Powder Flashcards
Solids
- Mobility
- Degree of order
Mobility:
Immobile
Degree of order
Anisotropic
Has periodicity & orientation
Liquids
- Mobility
- Degree of order
Mobility:
Mobile 3D, rotate 3 axes
Move about randomly
Degree of order
Isotropic
No periodicity & orientation
Mesophase
State of matter intermediate between solid & liquid
Smectic, nemactic
Smectic phase
- Mobility
- Degree of order
Mobility:
Mobile 2D, rotate 1 axis
Degree of order:
Anisotropic
Has orientation, arranged in equispaced planes
No periodicity within planes
Nematic phase
- Mobility
- Degree of order
Mobility:
Mobile 3D, rotate 1 axis
Degree of order
Anisotropic
Has orientation
No periodicity
Properties of mesophase molecules
1) Organic
2) Elongated/Rectilinear
3) Rigid
4) Possess strong dipole or easily polarizable groups
- Gives certain orientation
Mesophase molecules are classified as
1) Thermotropic (solvent-free)
- Transition by temperature change
2) Lyotropic (with solvent)
- Responsive to solvent
Applications of mesophase molecules
1) Temperature sensor (thermotropic)
2) Display - Liquid crystals provide colours
3) Stabilize emulsions by increasing viscosity
4) Improve solubilization of drugs
5) Pharmaceutics –> can make rigid gels/emulsions
Characteristics of solids
1) Solid molecules are closely packed & immobile
2) Least amount of kinetic energy (stable)
3) Structural rigidity, resists deformative forces
- Short intermolecular distance
- Dense & fixed
Physical properties of solids
1) Physical form
- Size, shape, flow
2) Density
3) Melting point
4) Porosity
5) Heat capacity
6) Hardness
7) Deformability
8) Optical properties
9) Wettability
10) Moisture interaction
11) Solubility
Calculated paths of molecules - Solids
Definitive mass, volume, shape
Molecules relatively immobile
- May oscillate in fixed position
Mechanically strong, incompressible
Calculated paths of molecules
No set shape Flow with relative ease Molecules move freely, unrestricted - Via Brownian motion - Speed of molecules can be calculated / mapped out
Types of solid oral dosage forms
Microparticulates
1) Powders
- Crystals, nanoparticles, microcapsules, microspheres
2) Pellets/Spheroids/Beads
3) Granules/Agglomerates
Final dosage forms:
1) Tablets/Caplets
2) Capsules
3) Others e.g. films, gums
Advantages of solid dosage forms
1) Markedly better chemical stability
- Longer shelf-life
2) Lower bulk volume
3) Ease of handling, convenient
4) Does not promote microbial growth (when dry)
5) Flexible
- Allows single or multiple chemical components
Structure of solids
Crystalline or amorphous
Crystal form
Atoms / Ions / Molecules arranged in symmetrical and repeating patterns in 3D
Unit cell: Basic repeating pattern in crystal
What is polymorphism
Ability of a solid to exist as more than one form/crystal structure
Solids form different polymorphs when
They are under specific thermodynamic conditions –> so as to minimize crystal lattice energy
E.g. Different polymorphs formed at different temperatures
Characteristics of polymorphs
1) Chemically similar
2) Different physical properties
- E.g. Solubility, dissolution, bioavailability, morphology thermal
3) Different stability
Application in pharmaceutics
Different polymorphs have different physical properties –> affect therapeutic effect
- E.g. Often prepared as more soluble metastable form –> if change to more stable form –> decrease solubility –> affect bioavailability
Manufacturers must ensure that polymorphic form does not change throughout product life
- E.g. Temperature control throughout supply chain
Carbon polymorphs
1) Diamond
- Tetrahedral structure
- Each C atom is surrounded by 4 other covalently-bound equidisant neighbouring C atoms
- Formed under high temperature & pressure
- Cannot conduct electricity
2) Graphite
- Most stable polymorph
- Hexagonally arranged crystalline form
- Arranged in layers (graphene) that are not covalently bound
- Allows slippage between layers
- Conducts electricity
Crystalline VS Amorphous form
1) Arrangement of constituents
2) Degree of order
3) Melting point
4) Heat of fusion
5) Stability
6) Solubility
Crystalline:
1) Orderly arrangement of constituents; Defined structure
2) Anisotropic; Sharp X-ray diffraction patterns
3) Sharp melting point
