Lecture 10 - Particle Science II Flashcards
What is the aim of mixing?
to obtain a homogenous distribution of two or more components (without physical or chemical changes occuring)
When is mixing particularly important?
when very active drugs are employed (<1%), this is to ensure uniformity of active ingredients
and when you have a small therapeutic index
What are positive mixtures?
Materials that mix spontaneously and irreversibly
Examples of positive mixtures?
gases and liquids
What are negative mixtures?
the components tend to separate
Examples of negative mixtures?
Suspensions (solid in a continuous phase)
What are neutral mixtures?
Components neither tend to separate nor mix
Examples of neutral mixtures?
powders = we need energy to achieve mixing
What does having more particles present do?
the more particles present in a dose, the more likely it is that the content will mirror the ratio in the mixture
What does a low proportion of a component in a mixture mean?
the lower the proportion of a component, the more difficult it is to achieve the same (correct) amount in each sample
What are other factors that affect mixing?
particle size, shape
density
flowability
ratio between different components
mixing time
electrostatic interactions
total volume of powders being mixed
friability of the material
humidity
What is segregation?
the opposite of mixing
What is segregation due to?
the fact that powders have different densities, shapes and sizes
How can we check mixing with time?
Take samples from different regions within the mixture and calculate the relative ratio of the components
we then calculate the standard deviation of the samples and plot it against time
What are tumbling mixers?
good for working with granules and free flowing powders
when used at the correct speed there is turbulence and dilation of the powder bed, and mixing by sheering
What is a mixer granulator?
a combination system which mixes granules, the base plate spins ar a high speed, forcing the material up the wall, which then collapses
provides dilation of the powder bed and the speed creates sheering forces within the system
What else is in a mixer granulator?
a blade on the side to break up masses formed
What are agitator mixers?
they have a motion blade and there is mixing of components due to convection
What is granulation?
the process in which homogenous mixtures of primary powder particles form larger, still homogenous particles called granules
What does granulation improve?
powder flow, compaction and prevents segregation
How does granulation prevent segregation?
the larger particles have a uniform consistency so smaller particles will not fall to the bottom
How does granulation improve compaction?
when we make a tablet, granules flow well in the system and flow well into the dye we use to compact them
What other reasons are there to use granulation?
It reduces the generation of dust (important for toxic compounds)
whilst hygroscopic powders form cakes, granules retain their flowability even after absorbing moisture
granules occupy less volume
What is coalescence?
particles coming together to form larger ones
What are the steps of granulation?
coalescence
breakage
abrasion transfer
layering
What happens in wet granulation?
the powders are mixed with a granulating fluid and the mass is forced through a sieve
we then dry and sieve again then lubricate and compress to form a tablet
What is the wet granulation mechanism?
adhesion and cohesion forces in immobile films
interfacial forces in mobile films
solid bridges formed
attractive forces between particles
What do adhesion and cohesion forces mean?
interparticulate distance decreases
increase in the contact area
What are solid bridges?
hardening binders or crystallisation of dissolved substances
What is a high speed mixer/granulator?
components are added and there is an impellor, which spins at a high speed so powder goes up the side and tumbles down
the powder bed is expanded and mixed
once the powder is mixed you add liquid to form granules
chopper bladder to chop up masses
Benefit of high speed mixer?
mixing, massing and granulation all in one kit
What is a fluidised bed granulator?
it has an inlet of air and a nozzle which is the granulating liquid
powder inside are mixed and granulated at the same time
exhaust filters and air goes out of the system
need to optimise this kit to make granules
What is the process of dry granulation?
a pressure is applied to the mixed drug and excipients
partially melted components and fuse then - the intermediate product is broken
sieving, lubrication and compression
Dry granulation mechanisms?
attractive forces between solid particles
solid bridges (by partial melting)
mechanisms of granule formation
Advantage of dry granulation?
not using liquid so there is no need to dry
less steps than wet granulation
