Intro to Powder Solids

Question 1

Properties of Mesophase Molecules

Answer 1

1. Organic molecules
2. Elongated or rectilinear molecules
3. Rigid molecules
4. Possess strong dipoles and easily polarisable group, hence directional

Question 2

Two classification of mesophase molecules

Answer 2

1. Thermotropic: Transition by temperature change

2. Lyotropic: Transition with solvents

Question 3

Characteristics of solids

Answer 3

1. Low kinetic energy, hence more stable
2. Rigid structure that can resist deformative forces (due to short intermolecular distances which make them dense and fixed)
3. Organised as crystalline or amorphous solids

Question 4

Benefits of solid dosage form

Answer 4

1. Better chemical stability than liquid
2. Does not promote microbial growth when dry
3. Less bulky
4. Convenient and ease of handling
5. Flexible, single or multiple chemical components can be incorporated into solid dosage form

Question 5

Describe the crystal form of a solid

Answer 5

• Ordered structures
• Particles form 3D repeating patterns, and the basic repeating pattern is the unit cell of the structure (representative structure of the crystal)

Question 6

Define polymorphism in solids. Why does polymorphism occur?

Answer 6

Polymorphism: ability of solid to exist in more than one form of crystal structure (i.e. different crystal packing)

Solids exhibit polymorphism to minimise crystal lattice energy under specific thermodynamic conditions

Question 7

Why is polymorphism a worry in pharmaceutical manufacturing?

Answer 7

Different polymorphs exhibit different physical characteristics, which may affect efficacy of drug (E.g. bioavailability, dissolution)

Question 8

Characteristics of an amorphous solid (compared to crystallien?)

Answer 8

1. Irregular shape with no fixed arrangements
2. Isotropic with no well-resolved X-ray patterns
3. No fixed melting point
4. No fixed heat of fusion
5. Higher susceptibility to chemical degradation
6. More soluble

Question 9

What is “nanocrystalline” in amorphous state, and what is an advantage of having a nanocrystalline amorphous solid

Answer 9

Amorphous solids, but with small units of crystalline form within structure. This helps to increase stability of the amorphous solid.

Question 10

Methods to determine crystallinity and/or polymorphism

Answer 10

1. X-ray diffraction (standard method)
2. Melt behaviour
3. Raman spectroscopy
4. Others: IR, NMR

Question 11

Briefly describe the principle of X-ray Diffraction

Answer 11

When the wavelength of the x-ray is equivalent to the intra-atomic spacing between planes in crystals, the x-ray is reflected and the reflection is captured.

Question 12

Distinguish the x-ray diffractogram between crystalline and amorphous state

Answer 12

• Crystalline: Sharp distinct peaks

- Amorphous: no distinct peaks, or overlapping peaks

Question 13

Name two ways to measure melt behaviour of a solid

Answer 13

1. Hot stage microscopy

2. Differential scanning calorimetry

Question 14

Describe the principle of Differential scanning calorimetry

Answer 14

• Sample heated in a pan and enthalpy change is measured as a function of temperature or time
• The difference in the amount of heat required to increase temperature of a sample and reference is noted

Question 15

Distinguish the heat-flow graphs obtained from DSC of crystalline solid VS amorphous

Answer 15

• Crystalline: usually one peak (melting point)
• Amorphous: multiple peaks (due to glass transition, crystalline re-formation)

Note that when amorphous material melts, it is transforming into a more stable crystalline form, and is not turning into molten state

Question 16

Describe the principles of Raman Spectroscopy in determining polymorphism/amorphous

Answer 16

• When electromagnetic (EM) radiation is scattered, photon of incident radiation is absorbed by an atom which transits to excited energy state.
• The atom does not fall back to its original ground state, hence it emits a photon with energy different from the EM radiation
• This photon can be captured, its energy measured
• Different solids has different vibrational energy states, which can be deduced from spectra obtained, and hence can be used to identify the solid

Question 17

Advantage of Raman spectroscopy

Answer 17

1. Distinct spectroscopic property (fingerprint of a molecule)
2. Fast measurement time
3. Can measure from small spot size to a few microns
4. Non-destructive
5. Can do qualitative analysis when the solid is a mixture (using intensity of peaks)
6. Not affected by presence of moisture or water