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PH2503- formulations > Powders- Lec 3+4 > Flashcards

Powders- Lec 3+4 Flashcards

1
Q

Powder flow

A
  • 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
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2
Q

Importance of powder flow

A
  • 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
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3
Q

Particle properties

A
  • Adhesion and cohesion- surface active forces
  • Particle properties and bulk flow
  • Particle geometry
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4
Q

Adhesion and cohesion

A
  • 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)
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5
Q

Measuring adhesive/cohesive forces

A
  • 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)
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6
Q

particle properties and bulk flow (What are powder flow promoted and prevented by)

A
  • 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)
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7
Q

Particle properties and bulk flow: effect of particle size

A

-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

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8
Q

Particle properties and bulk flow: effects of particle shape

A
  • 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
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9
Q

particle properties and bulk flow: effect of particle density

A
  • Powder flow under the influence of gravity

- More dense particles are less cohesive than less dense particles and flow better

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10
Q

Packing geometry

A

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
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11
Q

Characterisation of powder flow (methods of measurements)

A
  • Indirect methods: angle of repose(easy to set up, multiple variables) ; shear cell stress; bulk density
  • Direct methods: hopper flow rate; recording flowmeter
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12
Q

Angle of repose measurements

A
  • 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
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13
Q

Shear cell measurements

A
  • 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
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14
Q

Bulk density measurements

A
  • 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
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15
Q

Hausner ratio

A
  • 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
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16
Q

Carrs index

A
  • 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
17
Q

Hopper flow rate

A
  • Simplest method of determining powder flow
  • Measures rate at which powder flow from hopper
  • Modification of angle of repose
18
Q

recording flowmeter

A

-Similar to the previous method, but powder falls onto a balance

19
Q

Improvement of powder flow

A
  • 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
20
Q

Altering particle size

A
  • 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
21
Q

Altering particle shape

A
  • 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
22
Q

Altering surface forces

A

-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

23
Q

Incorporate additives

A
  • 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)
24
Q

Altering process conditions

A
  • 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
25
Q

Powdered dosage forms

A

-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

26
Q

Oral powders

A
  • 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
27
Q

Advantages of oral powders

A
  • More stable than liquids
  • Convenient for drugs which require a large dose
  • Faster dissolution rate than tablets/capsules
28
Q

Disadvantage of oral powders

A
  • Bulky, less convenient to carry
  • Taste- making is a problem
  • Not suitable for potent/low dose drugs
  • Not suitable for orally-sensitive drugs
29
Q

Dusting Powders

A
  • 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
30
Q

Insufflations

A
  • 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
31
Q

Powders for reconstitution:-Oral antibiotics

A
  • 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
32
Q

Powders for reconstitution: powder for injection

A
  • 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
33
Q

Dry powder inhalers

A

-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

34
Q

Dry inhalers

A

-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

35
Q

Dry powder inhalers (research0

A
  • 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

PH2503- formulations (18 decks)

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