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Pharm 125 > Powders and Granules > Flashcards

Powders and Granules Flashcards

1
Q

What are the particle sizes and dose for microsize and ultramicrosize?

A

Microsize: 4 um (500 mg to 1 g)
Ultramicrosize: 1 um (375 to 750 mg)

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2
Q

What is a powder and granule? How are they used?

A

Powder - a solid or mixture of solids in a finely divided state (less than 1000 um)
Granule - a solid that is the agglomeration of smaller particles (0.2 mm to 4 mm)

  • solid dosage forms
  • intermediate in the production of other dosage forms
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3
Q

What are types of pharmaceutical solids?

A

Crystalline: Regular geometric arrangement or lattice repeated in all three dimensions
Amorphous: Irregular geometric arrangement
Polymeric: Large molecule made up of many small repeating units

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4
Q

What is polymorphism?

A
  • Diff packing pattern of the same molecule, giving different crystal forms
  • Metastable (thermodynamically unstable) converts into one stable form (monotropic polymorphism)
  • If more stable forms exist and reversible transformation = enantiotropic polymorphism
  • Characterization by X ray diffraction, Thermal analysis, spectroscopy
  • Diff physicochemical properties: mp, dissolution rate, bioavailability, stability
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5
Q

Why should we use a metastable form with lower mp?

A

Lower mp = weaker lattice = more soluble = higher DR

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6
Q

What are the types of particle forms?

A
  • Hydrates: Solvent trapped in crystal lattice, less soluble than anhydrous crystals
  • Salts: Two ionized molecules in one crystal lattice (drug + counterion), more soluble, higher DR, greater bioavailability for poorly soluble drugs
  • Co-crystals: crystals with more than 1 component (drug + coformer) or neutral compounds with non-ionic interactions
  • Amorphous solids: not packed in defined order, has a glass transition temp, produced by rapid solidification process or breakage of crystals
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7
Q

What are the particle shapes?

A

Acicular, columnar, flake, plate, lath, equant

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8
Q

What is micromeritics?

A

science and tech of small particles - particle size measurements, size distribution and packing arrangements

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9
Q

What is the importance of particle size?

A
  • Affects flow and packing properties
  • Facilitates drying
  • Improves penetration of particles used in inhalation products
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10
Q

What is the particle size distrubution? What is the mean diameter based on?

A

Cumulative distribution curve: frequency vs particle size

  • Volume, diameter, surface area
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11
Q

What are the types of particle size, their mesh opening size and mesh size number?

A

Coarse, > 355, 20-40
Moderately fine, 180-355, 40-80
Fine, 125-180, 80-120
Very fine, <125, 120-200

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12
Q

What are the methods for determining particle size distribution?

A
  • Microscopy
  • Sieving
  • Laser light scattering
  • Sedimentation
  • Electrical zone sensing
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13
Q

What are the types of microscopy?

A

Optical microscopy: Powder dispersed on slide
Scanning electron microscopy: Powder fixed to aluminium stubs and then coated
Transmission electron microscopy: Powder set on resins, sectioned with microtome, and coated with metal
Dynamic image analyses: automated image analyses light and electron microscopy

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14
Q

What is the sieving method?

A

Pretermined weight of dry powder is passed through wire mesh screens (openings of diff sizes), and the weight of the powder that is retained on each sieve is measured

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15
Q

What are the advantages and disadvantages of the sieving method?

A

Advantages

  • simple, cheap and easy to interpret
  • technology adapted for bulk material

Disadvantages
-the smallest practical sieve size is 38 um
-the amount of energy used to sieve the sample is empirically determined
(over energy can cause attrition of particles and less energy can fail to break the loose agglomerates)

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16
Q

What is light scattering? How is particle size determined?

A

It includes laser diffraction and dynamic light scattering.

PS is detemined by the angle and intensity of scattered light reaching the sensor.

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17
Q

What is the sedimentation method? What are the assumptions?

