Week 2 - Mixing, Milling and Screening Flashcards
List the different types of pharmaceutical mixtures
- Positive mix - spontaneous mix of 2 miscible liquids
- Negative mix - not stabilised mix of immiscible liquids
- requires a lot of energy
- if left over time segregation will occur - Neutral mix - occurs with powders / solids
- mixing only happens if we put in energy,
- no energy = no mixing = segregation occurs
- stable
Explain the mixing process and the 3 types of mixes
- Add excipients and API together
- Put in energy and mix
- longer mix = better mixture becomes - Can form 3 types of mixes
- Perfect mix (NEVER achieved with solids)
- Random mix (overall equal chance of excipient + drug ~ in solids)
- Segregation (worst some parts will only have API + other only excipient)
Why is mixing important
To ensure drug is evenly distributed
Explain the Mixing Mechanisms (solid)
- Convection
- large parts powder are dislocated (moved elsewhere) - Shear
- layers slide over each other = dislocation
- use high sheer mixtures (energy is put into powder bed) - Diffusion
- single particles fall into gaps between other particles
All may occur when mixing solids
Explain the mixing mechanisms (liquids)
- Bulk Transporter
- replaces large parts of solution elsewhere - Turbulent Mixing
- most beneficial + mixes smaller parts of liquid together
3, Molecular Diffusion
- single molecules diffuse
Why is sampling important
Why is scale of scrutiny important
Used to determine how mixed a sample is
- i.e. how many particles of drug is there to particles of excipients
- more particles sampled = better scale + lower SD
SD (standard deviation) - describes the distribution
CV (coefficient of variation) <1% = good
- higher CV = variation of mix is large
What is the impact of segregation (demixing) during and after mixing process
- SD (distribution of particles) goes up and down
- Depends on particle size, shape and density
- large particles (dense) falling due to gravity
- small particles (dust) fall through large particles
- light particles (in gas phase) released generating dust
During:
- have an optimum mixing time (after this time = overmixing = segregation)
Avoiding Segregation
- add excipients
- ↓ particle size
- ↓ low level vibrations
- use hoppers so powder flows quickly
- use ordered mix (small particles adhere to large = dusting prevented)
What is the importance of solid particles and liquid droplets in the manufacturing processes
- particle surface defines how quickly it will dissolve (Noise Whitney)
- particle size can tell us how quickly particle will sediment (Stokes)
List particle size reduction methods (milling)
- Cutter Mill
- rotating knives
- used for fibrous material - Roller Mill
- large particles are crushed between rollers
- used for brittle material
- commonly used - Ball / Vibrational Mill
- Ball: drum is filled with metal / grass balls which rotate over Rach other crushing particles between them
- Vibrational: balls are vibrated (from bottom) + move / crush particles - Hammer Mill
- hammer rotates + gives particles energy to collide with wall = large particles break up
- used for coarse / rough material - Fluid energy / Jet Mill
- jet is put in tube + generates particle flow on outside, centrifugal force causes particles to collide with sides of tube = fine powder
- ONLY way to get microparticles
List 2 separation methods
- Sifting (using sieve)
- particles pass through sieve depending on size
- have different mesh sizes (largest at top)
- small particles will fall through to bottom + large particles remain near top - Centrifugal Screening
- spin particles in circular motion
- particles experience centrifugal force differently depending on mass
- larger particles are moved further
