Stability of Medicines Flashcards
What is a lyophobic system?
-Systems that have a poor interaction with the solvent
What law governs sedimentation?
-Stokes law
What is homogenous stability?
-Even disposal of molecules
What is non-homogenous stability?
-Molecules are not dispersed evenly throughout the system
How can sedimentation be prevented?
-By adding a co-suspension (specifically formulated phospholipid particles)
What is aggregation?
-Particles come together in groups
What is coagulation?
-particles that are closely aggregated and difficult to re-disperse
What is sedimentation?
-Process of settling or being deposited as a sediment
What is caking ?
-Deflocculated particles form cakes which are difficult to re-disperse
What is Ostwald ripening?
-Dissolution of small particles and re-disposition of dissolved species on the surfaces of larger crystals
What factors can effect stability?
-kinetic properties
-size/shape
-electrical properties
What is Brownain motion?
-Random movement of particles
What does fick’s first law determine?
-Diffusion rate
What does stokes-einstein equation determine?
-Diffusion coefficient
What is the rate of sedimentation dependent on?
-The combined forces of gravity and drag
What is viscosity ?
-Resistance to flow under an applied stress
What happens to sedimentation rate when viscosity is increased?
-Decrease
What is viscosity related to?
-Molecular weight of suspended particles and suspending agents
What factors influence the rheology of suspensions?
-High volume fractions
-Particle size
-Particle distribution
-Particle shape
-Electrostatic interactions
-Steric hindrance
How can sedimentation be prevented?
-Form smaller particles
-Decreases the density difference between the two phases
-Increase viscosity of the continuous phase
How do most surfaces acquire charge?
-ion dissolution
-ionisation
What is Zeta potential ?
-Magnitude and type (+/-) of the electrical potential at the slipping plane
What does a low (0 to 5 mV) zeta potential mean?
-Prone to aggregate
What does a high (>30mV) zeta potential mean?
-Tend to remain dispersed
What factors affect zeta potential?
-Ion concentration
-pH of continuous phase
How does ion concentration effect zeta potential ?
-Charge of ions determines magnitude
How does pH of continuous phase effect zeta potential ?
-Alters the ionisation of ionic species in the continuous phase and the surface charge of ionisable groups
What is the DVLO theory?
-a quantitive approach to the stability of lyophobic systems that assumes the only interactions involved for Van Der Waals and electrostatic repulsive forces
If there is a low energy of repulsion what happens to the particles?
-Possible flocculation
If there is a high energy of repulsion what happens to the particles?
-Will likely remain dispersed
What does Va stand for?
-Van der Waals forces of attraction
What does vR stand for?
-Electrical repulsion
What happens when Va is high?
-Strong attraction - coagulation
What happens when Va is closer to the origin?
-Weak attraction will mean flaws are formed
What happens when Vr is closer to the origin?
-Weak repulsion will mean flags are formed
How does an emulsion instability occur?
-Phase intervention
-creaming
-flocculation
-coalescence
-Ostwold ripening
What do droplets do in a stable emulsion?
-Retain their initial character and remain uniformly distributed throughout the continuous phase
What is phase inversion?
-Oil-in-water is stabilised by co-surfactant charge on emulsion is reduced through addition of ions via buffer or drug so droplets will come together
-Once in contact, interfacial surfactant film re-aligns forming water-in-oil
What is creaming?
-Due to the density difference between oil and water, oil droplets tend to concentrate at the top of the emulsion
How can creaming be avoided?
-Increases the oil density or viscosity of the emulsion
What is flocculation in an emulsion?
-When two or more emulsion droplets aggregate without losing their individual identity
What is coalesnce?
-Occurs when two or more droplets collide and form one larger droplet and is irreversible
What causes coalescence?
-Surfactant type
-Concentration of surfactant
-pH
-Temperature
What factors cause van der Waals forces to vary?
-Distance between pairs of atoms or molecules
What type of surfactants does DVLO theory apply to?
-Ionic
Why doesn’t DVLO theory apply to non-ionic surfactants ?
-No electrostatic charge is present so the charge on the droplet is neutral
What are steric effects?
-When two particles comes into contact a polymer chain starts to overlap leading to a loss in freedom/entropy. This is thermodynamically unfavourable and forces the droplets apart
What are salvation forces?
-The two particles come into contact and polymer chains overlap forming a concentrated polymer solution inducing an osmotic gradient in the solution. Water enters the concentrated region in an attempt to dilute it and on doing so forces the polymer chains and droplets apart
What are the 4 types of forces in emulsions?
-Van Der Waals (+)
-Electrostatic (-)
-Steric (-)
-Solvation (-)
What forces are most important in charged colloids?
-Van der Waals
-Electrostatic
What forces are most important in uncharged colloids?
-Van der Waals
-steric
-Solvation
What emulsions achieve best stability?
-Emulsions where electrostatic, steric and salvation forces can be present
What is stability?
-The capacity of a product to remain within specifications to ensure potency, quality or purity
What can instability cause?
-Inconsistent dose
-Undesired change in performance
-Changes in physical appearance of the dosage form
-Product failures
What is chemical degradation?
-Decomposition of chemical moiety due to effects of moisture, oxygen, light and heat which can result in the loss of active drug
What is the physical degradation?
-Formulation-specific : caking in suspensions, phase separation in emulsions which can cause hardness and brittleness of tablets
What is microbial degradation?
-Microbial contamination: metabolism of drug molecule or physical spoilage of dosage form that can lead to infection
What chemical degradation reactions occur?
-Hydrolysis
-Oxidation
-Photodegradation
-Polymerisation and dimerisation
Why is hydrolysis the most common chemical degradation?
-Water is present in many pharmaceuticals and carboxylic acid derivatives (esters and amines) are also common
How is hydrolysis reduced to prevent chemical degradation?
-Dry formulations
-Adjusting pH to maximise stability in aqueous forms
-Storage temperature
-coating
-Choice of packaging
How is the rate of hydrolysis reduced to prevent chemical degradation?
-Complexation
-Surfactants
How does oxidation break down drugs?
-Removes H+, loss of e- and addition of O usually through free radicals
What are free radicals?
-Highly reactive chemicals unpaired electrons
What is auto-oxidation ?
-The formation of peroxyl radicals which initiates and propagates auto-oxidation in the propagation step
What are the ways you can overcome auto-oxidation?
-Remove initiators
-Excludes O2
-Add free-radicals scavengers
How does removing initiators reduce auto-oxidation?
-Chelation of trace metals with chelating agents; EDTA, citric acid and tartaric acid
How can you exclude O2 to prevent auto-oxidation?
-Sparge liquids with inert gases eg nitrogen to displace oxygen
How does adding free radicals prevent auto-oxidation?
-Butylted hydroxytoluene is more readily oxidised than oils
