Introduction to Solids: Powders

Question 1

Describe the organisation of the constituents in solids.

Answer 1

Crystal form:

• ordered and repeating patterns between atoms, ions and molecules in a crystal lattice.
• basic repeating pattern is the unit form of the structure.

Amorphous form:

• encompasses amorphous and nanocrystalline states
• improves solubility and drug stability (nanocrystalline form)

Question 2

Compare the differences between crystalline and amorphous forms.

Answer 2

Arrangement: orderly for crystalline, irregular with no definite arrangement for amorphous.

Physical property: anisotropic, with sharp x-ray diffraction patterns for crystalline, isotropic, with not well-defined, x-ray diffraction patterns for amorphous.

Melting point: sharp for crystalline, over a range for amorphous

Heat of fusion: definite for crystalline, not definite for amorphous.

Stability: more chemically stable for crystalline, more liable to degradation for amorphous.

Question 3

What are the major characteristics of solids?

Answer 3

• particles are well-organised and immobile, oscillating about their fixed positions
• lowest kinetic energy amongst the three states, chemically stable
• structural rigidity, resist deformative forces
• particles are closely packed together with a definite shape
• molecules have orientation and periodicity
• solid molecules are mechanically strong and incompressible
• characteristic properties: melting point, diffraction

Question 4

Why are most drugs delivered via the solid dosage forms?

Answer 4

• Markedly better chemical stability
• Does not promote microbial growth when dry
• Lower bulk volume
• Ease of handling, added convenience
• Flexible, single or multiple dosage forms

Question 5

What is polymorphism?

Answer 5

• Ability of a solid to exist in more than one form or crystal structure due to the differences in crystal packing.
• Reason for variation in crystal packing is to minimise crystal lattice energy under specific thermodynamic conditions.

Question 6

What are the properties of polymorphs?

Answer 6

• chemically similar, but with different physical properties.
• if a polymorph transforms from one form to another, the original form that it was in is not chemically stable.
• polymorphic crystal forms: tetrahedral, hexagonally-shaped

Question 7

List the different methods used to differentiate polymorphs.

Answer 7

• x-ray diffractometry
• melt behaviour
• raman spectroscopy
• infrared spectroscopy, NMR

Question 8

Describe x-ray diffractometry.

Answer 8

• planes of molecules can give rise to different reflecting layers for x-rays.
• crystalline molecule can cause an incident molecule that has a refracted ray to disperse.
• Use of Bragg’s Law to determine whether diffraction occurs.

Question 9

Describe melt behaviour.

Answer 9

Hot stage microscopy:

• visual characterization of thermal transitions.
• may have in-built sensor for calorimetric measurements.

Differential scanning calorimetry

• enthalpy change is measured as a function of temperature over time.
• crystalline: 1 peak, amorphous: 2 peaks (pick the earlier one).

Question 10

Describe Raman spectroscopy.

Answer 10

• electromagnetic waves incident to crystalline structure will refract and scatter.
• difference in energy of scattered photon with incident photon –> raman scattering.

Question 11

What are the advantages of Raman spectroscopy?

Answer 11

• provide distinct spectroscopic properties
• fast measurement time
• able to measure small spot size