suspension system often form hard cakes upon sedimentation due to
close packing of the sediment and it is irreversible upon shaking.
We want flocculated system.
Flocculation can be induced by:
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