A

Settling of one particle in a liquid medium under the influence of gravitational and centrifugal forces

Assumes that particles are spherical, particle conc is dilute, and sedimentation is uneffected by the interaction between particles

Stokes law: stoke diameter = root over 18nh/(ps-p0)gt

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18
Q

What is the electrical sensing zone method? (coulter counter)

A

Particle is suspended in a conducting liquid and passed through a small orifice surrounded by electrodes, the change in electrical signal is measured which is proportional to the volume of the particle

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19
Q

What are the three methods of powder production?

A
  • Precipitation and crystallization (can form polymorphs)
  • Spray drying and freeze drying (control over size, shape and composition of particles)
  • Communition (particle size reduction)
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20
Q

What is the mechanism of size reduction?

A
  • Application of external forces to decrease the cohesion between particles
  • Focus energy on cracks (crack propagation)
  • 2% of energy is used to break the materials
  • Other energy is used in elastic/plastic deformation of particles, interparticle friction, particle-wall friction, heat/sound/vibration, and deformation of cracks and metal equipment
21
Q

What are the comminution equipments?

A
  • Coarse crushers
  • Intermediate grinders
  • Fine grinding mills (ball, colloid, pin, air jet/fluid energy, hammer)
22
Q

What are the comminution equipment for small scale?

A
  • Levigation
  • Trituration
  • Pulverization by intervention
23
Q

What are the bulk powder properties?

A
  • Porosity
  • Density
  • Specific Surface area
24
Q

What is true, particle, bulk and tapped density?

A

True density - ratio of mass of the particle to actual volume
Particle density - ratio of the mass of the particle to the volume, excluding gaps and including pores
Bulk density - ratio of the powder bed mass to the volume of loose powder bed (including gaps and pores)
Tapped density - ratio of the powder bed mass to the volume of compacted powder bed (including pores and gaps)

25
Q

What is porosity?

A
  • Volume of the pore interior and gap space in the powder
  • Measured by gas adsorption method or mercury porosimetry
  • it determines the packing efficiency of powder
26
Q

What is specific surface area?

A
  • Determined by particle size and porosity
  • Provides info on void space on particle surface (pores) or within agglomerate
  • Measured by gas adsorption or gas pearmeability procedures
27
Q

Powders with __ bulk density and ___ bulk volume are light

A

low, high

28
Q

What is powder flowability?

A
  • The ease with which a powder flows in specified conditions
  • Refers to both the physical properties that affect powder flow and the equipment required for handling, storage and processing
29
Q

Why is powder flow important?

A
  • Uneven powder flow can result in excess entrapped air in the powder affecting compression
  • Cause lubrication problems and increase dust contamination risks during powder transfer
30
Q

What factors affect powder flow?

A
  • Adhesion/cohesion

- Size, shape, density

31
Q

What is adhesion and cohesion?

A

Adhesion - the tendency of dissimilar particles or surfaces to cling to one another

Cohesion - the tendency of similar particles to cling to one another, intrinsic property of a substance caused by shape and structure of its molecule

32
Q

How does particle size and shape affect flowability?

A

250-2000 um (flow freely)
75-250 um (may flow or cause problems)
<50 um (irregular or no flow)

Spheres flow better than needles

33
Q

How can you measure flowability?

A
  • Bulk density changes (hausner’s ratio, carrs index)
  • Angle of repose
  • Shear cell
  • Flow through an orifice
34
Q

Flowability can be estimated from the ________ of the powder using a tapped density device

A

bulk density

35
Q

What is the angle of repose?

A

The angle between the free surface of the powder body and the horizontal plane when poured from a funnel
- the smaller the angle, the better the flow (less than 35)

36
Q

Flow through an orifice?

A
  • The rate of powder flow is measured as it pours from the funnel
  • The rate is measured by dividing the mass of the powder with time taken
37
Q

What is shear cell?

