Pharmaceutical Powders Flashcards
Type of pharmaceutical powders:
-Dusting powder
-Oral powder in sachets
- Powders for reconstitution
- inhalation or insufflation products
- bulk powders for tablets and capsules manufacture
Crystalline
Sucrose molecules align and form large “lattices” of molecules, regular repeating structure
Molecules packed in a defined (long range) order
Cool slowly to below melting point
Melt ↔ freeze
Polymorphs, solvates or hydrates, co-crystals
amorphous
molecules of a different size and shape (glucose and fructose) get in the way of the sucrose molecules and stop crystals forming
Molecules packed in a random (short range) order
Rapid solidification/precipitation
Glassy ↔ rubbery (transition)
Moisture sensitive, dissolves faster
Polymorphism
Different molecular packing arrangements (of the same chemical substance) in the crystal lattice
How to determine if a drug is crystalline or amorphous?
X-ray diffraction
X-ray reading - cyrstalline
Very defined shape, high intensity and narrow peaks
X-ray reading - amorphous
low intensity and broad peaks
What is the stages to amorphous > crystalline?
Amorphous > metastable polymorph > stable polymorph > highly crystalline
hydrate
If water is present in the crystal lattice
Due to small molecular size of water and multidirectional hydrogen bonding capability of water
Anhydrous = no water
solvate
If solvents are present in the crystal lattice
Ethanol > ethanolate
DMSO (dimethyl sulfoxide)> DMSO solvate
Give a drug example of a hydrate?
Lisinopril
10mg, 89mg of lisinopril dihydrate
Salt formation ________ the solubility and dissolution rates of acidic and basic drugs
increases
Salt form structure
lattice of positive ions with deprotonated acid negative ions
Give a drug example of a salt form:
Amlodipine - besilate
10mg of amlodipine
What are Co-crystals?
Two or more molecules within the same crystal lattice
In a definite stoichiometric ratio
Not based on ionic bonds
Give two examples of co-crystals?
1) Sildenafil
2) Aspirin - has antiplatelet activity to combat heart attacks and strokes
What are primary features of powder?
- particle size = uniformity, flow, mixing
- surface area = dissolution rate
- shape = uniformity, flow, mixing
secondary features of powder?
- Density = size of tablets and capsules
- Porosity = compressibility, permeability/ water uptake of tablets
- flowability = content uniformity
- compressibility = essential to manufacture of tablets
Equivalent diameters
d”
dp
Projected perimeter diameter
da
Projected area diameter
df
Feret’s diameter
dM
Martin’s diameter
ds
Sieve diameter
dv
Diameter of equivalent volume sphere
dsa
Diameter of equivalent surface area sphere
dmass
Diameter of equivalent mass sphere
dst
Stokes’ diameter
Diameter of a sphere with the same density and settling velocity as the particle
dae
Aerodynamic diameter
Diameter of a sphere with the same terminal velocity in air or some other relevant fluid as the particle
dhyd
Hydrodynamic diameter
Diameter of a sphere that diffuses at the same rate in a liquid as the particle
What equivalent diameters would be used for paint pigment particles?
Projected area diameter
Which equivalent diameter should I choose for aerosol deposition in the lungs?
Aerodynamic diameter
Which equivalent diameter should I choose for sedimentation properties of the material?
Stokes’ diameter
Particle shape - specify:
Solid irregular particles
Porous irregular particles
List the Particle shape terminology
Acicular
Rod-shaped
Flacky
Dendritic
Porous
Angular/irregular
Spherical
Rounded
Good flowability means
easy mixing = rounded or spherical
if the particle shape is acicular/ rod-shaped what does this mean for mechanical strength
increased - tendency to interlock
angular/irregular
What type of particle size if Cohesive effects due to greater surface area
flaky
How to calculate: Surface area (unit2)?
Surface area = 2(length × width) + 2(width × height) + 2(length × height)
Specific surface area per weight unit (Sw)
Weight-specific surface area= [surface area/weight]
Sv = Volume-specific surface area
[surface area/volume]
A ___ particle may be best described as matter of a small size with an immensely ____ surface-to-volume ratio
small
high
Noyes-Whitney Equation
A greater surface area leads to an increase in dissolution rate and improved bioavailability
dC/dt = DA (Cs-C) / h
Surface area measurement , what theory?
Brunauer–Emmett–Teller (BET) theory
Stephen Brunauer, Paul Hugh Emmett, and Edward Teller