4) Defined heat of fusion
5) More chemically stable
- Only surface molecules available for attack
6) Lower solubility
- Less surface area available for dissolution
Amorphous:
1) No arrangement; Irregular, undefined structure
2) Isotropic; No well-resolved X-ray pattern
3) Melts over a range
4) No definite heat of fusion
5) More liable for degradation
6) Markedly more soluble
Preparation methods of amorphous solids
1) Milling (common)
- E.g. Vibratory ball mill
- Difficult to scale up –> limited to small scale operations
- Requires large temperature change (a lot of energy needed)
2) Precipitation
3) Compaction
4) Dehydration
5) Spray drying (common)
6) Supercooling
7) Vapor condensation
8) Freeze-drying (common)
Nanocrystalline
Structure:
Polycrystalline material, with a crystallite size of only a few nanometers
I.e. Amorphous with small area of crystalline structure
Properties:
Good solubility due to amorphous structure
Increased stability due to nanocrystalline spots
Developing drug in amorphous VS crystalline form
Amorphous form: Better solubility BUT less stable
Must balance between solubility VS stability
Determination of crystallinity / polymorphism - Purpose
Ensure no change in structure (amorphous to crystalline / between different polymorphs) throughout shelf-life
Determination of crystallinity / polymorphism - Methods
1) X-ray diffraction
2) Melt behaviour
- Hot stage microscopy
- Differential scanning calorimetry (DSC)
3) Raman spectroscopy
4) NMR spectroscopy
5) Infrared spectroscopy
X-ray diffraction - Bragg’s Law
2d sinθ = nλ
X-ray diffraction - Wavelength used in X-ray diffraction of crystals
Intra-atomic spacing between planes in crystals = A few angstroms (1 - 100 angstroms = 0.1 - 10 nm)
Wavelength used in X-ray diffraction of crystals = 0.1 - 1 nm
X-ray diffraction - How it works
Planes of atoms in molecules give reflecting layers for X-rays
Each atom forms different planes with neighbouring atoms –> each plane can reflect X-rays (different orders of reflection) –> reflection pattern captured in diffractogram
X-ray diffraction - Diffractogram
Different polymorphs: Give different diffractogram patterns (different peaks)
Amorphous/Nanocrystalline: No specific pattern/peaks
Hot stage microscopy - How it works
Visual characterization of thermal transition
- Pulse different amount of heat with time
- Different polymorphs form at different temperatures
- Different polymorphs appear differently under the microscope
May have built-in sensor for calorimetric measurement
- Measure heat uptake
- Any large change –> may indicate change in structure
Differential scanning calorimetry - How it works
Measures enthalpy change as a function of temperature/time
Compare amount of heat required to increase the temperature of a sample/reference
Can detect events (e.g. solid-solid transition, melting point, glass transition, crystallization etc.) that occur over time/change in temperature
- Difference in any of these events indicates different structure
Raman spectroscopy - How it works
Electromagnetic radiation of sample –> absorb energy –> elevated to higher energy level –> lose energy & fall back to lower energy level (vibrational energy state)
When electromagnetic radiation is scattered, one photon of incident radiation is annihilated and, at the same time, one photon of the scattered radiation is created
Rayleigh scattering
- Fall back to initial energy level
- Energy of incident photon = scattered photon
Raman scattering
- Fall back to different vibrational energy level
- Stokes Raman scattering: Higher vibrational energy level VS initial
- Anti-Stokes Raman scattering: Lower vibrational energy level VS initial
- Energy of incident photon ≠ scattered photon
Raman spectroscopy - Raman spectra
Different polymorphs –> different patterns
Amorphous –> broader, less defined
Raman spectroscopy - Advantages
1) Provide distinct spectroscopic property of a material
2) Fast measurement time
3) Able to measure small spot size (up to a few micron)
4) Raman spectroscopy can be done in the presence of moisture
5) Non-destructive
Raman spectroscopy - Applications
1) Identification of crystal
2) Composition analysis
- E.g. Determine composition/drug content of tablet
3) Forensic science
