Preformulation - Mixing Flashcards
What is homogenous?
Each component particle lies as nearly as possible in contact with a unit of each other component
What are the different types of mixtures?
Positive
Negative
Neutral
What is a positive mixture?
Mixes spontaneously, energy input not required to separate components
What is positive mixture for?
Miscible fluids
eg. ethanol, H2O + gases
What is a negative mixture?
Segregates spontaneously, energy input required to mix + keep mixed
What is a negative mixture for?
Immiscible phases
eg. oil, H2O + suspensions
What is a neutral mixture?
Components neither mix nor segregate spontaneously, energy input required to mix or segregate components
What is a neutral mixture for?
Powders + pastes
What happens to a neutral mixture once it has been mixed?
It remains stable
What are the mechanisms for liquids?
Bulk transport
Turbulent mixing
Molecular diffusion
Describe bulk transport
Redistribution of large amount of liquid
Large degree of mixing in short period of time
Describe turbulent mixing
Groups of molecules move with constant velocity changes
Describe molecular diffusion
Movement of molecules down concentration gradient
What are the mechanisms for solids?
Connective mixing
Shear mixing
Diffusive mixing
Describe connective mixing
Redistribution of large groups of particles
Large degree of mixing in short period of time
Describe shear mixing
Velocity differences between layers of particles = layers slide over one another
Mixing at interface between layers
Describe diffusive mixing
Powder bed dilation, air introduced into powder bed during mixing
Particles move into air spaces under gravity or mechanical force
What is needed for mixing powders?
Good powder flowability
Why is free-flowing powder easy to mix?
Monosize + low-energy
What can free-flowing powder by susceptible to?
Segregation if different size or density
What may be needed when mixing cohesive powder?
High-energy de-agglomeration
What is the equation used to determine if mixing is adequate?
σR = √ p(1-p)
————
n
σR = theoretical standard deviation of random mixture
p(1-p) = proportion of drug/tracer in mixture
n = total no. of particles in mixture
What happens the longer you mix a mixture?
More homogenous it becomes
What is the mixing index?
σR
What are powders?
NOT perfect mixtures
= settle for random mixtures
What is the scale of scrutiny?
Amount of powder per sample for assessing extent of mixing
Amount = 1 dosage unit
What is an ordered mixture?
Micronized particle adsorbed on surface layer of larger carrier particles
Adsorbed + carrier particles move inter-dependently
What is useful about ordered mixture?
Minimal segregation
What is an ordered mixture useful for?
Potent drugs
What are pharmaceutical powder mixtures likely to be?
Partly ordered
When is segregation likely?
Particle size non-uniform
Particle density non-uniform
Spherical shape (free-flowing)
What are the mechanisms for segregation?
Percolation separation
Trajectory
Elutriation segregation
What is percolation separation?
Small particles fall through voids
What is trajectory?
Larger particles go further as they have more mass based inertia
What us elutriation segregation?
“Dusting out” fine particles on top after motion has increased
How can you minimise segregation?
Uniformed particle size Ordered mixture Select excipients of similar densities Reduce vibration Single-station operation - eg. multiple processes in same equipment
Why is mixing important?
Dosage uniformity: efficacious + safe
Reproducibility during manufacture
Variability inevitable
Active content commonly +/- 5% of label claim
What variability is inevitable?
Error tolerance depends on product + application
High uniformity required for very potent drugs
