W4 Pharmaceutical Powders (ZM) 17.10 Flashcards
What are some examples of pharmaceutical powders? (5)
- Dusting powder (antifungals)
- Oral powder in sachets (dioralyte)
- Powders for reconstitution (abx- ciprofloxacin)
- Inhalation or insufflation products
- Bulk powders for tablets and capsules manufacture
What differences are there between amorphous and crystalline?
Crystalline- Sucrose molecules align and form large ‘lattices’ of molecules, with a
regular repeating structure (Regular)
e.g. fudge, rock candy, fondant
Amorphous- Molecules of a different size and shape (glucose and fructose) get in the
way of the sucrose molecules and stop
crystals forming (Irregular)
e.g. lollipops, caramel, candy canes
List some properties of crystalline solids:
- Molecules packed in a defined
(long range) order - Cool slowly to below melting point
- Melt ↔ freeze
- Polymorphs, solvates or hydrates,
co-crystals
List some properties of amorphous solids: (4)
- Molecules packed in a random
(short range) order - Rapid solidification/precipitation
- Glassy ↔ rubbery (transition)
- Moisture sensitive, dissolves faster
What is polymorphism?
- Different molecular packing arrangements (of the same chemical substance) in the crystal lattice
- Differences in molecule orientation or conformation in lattice sites
How can we check if something is crystalline or amorphous?
X-ray diffraction
if Crystalline: X-rays will be scattered only in certain directions (periodic arrangement of atoms)
if Amorphous: X-rays will be scattered in many directions
polymorphism will be inbetween
What is Hygroscopicity?
The tendency of a solid substance to absorb moisture from the surrounding atmosphere
Hydrate Vs Solvate:
What do these terms mean?
- If water is present in the crystal
lattice= Hydrate - Due to small molecular size of
water and multidirectional hydrogen bonding capability of water
Anhydrous = no water - If solvents are present in the crystal lattice = solvate
- Ethanol → ethanolate
- DMSO (dimethyl sulfoxide) → DMSO solvate
What are examples of a medicine that is a hydrate?
Lisinopril dihydrate
Each tablet contains lisinopril dihydrate equivalent to 10 mg anhydrous lisinopri
What are the effects on drug distribution by salt formation? (ionic bond)
Example of a drug in its salt form?
Salt formation increases the solubility and dissolution* rates of acidic and basic drugs
*Dissolution is the process in which a substance forms a solution
Amlodipine besilate
-Each tablet contains amlodipine besilate equivalent to 10 mg 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 (like salts)
Which 2 drugs can you combine to create a co-crystal?
Sildenafil and Aspirin:
Exerts 2 functions
- Sildenafil facilitates improved smooth muscle relaxation and increased blood flow in the human corpus cavernosum
- Aspirin has antiplatelet activity to
combat heart attacks and strokes
Combined= Potential application in the treatment of erectile dysfunction in patients with cardiovascular complication
Can you give examples of the solid states of a bulk drug which determines apparent solubility, and in turn governs the systemic
availability of that drug? (chemical)
Crystalline
Amorphous
Polymorphous
Hydrate or Solvate
Salt form
Co-crystal form
What are the primary features of a powder? (physical) and their relevance? (3)
- Particle size= Content uniformity, flow and mixing
- Surface area= Dissolution rate
- Shape= Content uniformity, flow and mixing
What are the secondary features of a powder? (4)
- Density (spaces between the solids)= Determines size of tablets and capsules
- Porosity= Compressibility, permeability/water uptake of tablets
- Flowability= Content uniformity
- Compressibility= Essential to manufacture of tablets
How is particle size expressed in large objects and small particles?
Large, geometric objects
= Size described in 3D
Small, irregular particles:
= 3D size description impractical, only one dimension (e.g. average diameter) is used
What are some equivalent diameters?
- 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
Equivalent diameters:
What are Stokes, Aerodynamic and Hydrodynamic diameters?
- 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
Which equivalent diameter should I choose for paint pigment particles?
Which equivalent diameter should I choose for aerosol deposition in the lungs?
Which equivalent diameter should I choose for sedimentation properties of the material
- Projected area diameter
- Aerodynamic diameter
- Stokes’s diameter
What are two particle shapes?
Solid irregular particles
Porous irregular particles
*porosity= exposing surface area
What are some particle shape terminologies for 1D, 2D and 3D shapes?
1D= Acicular or Rod-shaped
2D= Dendritic or Flaky
3D= Porous or Angular/irregular or Spherical or Rounded
How does particle shape matter?
- Good flowability = easy mixing
(spherical + rounded) - Tendency to interlock, increased mechanical strength
(Acicular, Rod-shaped, Angular/irregular) - Cohesive effects due to greater surface area (flaky)
Surface area equations:
for a sphere: SA= 4πr^2
for a rectangle:
Surface area =
2(length × width) +
2(width × height) +
2(length × height
Specific surface area per weight unit (Sw)
equation:
Weight-specific surface area
= [surface area/weight]
Specific surface area per volume unit (Sv) equation:
Volume-specific surface area = [surface area/volume]
A small particle may be best described as matter of a small size with an immensely high surface-to-volume ratio
Noyes-Whitney Equation
A greater surface area leads to an increase in dissolution rate and improved
bioavailability
- 𝑑𝐶/𝑑𝑡 = the rate of dissolution of the drug particles
- D = the diffusion coefficient of the drug in solution in the GI fluids
- A = the effective surface area of the drug particles in contact with the GI fluids
- Cs = the saturation solubility of the drug in solution in the diffusion layer
- C = the concentration of the drug in the gastrointestinal fluids
- h = the thickness of the diffusion layer around each drug particle
Surface area measurement (of irregular particles) setup and process:
Brunauer–Emmett–Teller (BET) theory
* Stephen Brunauer, Paul Hugh Emmett, and Edward Teller
- Powder is filled into a vacuum-sealed chamber
- Small amounts of nitrogen gas (or krypton or argon) are added to the chamber
- The nitrogen molecules adsorb to the
the surface of the powder (until the entire
surface (including all accessible pores) is
covered - Pressure transducers sense the amount of gas adsorbed from which the surface
area can be calculated
How does the determination of particle size, shape and surface area help to inform the drug manufacturing process?
