Introduction to Solids: Powders

Question 1

Characteristics of Solids

Answer 1

1) Stable (least amount of kinetic energy)
2) Structural rigidity (resist deformative forces)
3) Definite shape, mass & volume
4) Molecules in solid relatively immobile (oscillate about their mean positions)
5) Mechanically strong & incompressible

Exist in crystalline & amorphous forms

Question 2

Final dosage forms of solids

Answer 2

• Capsules
• Tablets
• Films
• Gums

Question 3

Why solid dosage forms?

Answer 3

1) Better chemical stability
2) Ease of handling, added convenience
3) Lower bulk volume
4) Dry, does not promote microbial growth
5) Flexible, single or multiple chemical components

Question 4

Properties of Mesophase molecules

Answer 4

• Organic
• Elongated/rectilinear molecules
• Rigid molecules
• Possess strong dipoles & easily polarisable groups

Question 5

Type of Mesophase molecules

Answer 5

1) Nematic molecules (Move up & down)
- Thread-like
- Mobile 3D, rotate 1 axis
- orientated with no periodicity

2) Smectic molecules (Move in layers)
- Soap-like, grease-like
- Mobile 2D, rotate 1 axis
- Orientated & arranged in equispaced planes
- No periodicity within planes

Question 6

Classifications of Mesophase molecules

Answer 6

1) Thermotropic (temp-sensitive)

2) Lyotropic (solvent sensitive)

Question 7

Uses of Mesophase molecules

Answer 7

More so in electric industry, not really pharmaceutical

1) Temp sensor
2) Display - liquid crystals provide colours
3) Stabilisation of emulsions, by increasing viscosity (Liquid -> Mesophase)
4) Improve solubilisation of drugs

Question 8

What is polymorphism?

Answer 8

Ability of a solid to exist in more than one form; differences in crystal packing

Chemically similar but have different physical properties (solubility, dissolution, bioavailability, thermal etc.)

Question 9

Crystalline vs Amorphous form

Answer 9

Crystalline:

• Orderly arrangement of constituents
• Anisotropic (has physical order)
• Sharp m.p
• Definite heat of fusion
• Chemically more stable

Amorphous:

• No arrangement
• Isotropic
• Melts over a range
• No definite heat of fusion
• More liable to degradation
• Markedly > soluble (Improved bioavailability)

Question 10

Nanocrystalline form

Answer 10

• Polycrystalline material with a crystalline size of only a few nanometers
• Has areas of crystallinity & areas of non-crystallinity

Properties:
- Improved stability, yet good solubility

Question 11

Methods to determine crystallinity/polymorphism?

Answer 11

1) X-ray diffractometry* (standard)
2) Melt behaviour
3) Raman spectroscopy

Question 12

X-ray diffractometry

Answer 12

• Planes of atoms in molecules give reflecting layers for x-rays
• Diffraction occurs when total path difference = n lambda: 2dsin(0) = n(lambda) by Bragg’s Law
• Peaks are a reflection of the orderliness of crystal (Shaper peak -> More well-ordered)
• Flatter peak can be telling of poorer stability (Amorphous form) -> Orderliness destroyed by grinding

Application: Diffraction pattern allows us to deduce crystal form

Question 13

Melt behaviour

Answer 13

• More orderly crystalline form, sharper melting point

1) Hot stage microscopy
2) Differential scanning calorimetry (DSC)
- Fixed heat input, record enthalpy, a change in phase will take in/ give off more heat (flat line if no change occuring)
- 1st melting point on DSC curve more informative of property

Question 14

Raman spectroscopy

Answer 14

Advantages:

1) Provide distinct spectroscopic property
2) Fast measurement time
3) Able to measure from small spot size (can map distribution of components on tablet)
4) Can measure in presence of H20

Application: Research & identification of material