Pharmaceutics - Prof Guy Flashcards
What is pseudoplastic flow?
As sheering stress increases, the polymer molecules align themselves more orderly… meaning that as more pressure is added… it becomes less viscous
Viscosity decreasing can also be caused by the release of some of the solvent
This has no yield value!
How does steric stabilisation of suspensions occur?
Stabilised by repulsive forces due to absorption of macromolecules or surfactants to their surfaces
What is the benefit of topical NSAIDs? When compared to oral NSAIDs.
There is a much lower systemic concentration, and so the common GI side effects do not occur
Define Thixotrophy
An isothermal and comparitively slow recovery, on standing of a material, of a consistancy lost through shearing
So only occurs for sheer-thining systems
The down curve is down and to the left of the original up curve
The extent of thixotrophy is defined by the the area between these 2 lines (known as the area of hysteresis)
What are generally the most stable emulsions?
Those with a mixture of surfactants and a mixture of HLB values
What are the effects of electrolyte concentration on the stability of suspensions?
Low conc –> No secondary minimum is formed, which is needed for pharmaceutical suspensions. But a large primary maximum
Medium conc –> A secondary minimum is formed, and a suitable primary maximum is also shown (preventing coagulation at the primary minimum)
High conc –> No primary maximum or secondary minimum
What does the ‘ideal’ vehicle for a drug, to permeate the skin ,have?
Has no pharmacological effect
Solubilizes the drug
Will release the drug with appropriate kinetics
Chemically/Physically stable
Cosmetically appealing
Non-allergenic/irritating
What are the 4 common types of viscometer?
And what materials can be used in them?
Capillary –> Newtonian only
Falling Sphere –> Newtonian only
Cup-and-Bob –> Newtonian and non-newtonian
Cone and Plate –> Newtonian and non-newtonian
Describe microemulsions
Homogenous, transparent, low viscosity collodial solutions that are very thermodynamically stable (so will form spontaneously)
Eg, small droplets (5-140nm) of one liquid dispersed in another
Several surfactants are always used
What is the main pathway for drugs through the stratum corneum?
Intercellular?
What are the 3 main effects that will cause a change in suspension sedimentation rate?
Increased particle size –> Increase
Increased particle density –> Increase
Increased viscosity –> Decrease
Explain the theory of colloid stability
Attractive forces are inversely proportional to the distance apart (so closer = more attraction)
Repulsive forces increase exponentially with distance apart (so closer = less repulsion)
What is dilatant flow?
The opposite of a pseudoplastic system…. so as sheering stress is increased, it becomes more viscous
When the stress is removed it will return to its original state
This works by the particles spreading out when under pressure, and their being insufficient vehicle to fill the voids
If the colloid particles are negatively charged, why would aluminium ions be useful to form a flocculated system?
As they are positively charged
So they attract the colloid particles via weak interactions, holding them together losely at the secondary minimum
This prevents caking
What are corneodesmosomes?
Major structures in the skin that hold together corneocytes
These need to be degraded for skin to be broken down
What will increase/decrease the max flux of a drug across the stratum corneum?
Increase –> An increase in Log P
Decrease –> An increase in Molecular Weight
What type of ionization of drugs are best absorbed by the skin?
Unionized
Explain the relationship between TransEpidermal Water Loss (TEWL) and the size of the stratum corneum
The less SC that is present, the more water than escapes down its concentration gradient
Is a cream containing 0.1% of clobetasone bioequivilant with 0.1% of a clobetasone ointment?
No
As they produce different pharmacological effects
Explain how percutaneous absorption occurs
The drug is placed on the skin and moves through the SC via intercellular transport. It is then uptaken into the blood via passive diffusion
It then diffuses to where it’s needed in the body, before partitioning and then diffusing into the capillaries.
It is important that the drug is lipophillic to move through the SC, but not too lipophillic that it cannot move around the body
Explain the effect of Propylene Glycol (a co-solvent) on a very lipophillic drug?
By adding PG you increase the drugs solubility in water (up to a degree…as too much and itll like the PG too much to leave!!)
Without any the drug will like the lipophillic nature of the SC too much, and so not partition into the aqueous phase (blood)
What does a high HLB value mean?
The surfactant is hydrophillic
Low HLB = lipophillic
What is meant by the ‘Metamorphosis of a formulation’?
When a topical formulation undergoes a considerable change once applied to the skin
The matrix of the formulation could be changed due to the rubbing (involved in application) or due to loss of volatile excipients (often solvents) –> Causing an increase in viscosity
These changes can increase or decrease the drug solubility in the residual phase
What is caking?
And how can it be prevented?
When secondary energy barriers are overcome, and the particles are forced together at the primary minimum
This is irreversible
This can be avoided by adding a flocculating agent
What does ‘Lag Time’ mean in reference to drugs crossing the SC?
The time taken before a drug reaches the steady state, where the flux is constant
Explain what a Newtonian System is?
Where stress is directionally proportional to the rate of sheer
So if the top of a pile is pushed, it will move with a velocity that is directionally proportional to its distance from the bottom
What is plastic flow?
When van der Waals forces need to be broken to before flow can occur. This creates a yield value (of sheering/stress) that needs to be reached before flow will occur. The higher the yield value = the greater the particle flocculation
The line does not pass through the origin
A non-newtonian system, but acts like one once the yield value has been reached
What is the main benefit of W/O emulsions?
They blend easily with SC lipids…..so will increase the BA of lipophillic drugs
Also has a moisturising and cooling effect
What’s the difference between a Hydrogel and an Emugel?
Hydrogel –> Semi-solid system comprising mainly or large molecules that are inter-penetrated by water
Emugel –> A 2 phase system consisting of large molecules that are interpenetrated by water and a small fraction of emulsified lipids
How would you assess the skin bioavaliability of a drug in vivo on a man?
Define Rheology
The study of the flow or liquids, and the deformation of solids
How would you make a w/o/w emulsion?
Emulsify an o/w emulsion with hydrophillic surfactants
