Mixing and size reduction Flashcards
What is a powder? What does particle reduction do?
Mix of dry particles disperesed in a matrix
- Powder can be free flowing (un-sticky) or cohesive (sticky forming aggeregates)
- Particle reduction increases the chance of cohesiveness
Explain when powder mixing and size reduction occurs and what it achieves
- Occurs during process of drug manufacturing and formulation
- Purposes of powder mixing and size reduction –> ensure optimum quality of final product
- Form a uniform composition so that when a sample is withdrawn from a bulk –> it represents overall composition of bulk
- Obtaining uniformity in final product is crucial for proper dosing
- Different powders can be mixed to form a random mixture, an ordered mixture or an interactive mixture
- Powder mixture may contain particles of same or different size, denisty and shape
What is random mixing?
Probability of selecting a particle of the mix is the same at all locations of the mix and is equal to the proportion of such particles in the mixture
- For example, a 50:50 powder mix should contain two adjacent particles with each half occupying the mix
What is required for random mixing to occur
At rest: particles are in spatial equilibrium
to enable mixing to occur
- The powder has bed to be expanded
- Sufficient shearing force needed to be applied to achieve relative moment of the particles in the powder bed
What are the types of mixing force (random mixing)?
- Pure tension: Separates particles but does not change their relative position
- Pure compression: compresses particles but does not change relative location
- Shear: causes relative particle movement
What is the process of powder mixing?
- Expansion of the powder bed
- Application of adequate shear forces
- Providing sufficient time for proper mixing
- Prevention of segregation (demixing)
What are some forces and factors that control the process of of powder mixing?
Forces
- Electrostatic
- Van der Waals forces
Factors
- Particle size
- Particle density
- Particle shape
What are the components of ordered powder system?
- Surface active force (e.g. Van der Waals) as well as adsorbed films used
- Particle size, density and shape
- Particle adhesion and compatibility
Describe pharmaceutical requirements for random mixing and the equation associated with it
Where samples are taken from a random mix of the same particle size, shape and density:
SD = [p (1-p)/n]½
p = proportion of active ingredient
n = number of particles in the sample
What is a common measure of the degree of mixing?
degree of mixing can be achieved by the following equation:
M = SR/SM
Where:
ØSR = standard deviation of a random mix
ØSM = standard deviation from samples
- As mixing continues, the value of M should approach 1
- More mixing is carried out = smaller the standard deviation becomes
Ordered powder mixing process –> discuss cohesiveness
- Cohesiveness may occur if different powder particles have different size, shape and density
- When powder mix has significant particle-particle interactions, cohesiveness is most likely to occur
- Increased SA = cohesiveness
- Segregation most likely will not occur when fine powders were adsorbed onto host crystals –> results in ordered powder mixtures
How does an ordered mix coarse?
- For an ordered mix to occur as coarse (usually excipient compount) –> it is coated with fine particles adsorbed to the surface
- Ordered mix gives higher degree of homogeneity than random mix
- Ordered powder mix can also be obtained if the active ingredient is dissolved in a solvent which then evaporates (heated) while mixing a coarse excipient
Requirements for formation of a perfect ordered system?
- Very fine mono-sized cohesive drug
- Coarse mono-size diluent (excipient)
- Mono-particular dispersion of the drug
- Saturation of surface sites on diluent by the drug
- Adequate mixing forces to achieve these requirements
- High adhesional stability
- Coarse component breaks up cohesive aggregates of fine powder form
- When sufficient mixing forces operate, mixing occurs rapidly (often less than 10 minutes)
- If higher homogeneity than a random mix –> often indicates some ordered mixing has occurred
- Larger sized components needs to be in large excess and only a limited number of sites are likely to adsorb the active principle.
- Hence only low amounts of drugs can be adsorbed.
What are some problems with the ordered powder mixing process
Segregation
- Occurs when the coarse phase has a variable size distribution
- Weight of drug adsorbed is directly related to the surface area
Mixing forces: must be sufficient to break up aggregates of the fine component but not to rupture the adhesive bond structure
>Saturation of adsorption sites leaving excess powder as small aggregates that segregate
What is preferntial adsorption?
Where an ordered mixture has been achieved and a second fine component is added: It may preferentially adsorb displacing the original particles
- A third component can strip the adsorbed component from the coarse material without itself being adsorbed
- Charging particles may improve the stability of an ordered mix
- Moisture content can also influence the stability of a mixture
What are the types of mixers, their mechanisms, their uses and issues
