Ceutics Lecture 5 HW

Explain three limitations or disadvantages of the following methods to determine particle size

a. Microscopy

b. Volume diameter

a. Allows assessment of particle morphology (1 dimension only) and Slow, tedious, requires statistical analysis

b. Does not discriminate between individual particles and aggregates and Instrument is expensive and requires maintenance and specialized training

Describe three sensing mechanisms used in instruments to determine volume diameter of a sample

Coulter Counter: voltage; detects changes in electrical resistance as particles pass through an aperture

Dynamic Light Scattering: light scattering - Brownian motion

**smaller particles move more and faster than larger

Laser Diffraction: Measures particle size based on how a laser beam diffracts (diffraction pattern) when it impinges on particles or droplets

A sample of the fluticasone propionate powder that you analyzed in the images described in problem #1 (above) and determined the geometric diameter (dg= 50% size) was also analyzed by laser diffraction and the volume diameter (dv) was determined to be 17.25µm. Is this diameter comparable to the one that you obtained in problem #1? (i.e. is dg = dv ?) If yes, explain why...if not, explain why.

Geometric diameter (dg) = 50% size from microscopy; about 1.6ish

Volume diameter (dv) = 17.25 µm from laser diffraction

Geometric diameter (dg) and volume diameter (dv) are not comparable due to the nature of laser diffraction. It cannot tell aggregates or smaller particles stuck together apart from genuinely large particles.

If you assume that the fluticasone proprionate microparticles are spherical and had a density of 0.035 g/cm3, what is their surface area?

Since microparticles are spherical,

S = 6/(pd)

S = 6/(0.035 x 12.75 x 10^-3 (from last flashcard))

= 99378.9 cm^2/g

Describe the principles on which the following determinations are based on:

a. Surface area by gas adsorption

b. Surface area by air permeability method

c. True density of a solid

a. Surface area by gas adsorption:

- Based on the Brunauer Emmett Teller (BET) Equation

- Assumes that a monolayer of gas (usually nitrogen) or gas mixture (nitrogen/helium) is adsorbed on the surfaces of particles when a sample of powder is placed in a container where gas is circulated

b. Surface area by air permeability method:

- Based on the Kozeny Carman Equation

- Surface area proportional to the pressure drop or permeability of a fluid (usually air) flowing through a compacted sample of powder

c. True density of a solid:

- Measurement with a pycnometer based on Archimides' principle: "The weight of the displaced fluid is directly proportional to the volume of the displaced fluid"

- gas penetrates tiny pores and displaced volume gives true density

To gain more insight on the performance of the acetaminophen/Eudragit® powder blend in the tableting machine, the engineer in charge has asked quality control to determine the compressibility index (CCI). The analyst weighs 3 g of the powder blend and places it in a graduate cylinder, determining that the volume the powder is 18 cm3. Then he taps the cylinder 250 times and observes that the volume of the powder is now 12 cm3. Help him to determine the compressibility index of this powder.

CCI = (pt - p')/pt x 100

pt = m/vt = 3/12 = 0.25

p' = m/v' = 3/18 = 0.167

CCI = (0.25-0.167)/0.25 x 100 = 33.2%

Identify three interaction forces that occur in powder samples

- Van der Waals

- Electrostatic interactions

- Mechanical Interlocking

- Capillary Forces: moisture

A 3 year old was diagnosed with an ear infection and the doctor prescribes an amoxicillin suspension. You are asked to fill the prescription and the mother asks you to reconstitute the powder, since she does not have at home something to accurately measure 100 ml of water. After you add the water, you notice that the powder does not suspend and remains on the bottom of the bottle. You try with 3 more bottles with the same result. Hypothesize what can be the reason for this. How would you prove your hypothesis?

No wetting or suspending agents within batch, see if powder floats on water

What method to determine particle size would you use for the following dosage forms and why?

a. Injectable solution

b. Dry powder inhaler

c. Granules for reconstitution

d. Powders to fill capsules

e. Tablet excipients

a. Injectable solution: light scattering

b. Dry powder inhaler: Laser diffraction

c. Granules for reconstitution: laser diffraction

d. Powders to fill capsules: sieving

e. Tablet excipients: sieving

In the practical sense, what is the difference between light scattering and laser diffraction to determine particle size?

Laser diffraction is the go‑to method for pharmaceutical powders, granules, and inhalation products because it handles large particle sizes and gives a volume‑based distribution.

Light scattering (DLS) is used for nanoparticles, emulsions, and colloids where Brownian motion is measurable.