Mixing lecture 19 Flashcards
Define positive mixture:
components mix spontaneously and irreversibly by diffusion, like 2 miscible liquids. energy can be put in to speed the process up
Define negative mixture:
components tend to separate so constant energy is required to get the 2 substances to mix, reversible so may sediment
Define neutral mixture:
the substances have no tendency to mix or separate spontaneously. energy is required to separate it
Define random mixture:
a PERFECT mix, where any/all of the particles will have the same conc of API and excipients
Define ordered mixture:
components are not independent of each other, where the substances cohesively snd adhesively bind
CAN be better than a random mix
What is the importance of mixing?
- to ensure distribution of API and excipients
- to ensure quality (tested by scale of scrutiny)
- for dosage and safety
- guarantee drug release with the desired rate
Define scale of scrutiny:
the quantity required to test the quality of a mixture (usually one dose e.g. a single tablet)
How does particle size cause segregation?
the smaller the particle, the more it segregates as it falls through the voids between larger particles
How does particle density cause segregation?
the higher the density, the more it segregates (gravity). small and dense particle are most likely to segregate
How does particle shape cause segregation?
the rounder, the more segregation occurs as they mix very well but also ‘unmix’ very well.
non spherical have greater SA:V ratio so increased cohesive effects
How can ordered mixing lead to segregation? although rare
- difference sized coarse particles
- an added external stress
- active sites of coarse particles surface compete with other materials than the fine particles
- coarse particles are not sufficient enough to interact with the finer ones
What are the 3 mechanisms of mixing powders?
- convection = quick, transfer of large particles through the powder bed
- shear = flows of one layer of material over another layer resulting in moving layers at diff speeds. this is preferred with particles who have a tendency to aggregate
- diffusion = movement of individual particles to achieve a true random mix
ALL HAPPEN IN ONE MIXING PROCESS
What 3 things should you consider when mixing solids?
- sequential adding of components slowly
- volume of powder should be adequate for the mixer used
- analyse the mixture after the mixing to identify probs such as segregation
Describe a tumbling mixer for mixing of solids:
- can have an intermediate container
- rotate about an axis with controlled speed
- powder weight ranges from 50g to 100kg
- powder mixture should occupy 1/2 to 2/3 of the mixer volume
- used in the blending of excipients prior to tableting
What kind of mixing occurs when a tumbling mixer is used?
- with a correct speed set, shear mixing occurs
- with movement, powder dilates allowing particles to move so, diffusive mixing occurs
how does an increase in viscosity affecting the mixing process of liquids and suspensions?
the higher the viscosity, the more difficult it is to mix and the longer it takes
however, particle sedimentation rate is reduced so the suspension is more homogenous
What are the 3 methods for mixing liquids?
- bulk transport = quick
- turbulent = constant change in speed and direction
- molecular diffusion = across a conc gradient
What is a propeller mixer used to mix? and how does it work
liquids and suspensions
- angle blades to promote fluid movement in axial and radial direction
How are semi solids mixed?
by planetary mixers
- only shear mixing occurs (not diffusion)
- high risk of ‘dead spot’ with non-mixed materials
How can you minimise segregation?
- similar size of drug and excipients
- use size smaller than 30um (although this can lead to aggregation)
- control the shape
- select components with similar densities
- granulate the mixture
- reduce mechanical stresses
- use of ordered mixtures
