Powders

Question 1

What is the Solid mobility and degrees of order?

Answer 1

• Immobile
• Crystalline, has orientation and periodicity

anisotropic

Question 2

What is the Smectic mobility and degrees of order?

Answer 2

Soap-like, Grease-like
Mobile 2D, rotate 1 axis; Orientated and arranges in equispaced planes, no periodicity within planes

anisotropic, mesophase

Question 3

What is the Nematic mobility and degrees of order?

Answer 3

Thread-like
Mobile 3D, rotate 1 axis, orientated with no periodicity

anisotropic, mesophase

Question 4

What is the liquid mobility and degrees of order?

Answer 4

Mobile 3D, rotate 3 axes

Isotropic fluid, no orientation nor periodicity

Question 5

What are the properties of mesophase (smectic and nematic) molecules?

Answer 5

• Organic molecules
• Elongated or rectilinear molecules
• Rigid molecules
• Possess strong dipoles and easily polarisable groups

Question 6

How are mesophase (smectic and nematic) molecules classified as?

Answer 6

• Thermotropic (solvent-free); transition by temp change; its order is affected by temp
• Lyotropic (forms liquid crystal phases with solvent)

Question 7

What are the uses of mesophase (smectic and nematic) molecules?

Answer 7

• Temp sensor
• Display - liquid crystals provide colours
• Stabilisation of emulsions,
• Improve solubilisation of drugs

Question 8

What are the solid dosage forms (oral)?

Answer 8

• Multi-particulates (powders, granules/agglomerates, pellets/spheroids/beads)
• Final dosage form: capsules, tablets, others (films, gums)

Question 9

Why are solid dosage forms preferred?

Answer 9

• markedly better chemical stability
• when dry, doesn’t promote microbial growth
• lower bulk vol
• ease of handling, added convenience
• flexible, single or multiple chemical components

Question 10

What are crystals?

Answer 10

ordered structures, repeating patterns in 3D

Basic repeating pattern is the unit cell of the structure

Question 11

What is polymorphism?

Answer 11

Chemically similar but diff physical properties (solubility, dissolution, bioavail, morphology, thermal, etc.) can vary btw polymorphs

> 1 form of crystal structure; differences in crystal packing

polymorphs exist: minimise their crystal lattice energy

Question 12

What is the difference btw crystalline and amorphous state?

Answer 12

Crystalline:

• orderly arrangement of constituents, defined structures
• ANISOTROPIC, sharp x-ray diffraction patterns
• sharp m.p.
• definite heat of fusion
• more stable, chemically

Amorphous:

• no arrangement; irregular/ undefined shapes
• ISOTROPIC, no well-resolved x-ray patterns
• melt over a range
• no definite heat of fusion
• more liable to degradation
  solubility: markedly MORE SOLUBLE

Question 13

How to develop an amorphous state?

Answer 13

• milling
• compaction
• dehydration
• vapor condensation
• spray drying
• precipitation
• supercooling
• freeze drying

Question 14

What is the amorphous state?

Answer 14

Amorphous state: Amorphous and Nanocrystalline

Amorphous: improves drug solubility (90% of drugs in industry are poorly water soluble)

Nanocrystalline: improved stability + good solubility

Question 15

How do determine crystallinity or polymorphism? What methods can we use?

Answer 15

1. x-ray diffractometry (STANDARD METHOD)
2. Melt behaviour (visual - hot stage microscopy; differential scanning calorimetry)
3. Raman spectroscopy

Others: IR spectroscopy; NMR spectroscopy (not for pharmaceutical)

Question 16

How does x-ray diffractometry works?

Question: What kind of compounds will not produce sharp peaks in powder x-ray diffractograms?

Answer 16

• Planes of atoms in molecules give reflecting layers for x-rays
• Uses Bragg’s Law

X-ray: 0.01-10nm (for crystallography: powder diffraction ~0.1nm)

Intra-atomic spacing btw planes in crystals typically a few angstrom; 1-100 angstroms (0.1-10nm)

Answer: Amorphous compounds

Question 17

What is the Bragg’s Law?

Answer 17

Total path difference 2d sin (tether) = n (lambda), diffraction occurs

d= distance of plane
n = order of reflection

Question 18

What is Melt behaviour (visual - hot stage microscopy)?

Answer 18

Visial characterisation of thermal transitions; may also have in-built sensor for calorimetric measurement

Used for diagnosis of mixed crystals

Orderly crystalline form : have sharp mp

Question 19

What is Melt behaviour (differential scanning calorimetry - DSC)?

Answer 19

Measure enthalpy change as a function of temp or time; difference in the amt of heat required to inc the temp of a sample and reference

Tg: glass transition
Tc: crystalisation
Tm: melting

Fixed amt of heat per unit time

Orderly crystalline form : have sharp mp; only one m.p.

Amorphous: Amorphous form re-crystallise to crystalline form
Thus melt at 2 melting points (one m.p. earlier than the crystalline form and one with the crystalline form)

Question 20

What is the concept of Raman spectroscopy?

Answer 20

When EM radiation is scattered, one photon of incident radiation is annihilated and, at the same time, one photon of the scattered radiation is created.

If the energy of the incident photon = the scattered one –> Rayleigh scattering.

If energy of incident photon is different to that of the scattered one –> Raman scattering

Question 21

Advantages of using Raman spectroscopy?

Answer 21

a) Provide distinct spectroscopic property of a material
b) fast measurement time (VS x-ray as x-ray takes more time)
c) able to measure from small spot size, to a few microns

Uses: in non-destructive, microscopic, chemical analysis applications