Powders- Lec 3+4 Flashcards
Powder flow
- Some powders used directly as a dosage form
- Majority of powders are used in the production of other solid dosage forms: tablets; capsules
- Flowability of a powder is crucial when producing these products: along with mixing and compression
Importance of powder flow
- Uniform flow from hopper into tabletting or capsule filling machinery: ensures uniform packing of powder
- Reproducible filling of tablet die: ensures uniform weight and physical-mechanical properties
- Uneven flow may result in entrapped air: will adversely affect tablet quality
Particle properties
- Adhesion and cohesion- surface active forces
- Particle properties and bulk flow
- Particle geometry
Adhesion and cohesion
- Molecular forces cause solid particles to stick to themselves and to other surfaces
- Cohesion: particles stick to each other (similar particles); cohesive forces increase as particle size decrease
- Adhesion: particles stick to other surfaces (2 different surfaces) (e.g. machinery)
Measuring adhesive/cohesive forces
- Powder flow behaviour can be used to characterise adhesive and cohesive forces
- Shear strength: stress necessary to shear a powder bed- How easy to move the plane at the top to the plane at the bottom (If the shear stress is high= existence of more cohesive forces)
- Tensile strength: stress necessary to split a powder bed- wheather the powder bed cracks (if high= high adhesive forces)
- Angle of repose: measurement of the side of a powder heap (bigger the angle = more cohesive)
particle properties and bulk flow (What are powder flow promoted and prevented by)
- Equilibrium exists between forces that promote powder flow and those that prevent it
- Flow promoted by: gravitational force, particle mass, angle of powder bed
- Flow prevented by: cohesion, adhesion, mechanical interlocking (peak and trough interlock)
Particle properties and bulk flow: effect of particle size
-Effects of particle size:-Cohesion and adhesion occur at the particle surface
-Decreasing particle size increases surface area
-Finer particles are more cohesive than coarse particles
-Size >250 micron- usually free flowing
-Size <100 micron- Cohesive powders, poor flow quality
<50 microns- very cohesive
-Size <10 microns- Extremely cohesive powders; important for inhalation powder
Particle properties and bulk flow: effects of particle shape
- Different shapes have different interparticulate contact areas
- Spherical particles have a minimum contact
- Particle flakes have high surface to volume ratio and poorer flow qualities
particle properties and bulk flow: effect of particle density
- Powder flow under the influence of gravity
- More dense particles are less cohesive than less dense particles and flow better
Packing geometry
How they pack
- Pouring a powder into a container produces a powder bed: particles will pack according to their shape; air will be entrained, causing pores
- Silent vibration of the powder bed will mobilise the particles: may result in closer packaging
- Greater number of contact points once air pours have been removed leading to increased compressability
- Trapped air in a tablet is called laminating and capping- sheets of tablets come off due to trapped air
Characterisation of powder flow (methods of measurements)
- Indirect methods: angle of repose(easy to set up, multiple variables) ; shear cell stress; bulk density
- Direct methods: hopper flow rate; recording flowmeter
Angle of repose measurements
- Can be used as an indirect measure of powder flow: related to INTERPARTICULATE COHESION
- Several different methods available: fixed height cone, fixed base cone, tilting table measure angle of repose; rotating cylinder measures dynamic AoR; ledge, crater and platform measure drained AoR
- The more cohesion= large angle of repose
- Very cohesive materials tend to stack on top of eachother = large angle
Shear cell measurements
- Can obtain a ‘Flow Factor’ from shear cell apparatus
- > 10 -free flowing
- > 4-10 - easy flowing
- > 1.6-4. - cohesive
- <1.6 - very cohesive
- How difficult it is to move the top plane of the powder bed compared to the bottom plane
Bulk density measurements
- Bulk density of a powder is dependant on particle packing: changes as the powder consolidates; a consolidated powder is more resistant to flow
- Ease of powder consolidation is used as an indirect measure of powder flow: compare bulk density to tapped density; free-flowing powders will demonstrate little consolidation
Hausner ratio
- Hausner ratio= Tapped density/Bulk density
- Powders with low interparticulate cohesion have a low Hausner ratio of 1.2
- More cohesive, less free-flowing powders, have a Hausner ratio >1.6
Carrs index
- Carrs index = (tapped density- bulk density/ tapped density) x 100
- 5-12= excellent free flowing granules
-12-17= good free flowing powdered granules
-17-22 = fair powdered granules
-22-28 = poor very fluid powders
-28-35 = poor fluid cohesive powders
35-38 = very poor fluid cohesive powders
->40 extremely poor cohesive powders
Hopper flow rate
- Simplest method of determining powder flow
- Measures rate at which powder flow from hopper
- Modification of angle of repose
recording flowmeter
-Similar to the previous method, but powder falls onto a balance
Improvement of powder flow
- Can be achieved by:
