powders- lec 1 Flashcards
1
Q
what is the importance of particle size
A
- The size of drug particles influence their biological activity- particle size influences drug dissolution
- The size of powder particles influences the manufacture of medicines- powder flow, packing to tablets and capsules
- Therefore particle size is the most important solid-state property routinely measured
2
Q
factors affected by particle size
A
- Drug dissolution rate and bioavailability- smaller the particle the greater the SA, the better the dissolution hence better bioavalibility
- Content uniformity
- Taste & texture- smaller particles more taste, larger SA= more dissolved in saliva: large particles= gritty
- Colour- Particles that arent uniform size cant get patchy when put with added colourant (mottling)
- Flow- large particles flow better than smaller: Poor flowability can lead to content uniformity/dose uniformity
- Compressibility- smaller particles, more SA
- Stability-
3
Q
Reasons to reduce particle size
A
- To increase drug surface area and therefore facilitate dissolution
-The products may require it: aerosol products (mean size 3 microns
+To improve suspension stability
-To produce a more homogenous mix: very important with low-dose products-dose uniformity
-To improve powder flow solid dosage form production
4
Q
Particle size drug absorption
A
-The oral absorption profile of many drugs are dependent on particle size: griseofulvin; nitrofurantoin; Spironolactone; several steroids
5
Q
How do we achieve size reduction
A
- milling: cutter mill; hammer mill; ball mill; air jet mill
- reprecipitation
- spray drying
6
Q
The cutter mill
A
- Feeder- where material is added
- consists of a series of knives attached to a horizontal rotor (rotating knives)
- these act against a set of stationary knives
- during milling, the particles fracture between the two sets of knives
- one small enough particles for through a screen ( the screen effects the size of the particles that can be filtered through so size of material)
- SEE blackboard for picture
7
Q
Advantages of cutting mill
A
- the high shear rates are useful in reducing the size of:
- of dried granulation before tabletting
- fibrous crude drugs- roots, before drug extraction
8
Q
The air jet mill
A
- Basically, the system provides a fast stream of particles which are rubbed against each other in a turbulent fluid (air) stream
- The size reduction is related to the pressure of fluid- Increase grinding pressure= decreased particle size
9
Q
advantages of air jet milling
A
- Well established technique
- Accepted by regulatory bodies
- Ease to achieve micronisation with many drug substances (Inhalation)
- Repeat passes may be used to closely control particle size
10
Q
disadvantages of air jet milling
A
- Some particles may not micronise by this technique: particle is too elastic; force imposed by being inefficient to fracture particle
- May promote phase changes in the product
- Possibility of contamination: mill materials; impurities of the air
- The material may have poor flow properties after processing
11
Q
Bead or ball milling
A
- The most common and versatile grinding unit
- A suspension of drug particles is passed through a chamber containing balls or beads of harder material
- The balls are rotated using a paddle
- Rotation speed is very important- at low speeds= incomplete size reduction; if at too high speed= all the beads settle around the circumFrance; correct speed= max time of bead drug contact
- Total number of beads: more beads= more size reduction as the beads are in contact with material more
- Fill the chamber with balls of different sizes and different types (ceramic or steel)
- Screen size= product size
- See BB for picture
12
Q
Factors influencing size reduction- ball milling
A
- Suspension feed rate: decreased feed rate = increase size reduction
- The paddle or rotation speed: increased speed = increased size reduction
- The size and loading of the beads: decreased bead loading= decrease in size reduction
- The suspension concentration: increased conc= decreased size reduction
- The number of passes through the mill: increased number of passes= increase in size reduction
13
Q
Advantages of ball milling
A
- Low initial cost, economical operational and maintenance cost
- Can be used for wet or dry milling
- Can achieve good particle size control
- In an aq. suspension may be possible to prevent temperature changes and limit polymorphic changes
- Can use very hard beads to mill difficult materials
14
Q
Disadvantages of ball milling
A
- Possibility of particulate contamination by milling materials (e.g. stainless stell= very sturdy) but ceramic beads can chip and cause contamination
- Not well-known system for regulatory authorities
15
Q
Hammer mill
A
- The powder/particles are fed into the mil via a hopper
- Rotating hammers impact the powder
- When the product is an appropriate size it passes through a screen
- Size is effected by the length of the hammers in relation to the drum and mesh size of the screen
