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Solids > Powder > Flashcards

Powder Flashcards

1
Q

Solids

  • Mobility
  • Degree of order
A

Mobility:
Immobile

Degree of order
Anisotropic
Has periodicity & orientation

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2
Q

Liquids

  • Mobility
  • Degree of order
A

Mobility:
Mobile 3D, rotate 3 axes
Move about randomly

Degree of order
Isotropic
No periodicity & orientation

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3
Q

Mesophase

A

State of matter intermediate between solid & liquid

Smectic, nemactic

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4
Q

Smectic phase

  • Mobility
  • Degree of order
A

Mobility:
Mobile 2D, rotate 1 axis

Degree of order:
Anisotropic
Has orientation, arranged in equispaced planes
No periodicity within planes

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5
Q

Nematic phase

  • Mobility
  • Degree of order
A

Mobility:
Mobile 3D, rotate 1 axis

Degree of order
Anisotropic
Has orientation
No periodicity

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6
Q

Properties of mesophase molecules

A

1) Organic
2) Elongated/Rectilinear
3) Rigid
4) Possess strong dipole or easily polarizable groups
- Gives certain orientation

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7
Q

Mesophase molecules are classified as

A

1) Thermotropic (solvent-free)
- Transition by temperature change

2) Lyotropic (with solvent)
- Responsive to solvent

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8
Q

Applications of mesophase molecules

A

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

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9
Q

Characteristics of solids

A

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

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10
Q

Physical properties of solids

A

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

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11
Q

Calculated paths of molecules - Solids

A

Definitive mass, volume, shape
Molecules relatively immobile
- May oscillate in fixed position
Mechanically strong, incompressible

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12
Q

Calculated paths of molecules

A 
No set shape
Flow with relative ease
Molecules move freely, unrestricted 
- Via Brownian motion
- Speed of molecules can be calculated / mapped out
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13
Q

Types of solid oral dosage forms

A

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

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14
Q

Advantages of solid dosage forms

A

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

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15
Q

Structure of solids

A

Crystalline or amorphous

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16
Q

Crystal form

A

Atoms / Ions / Molecules arranged in symmetrical and repeating patterns in 3D
Unit cell: Basic repeating pattern in crystal

17
Q

What is polymorphism

A

Ability of a solid to exist as more than one form/crystal structure

18
Q

Solids form different polymorphs when

A

They are under specific thermodynamic conditions –> so as to minimize crystal lattice energy
E.g. Different polymorphs formed at different temperatures

19
Q

Characteristics of polymorphs

A

1) Chemically similar
2) Different physical properties
- E.g. Solubility, dissolution, bioavailability, morphology thermal
3) Different stability

20
Q

Application in pharmaceutics

A

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

21
Q

Carbon polymorphs

A

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

22
Q

Crystalline VS Amorphous form

1) Arrangement of constituents
2) Degree of order
3) Melting point
4) Heat of fusion
5) Stability
6) Solubility

A

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

23
Q

Preparation methods of amorphous solids

A

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)

24
Q

Nanocrystalline

A

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

25
Q

Developing drug in amorphous VS crystalline form

A

Amorphous form: Better solubility BUT less stable

Must balance between solubility VS stability

26
Q

Determination of crystallinity / polymorphism - Purpose

A

Ensure no change in structure (amorphous to crystalline / between different polymorphs) throughout shelf-life

27
Q

Determination of crystallinity / polymorphism - Methods

A

1) X-ray diffraction
2) Melt behaviour
- Hot stage microscopy
- Differential scanning calorimetry (DSC)
3) Raman spectroscopy
4) NMR spectroscopy
5) Infrared spectroscopy

28
Q

X-ray diffraction - Bragg’s Law

A

2d sinθ = nλ

29
Q

X-ray diffraction - Wavelength used in X-ray diffraction of crystals

A

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

30
Q

X-ray diffraction - How it works

A

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

31
Q

X-ray diffraction - Diffractogram

A

Different polymorphs: Give different diffractogram patterns (different peaks)

Amorphous/Nanocrystalline: No specific pattern/peaks

32
Q

Hot stage microscopy - How it works

A

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
33
Q

Differential scanning calorimetry - How it works

A

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

34
Q

Raman spectroscopy - How it works

A

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
35
Q

Raman spectroscopy - Raman spectra

A

Different polymorphs –> different patterns

Amorphous –> broader, less defined

36
Q

Raman spectroscopy - Advantages

A

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

37
Q

Raman spectroscopy - Applications

A

1) Identification of crystal
2) Composition analysis
- E.g. Determine composition/drug content of tablet
3) Forensic science

Solids (7 decks)

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