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Hypertension > Powders > Flashcards

Powders Flashcards

1
Q

What is a powder

A

A collection of particles usually 10-100um in diameter

Bulk powder acts as a fluid
Flow isnt completely free

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2
Q

Manufacturing of tablets and capsules will rely on….

A

Flow properties of the drug and excipients

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3
Q

What are flow properties determined by

A

Particle size, shape and particle-particle interactions

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4
Q

A drug must ….

A

dissolve in GIT prior to absorption

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5
Q

Drug dissolution equation

A

Noyes-Whitney

dm/dt = DA(Cs-c) / h

dm/dt is dissolution rate
D is diffusion coefficient
A is the available surface area
cs is the solubility
c is the concentration
h is the diffusion layer thickness

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6
Q

Wh at is a particle

A

Is a single solid entity of a material usually in um size rnage

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7
Q

Nature of powders

A

Crystalline but doesnt mean single crystals

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8
Q

Crystal habit

A

External shape of Crystal - usually refers to single crystals

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9
Q

Monocrystaline systems

A

Have well defined habits - cubic, plates, needles

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10
Q

Polycrystalline systems

A

In practise most systems are poly

Composed of aggregates of micro crystals usually less than 1um

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11
Q

If we looked a a powder particle under a microscope

A

Non-uniform
Porly defines
Crystalline but composed of many tiny crystals bonded together

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12
Q

Complications

A

Individual particles can clump together to form aggregates

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13
Q

What does particle size mean

A

Hard to define
Particles can assume any shape
Each method of size analysis makes assumptions

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14
Q

What does it mean if a particle is monosized or mono disperse

A

Every particle is same size and hence population may be defined by a singular parameter

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15
Q

In practise we need to….

A

define both some sort of average size
and also the distribution around that average

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16
Q

Simplest way of displaying size data

A

Histogram where proportion is plotted against size

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17
Q

Histogram distributions

A

Symmetrical is normal distribution has one peak int he middle
+skewed and - skewed has a peak and tail on either side
Bimodal has 2 peaks

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18
Q

How to put numbers into distribution charts

A

Use the mode

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19
Q

Mode, median and interquartile range

A

Mode = size at which greatest frequency of particles occurs
Median = size at which 50% of particles are larger or smaller
IQ range = rnage between 25% and 75%

20
Q

What is sieve analysis

A
  • Set of sieves with widest mesh at top, finest at the bottom
  • Sieves usually automatically shaken for a predetermined
    period of time (usually around 20 minutes)
  • quick
  • accurate
  • not used often
21
Q

Microscopy to measure size

A
  • Light microscope can measure particles down to about 10 um, scanning electron microscope down to about 100 nm
  • Old fashioned method
  • This is a 2-dimensional technique
  • size and shape
22
Q

Electrical stream sensing one method

A
  • Works on the basis of particles suspended in an electrolyte solution
  • Particles pass through an aperture of known diameter. Electrodes either side of aperture will register increase in resistance as particle displaces its own volume of
    electrolyte
  • measure volume diameter (diameter of sphere with the same volume as particle)
  • used for range of 0.1-1000um
  • quick and easy
  • can cause blockages often
23
Q

Laser light scattering methods

A
  • Use diffraction of light as means of calculating diameter and size range
  • Laser applied to suspension of particles in aqueous or non- aqueous medium
    Two types:
  • large-particle analysers (measure 1-1000 um)
  • photon correlation spectroscopy (for smaller particles, 10 nm – 1 um)
  • rapid and reliable
24
Q

Why is powder flow important

A

• Uniform feed into tableting or capsule filling equipment, leading to uniform weight and mechanical properties
• Ease of handling and transfer of powders

25
Q

Adhesion and cohesion

A
  • Adhesion – attraction between a material and a different material
  • Cohesion – attraction between a material and an identical material
  • Cohesive powders do not flow well
26
Q

What is van der walls and wat is it dependant on

A

Non specific

Dependant on area of contact between particles - finer particles are more cohesive

27
Q

Flow of large, small, needle and round particles

A

Large flow better than small
Round flow better than needles

28
Q

Measurements of powder flow properties

A
  1. Angle of repose
  2. Bulk density measurements
29
Q
  1. Angle o repose
A

Simple method of pouring powder onto a plate

Angle to horizontal measured

Powders will flow until the angle of inclination becomes too malleable to overcome cohesive forces

> 50degrees = poor flow
25degrees = good flow

30
Q
  1. Bulk density measurements
A

Density of powder bed may be used to assess flow

Measure bed flow before and after consolidation by tapping it

Flow ability measured by hausner ratio Df/Do

1.2 = good flow
>1.6 = poor flow

When tap the particles get closer together

31
Q

What is flow through hopper

A

Particle flow through orifice and over time a depression forms in upper surface. Powder falls though the central channel until an empty or dead zone forms. Particles in middle zones flow faster over the outer slower zones

32
Q

What is rat holing and why worry

A

Problematic as there is danger of it collapsing and leading to sudden flooding. It’s where the particles build up on the sides of the hopper with a channel in the middle

Tablet and capsule manufacture are highly dependent on flow form hopper

Poor flow means non-reproducible fill and non reproducible dose

33
Q

Why s powder mix important

A

Need even mix especially when preaparing high potency drugs

Segregated mix is a half and half. Ideal mixing is even I and then random mix

34
Q

What is random mix

A

Probability of finding a type of particle is proportional to total number in mix

35
Q

How to access randomness of mix

A

Take several samples and measure how many purple squares in each

36
Q

3 mechanisms of mix

A

Convective - take a portion of material from a pile, move it to another location

Shear - powder heap will collapse into hole created (shear plane generated)

Diffusion - if powder bed lifted and dropped. Particles then tumble over each other and mix on particulate basis

37
Q

Tumbling mixer

A

Y-cone blender

Shear and diffusive via a tumbling motion

38
Q

Roller mixer

A

Bottle containing material placed on rotating cylinders

Gentle

39
Q

Agitator mixer

A

Rely on motion of a blade or paddle - like kenwood

Connective and shear

Danger of dead zones if paddle doesn’t involve movement in all part of the mix

40
Q

What is large and small particles mix

A

Smaller will absorb onto the surface of large particles

Important for aerosols

41
Q

Optimal mixing time

A

Too long and the system seperate

42
Q

Variation in particle size

A

Size, shape, density

Particle will behave differently

Similar particles tend to congregate

43
Q

percolation segregation

A

Small will fall through voids

44
Q

trajectory segregation

A

Large will have more momentum and move further distances than small

45
Q

Particle shape effects

A

Spherical particles segregate more readily than non-spherical due to shape and SA:volume
Particles may also change shape during processing so tendency to segregate may also change

46
Q

Mixing times

A

For non-segregated mice the longer the mixin Time the better

For segregating mixes, there is an optimum time after which the rate of segregation exceeds the rate of mixin

Hypertension (24 decks)

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