A
  • more reproducible but time consuming
  • bulk solid sample is loaded into a cell or container, load is applied and the powder bed is sheared until uniform consolidation
38
Q

What is powder mixing? what are the three mechanisms?

A

It is an operation that serves to make two or more components uniformly distributed in a powder bed

Mechanisms:

Diffusion - When powder bed is forced to move/flow, it dilates (increases air space between particles)
Convection - Transfer of large groups of particle from one part of the powder bed to another
Shear - layer of material moves/flows over another layer eg. tumbling mixers

39
Q

What is powder demixing (segregation)? What are the factors affecting powder demixing?

A

The separation of drug from other powder components

Particle size: main cause of segragation

  • > Percolation segragation: when small particles fall between large particles and move to the bottom
  • > Trajectory segragation: when larger particles move greater distance than smaller particles
  • > Elutriation segragation: when mixing, the dust particles move up and then settle on top of coarser particles when done mixing

particle density: denser particles settle at the bottom

particle shape: spherical particles are easier to mix but segregate more

40
Q

How can you minimize segragation?

A
  • select a similar particle size range for API and excipients
  • select excipients similar to density of API
  • control crystallization of API and excipients to give same particle shape
  • granulation of powder mix
  • reduce vibration after mixing
  • production of an ordered mix [micronized powder adsorb onto large carrier particle]
41
Q

What are powder mixing equipments?

A

Mortar and pestle
-small scale, geometric dilution, comminution + mixing

tumbling mixers/blenders

  • v mixers, rotating cubes, cone, etc
  • for good flowing powders or granules

shear and forced circulation mixers

  • blade, ribbon agitator, planetary, high speed, nauta mixers
  • high speed mixers can break up aglommerates, not suitable for materials that fracture easily
  • provides more complete mixing
42
Q

How can you increase powder flow?

A
  • Increase PS
  • Produce ordered mix
  • Use a glidant
  • Make spherical particles
  • Use narrow particle size distribution
43
Q

What are the advantages and disadvantages of powders/granules?

A

Advantages:

  • easy to swallow
  • large amount can be dispensed
  • more chemically stable than liquids
  • faster dissolution and absorption rate
  • can be applied to many body cavities

Disadvantages:

  • harder to mask the tastes
  • cannot be used for potent drugs
  • cannot be used for inactivated drugs or drugs that cause damage to stomach
  • less convenient to carryy
44
Q

What are the types of powder and granule?

A
  • bulk powder
  • divided powder
  • powder and granules for oral solution/suspension and for injection
  • dusting powder
  • inhalation and nasal powder
45
Q

What are bulk powders?

A
  • packed in bulk containers
  • non potent drugs with large doses
  • antacids (sodium bicarbonate), laxatives (psyllium-metamucil), antifungals, (tolnaftate), antiinfectives, douche products
  • few brand products
  • inaccuracy of dosing

Effervescent powders/granules

  • special class of bulk powders
  • API + effervescent salt pairs (citric acid + sodium bicarbonate)
  • helps to cover unpleasant taste or bitter taste
46
Q

What are divided powders?

A
  • bulk powders where individual doses are packaged separately
  • foil and plastic laminates have replaced paper packaging
  • singular 4 mg oral granules for eg
47
Q

What are powders and granules for oral sol/suspension and for injections?

A
  • reconsituted with water/sterile water for injections

- drugs that have physical and chemical stability problems that need to be dispensed in dry states such as antibiotics

48
Q

What are dusting powders?

A
  • designed for external use such as therapeutics, lubricants or protective
  • dispensed in relatively fine state to increase efficiency and decrease irritation
  • has to pass through 100-200 mesh sieve and have good flowability
  • packed in with a perforated lid to allow the powders to be dusted to the effective area
49
Q

What are inhalation powders and nasal powders?

A
  • Insufflations are fine powders of drugs dosed into your nose, throat and ear by the use of an insufflator
  • poor patient compliance and non-uniform doses
  • dry powder inhalers have replaced them

Pharm 125 (4 decks)

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