Stability Flashcards
What interaction do lyophobic systems have with the solvent?
Poor
What physical stability do suspensions have?
Coarse
Why are large particles sedimenting problematic?
Not mixed evenly
Uneven distribution
What governs sedimentation, enabling redispertion?
Stokes’ Law
What does homogeneous dose mean?
Mixed dose
What does heterogeneous dose mean?
Not a well dispersed dose
What are the main instability phenomenas of macro particles?
Aggregation
Coagulation
Flocculations
Sedimentation
Caking
Ostwald ripening
What is aggregation?
Particles in groups
What is coagulation?
Closely aggregated and difficult to redisperse
What is flocculation?
Aggregates have an open structure with particles a small distance apart, attracted by a weak force to form flocs or flakes
What is sedimentation?
Process of settling or being deposited as a sediment
What is caking?
Defloculatted particles form cakes which can be difficult to re-suspend
What is Ostwald ripening?
Dissolution of small crystals
What does physical instability result in?
Poor dosing
What are the main factors affecting stability?
Kinetic properties
Size/shape
Electrical properties
What does the brownian motion and diffusion mean?
Particles diffuse from a high concentration
What law is diffusion rate based on?
Fick’s first law
What is the diffusion rate equation?
dm=-DA dc
dt. dx
What does dm over dt mean?
Mass of substances
What does D mean in Fick’s first law?
Diffusion coefficient
What does A mean in Fick’s first law?
Area
What does dc over dx mean in Fick’s first law?
Concentration gradient
What does viscosity relate to?
Molecular weight of suspended particles/suspending agents
How do we prevent sedimentation?
Form smaller particles
Decrease the density difference
What are the names of each layer in the electrical double layer of ions?
Stern layer
Diffuse layer
What does zeta potential stand for?
Magnitude and type of the electrical potential at the slipping plane
What does low zeta potential mean?
Prone to aggregate
What does high zeta potential mean?
Tend to remain dispersed
What are the factors affecting zeta potential?
Ion concentration - determines magnitude
pH of continuous phase- alters the ionisation
What does the DLVO graph show?
Quantitative approach to the stability of lyophobic systems
What does the DLVO graph assume?
That the only interactions involved are van Der walls (VA) and electrostatic repulsive forces (VR)
What is the equation for DLVO?
VT=VA+VR
What is the instability phenomena?
Not redispersable
What is emulsion stability?
Droplets can retain their initial character and remain uniformly distributed throughout the continuous phase.
When can emulsion stability occur?
Phase inversion
Creaming
Flocculation
Coalescence
Ostwald ripening
What is phase inversion?
Oil in water emulsion stabilised by ionic surfactant/ co-surfactant
What is creaming?
Different density between oil and water, the oil droplets tend to concentrate at the top of the emulsion.
What is flocculation?
When two or more emulsion droplets aggregate without losing their individual identity
What is coalescence?
When two or more droplets collide me form one larger droplet and is irreversible
What is Ostwald ripening?
Collision between two droplets may cause one bigger droplet and one smaller droplet
What does the van der waals forces in the DLVO graph explain?
Explains why some colloidal particles aggregate
Eva use energy attraction varies with the distance between the pairs of atoms or molecules or neighbouring particles with the inverse of the 6th power.
A=1
H*6
What does the electrostatic repulsive forces explain in the DLVO graph?
Explains why some colloidal particles stay separated
Arrives from the interaction of the electronic double layers surrounding pairs of particles
Depends on zeta potential
What does low zeta potential mean?
Flocculated
What does high zeta potential mean?
Stable
What are the factors in the secondary minimum on the DLVO graph?
Forces of attraction are weak
Flocculation
Minimum attraction at large distances of separation
What are the factors of the primary maximum on the DLVO graph?
Particles come closer so there are some repulsion
Height of this repulsion determines the stability of the system (vmax)
What are the factors of the primary minimum in the DLVO graph?
At close approach van der waals forces always dominate over repulsive electrostatic forces
Coagulation that’s irreversible
What are the two ways non-ionic surfactants interact with each other?
Entropic (steric) effects
Osmotic (salvation) forces
What happens when entropic effects happens?
The polymer chains on non-ionic surfactants start to overlap
Which leads to a loss of freedom of motion
This situation is thermodynamically unfavourable and forces the droplets apart again
What happens when there are osmotic forces in non-ionic surfactants?
When two particles come in close contact the polymer chain starts to overlap effectively, leading to concentrated polymer solution
Induces osmotic gradient
Water enters the concentrated region and forces the polymer chains apart.
What are the 4 main types of forces?
Van der waals (attractive)
Electrostatic (repulsive)
Steric forces (repulsive)
Salvation forces (repulsive)
What types of forces do charged colloids use?
Van der waals
Electrostatic
What types of forces do uncharged colloids use?
Van der waals
Steric
Solvation
What does stability stand for in medicines?
Capacity of a product to remain within specifications to ensure potency, quality or purity
What are the 3 types of degradation of medicines?
Chemical degradation
Physical degradation
Microbial degradation
What is chemical degradation?
Decomposition of chemical moiety
What is physical degradation?
Formulation specific
E.g. caking is suspensions, phase separations, hardness and brittleness in tablets
What is microbial degradation?
Microbial contamination
What can drug instability cause?
Inconsistent dosing
Undesired change in performance
Changes in physical appearance
Product failures
What are the 4 chemical degradation reactions?
Hydrolysis
Oxidation
Photochemical degradation
Polymerisation
How do we reduce hydrolysis reaction for chemical degradation?
Dry formulations
Adjusting pH to maximum stability
Storage temperature
Coating
Choice of packaging
How can we reduce oxidation reaction in chemical degradation?
Remove initiators
Exclude O2
Add free radical scavengers
How do we reduce photochemical degradation in chemical degradation?
Hide from light
Black out containers/ packaging
How can we reduce polymerisation reaction in chemical degradation?
Hide from UV
What are the different reactions in chemical degradation classified?
Zero order+ pseudo zero order
First order+ pseudo first order
Second order reactions
What is a zero order reaction?
The rate of degradation of A is independent of the concentration of the reactants
[A]t= [A]o -kt
What are first order reactions?
The rate of degradation of A is directly proportional to its contraction [A]
In[A]t=In [A]o-kt
What are pseudo zero order reactions?
Observed rate constant is an expression for a zero order reaction.
What are second order reactions?
The rate of degradation of A is directly proportional to its concentration and the concentration of the reactant B
1. =. 1. +kt
[A]t. [A]o
What are pseudo first order reactions?
Observed rate constant is an expression for a first order reaction
How much degradation is allowed?
5-10% loss over 5 years