- Altering particle size or size distribution
- Altering particle shape or texture
- Altering particle surface forces
- Incorporating flow additives
- Altering the process conditions
Altering particle size
- Coarse particles are less cohesive than fine particles
- Optimum size exists for free flow
- Do not use a finer powder than is necessary: may depend on the application e.g. powders for inhalation must be very small
- Can also adjust size distribution by sieving: removes fines or increase to coarse
- Smaller particle= greater SA = increased interaction between interaction
Altering particle shape
- Spherical particles have better flow properties than irregular particles
- spherical particles= less contact points= less interparticle forces= better flow
- Powder production technique can generate near-spherical particles: e.g. spray-drying
- Texture may influence flowability: rough particles will be more cohesive than smooth particles
- Rough particles= mechanical interlocking = less flow
Altering surface forces
-Electrostatic charges can build up during powder flow
-Can alter process to limit this: reduce speed of powder flow; reduce length of pipes; use earth connections to discharge forces
-Moisture content may need to be strictly controlled: Especially important for hygroscopic materials
+Uneven surfaces with small of moisture increases flow- this is because the moisture will form a film and fill in depressions in particle shape causing it to become spherical
+Further increase in moisture will decrease flow by causing the particles to clump together
Incorporate additives
- Flow activators also was known as glidants: may also have lubricant or anti-adherent; improve flowability by reducing adhesion and cohesion
- Very small particles so when blended with the granules- the lubricant will deposit itself on the surface of the granule/particle- this then acts as a ball bearing- this minimise contact points of the particles
- Examples include: (electrostatics- talc, Mg stearate) (reduces bulk density- colloidal silicon dioxide) (Mg oxide- disrupts film of absorbed water)
Altering process conditions
- Vibration-assisted hoppers: adds stress which encourages powder flow; amplitude and frequency of vibration can be altered to produce effect
- Force feeders: vibrating baffles, fitted at base of the hopper; slightly sloping moving belt; counter-rotating paddles at base of hopper
Powdered dosage forms
-Powders for oral administration:
+bulk powders-All doses in one pack
+divided powders
-Other routes of administration: dusting powder; insufflation; powder for reconstitution; dry powder inhalers
Oral powders
- Bulk powders: suitable for relatively non-toxic drugs that are required in a large dose: compound Mg trisilicate oral powder
- Divided powders: supplied as individual doses, separately wrapped e.g. lemsip
Advantages of oral powders
- More stable than liquids
- Convenient for drugs which require a large dose
- Faster dissolution rate than tablets/capsules
Disadvantage of oral powders
- Bulky, less convenient to carry
- Taste- making is a problem
- Not suitable for potent/low dose drugs
- Not suitable for orally-sensitive drugs
Dusting Powders
- For external use only
- Contain ingredients intended for therapeutic, prophylactic or lubricant purpose: must be sterile if applied to open wound; must be free from pathogens if used for superficial skin conditions
Insufflations
- Medicated powders are blown into ear, nose or throat using an insufflators
- Rarely used: inelegant preparations; less convenient to apply than other topicals; difficult to deliver the same dose each time
- Currently being revived for systemic delivery following application to the nose
Powders for reconstitution:-Oral antibiotics
- useful for patients who cannot swallow capsules or tablets
- cannot supply as liquid preparations, due to drug instability (hydrolysis)
- Supply as dry powder, to be reconstituted by the pharmacist prior to dispensing
- Dry powder will have a longer shelf-life
- Dispensed product will have a 7-14 day expiry
Powders for reconstitution: powder for injection
- Used for drugs for injection that are unstable in solution
- Reconstituted immediately prior to administration
- May also contain other excipients e.g. tonicity modifier (0.9% NaCl
- WFI
Dry powder inhalers
-Administration of drugs to the lung requires very small particles: 1-5 microns very cohesive
-Several devices available: spinhaler, rotahaler, diskhaler, accuhaler
-Used to deliver drug to treat local conditions: asthma, COPD, cystic fibrosis
-Also for systemic delivery:
Exubera for insulin delivery
Dry inhalers
-Typically comprise micronised drugs blended with a large carrier particle (e.g.):
+Improve flow during manufacture
+improve powder aerosolisation properties
-Powder flow during inhalation is critical: must flow well from device;
+drugs must detach from carrier particle;
+drug must deposit at correct part of the lung
+The drug detaches from the carrier particle w/ drug entering the lungs and the carrier swallowed
Dry powder inhalers (research0
- Several researchers currently investigating spray-drying to generate better inhalable powder
- Incorporate flow additives, in spray drying process
- Generate spherical particles
- Decreased electrostatic forces
- Decreased cohesion
