Powders Flashcards
- Describe the organisation of the constituents in solids (anisotropic and isotropic I guess) - What are the major characteristics of solids? - Why are most drugs delivered via the solid dosage forms? - Explain polymorphism (crystalline and amorphism) and the characteristics of polymorphs. - Explain the importance of polymorphism in pharmaceutics (amorphism, improve solubility) - Describe the methods to differentiate polymorphs (Raman, X-ray, DSC)
What is the Solid mobility and degrees of order?
- Immobile
- Crystalline, has orientation and periodicity
anisotropic
What is the Smectic mobility and degrees of order?
Soap-like, Grease-like
Mobile 2D, rotate 1 axis; Orientated and arranges in equispaced planes, no periodicity within planes
anisotropic, mesophase
What is the Nematic mobility and degrees of order?
Thread-like
Mobile 3D, rotate 1 axis, orientated with no periodicity
anisotropic, mesophase
What is the liquid mobility and degrees of order?
Mobile 3D, rotate 3 axes
Isotropic fluid, no orientation nor periodicity
What are the properties of mesophase (smectic and nematic) molecules?
- Organic molecules
- Elongated or rectilinear molecules
- Rigid molecules
- Possess strong dipoles and easily polarisable groups
How are mesophase (smectic and nematic) molecules classified as?
- Thermotropic (solvent-free); transition by temp change; its order is affected by temp
- Lyotropic (forms liquid crystal phases with solvent)
What are the uses of mesophase (smectic and nematic) molecules?
- Temp sensor
- Display - liquid crystals provide colours
- Stabilisation of emulsions,
- Improve solubilisation of drugs
What are the solid dosage forms (oral)?
- Multi-particulates (powders, granules/agglomerates, pellets/spheroids/beads)
- Final dosage form: capsules, tablets, others (films, gums)
Why are solid dosage forms preferred?
- 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
What are crystals?
ordered structures, repeating patterns in 3D
Basic repeating pattern is the unit cell of the structure
What is polymorphism?
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
What is the difference btw crystalline and amorphous state?
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
How to develop an amorphous state?
- milling
- compaction
- dehydration
- vapor condensation
- spray drying
- precipitation
- supercooling
- freeze drying
What is the amorphous state?
Amorphous state: Amorphous and Nanocrystalline
Amorphous: improves drug solubility (90% of drugs in industry are poorly water soluble)
Nanocrystalline: improved stability + good solubility
How do determine crystallinity or polymorphism? What methods can we use?
- x-ray diffractometry (STANDARD METHOD)
- Melt behaviour (visual - hot stage microscopy; differential scanning calorimetry)
- Raman spectroscopy
Others: IR spectroscopy; NMR spectroscopy (not for pharmaceutical)
How does x-ray diffractometry works?
Question: What kind of compounds will not produce sharp peaks in powder x-ray diffractograms?
- 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
What is the Bragg’s Law?
Total path difference 2d sin (tether) = n (lambda), diffraction occurs
d= distance of plane n = order of reflection
What is Melt behaviour (visual - hot stage microscopy)?
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
What is Melt behaviour (differential scanning calorimetry - DSC)?
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)
What is the concept of Raman spectroscopy?
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
Advantages of using Raman spectroscopy?
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
