SOLID-STATE CHARACTERIZATION

• Powders


  • Masses of solid particles or granules surrounded by air (or other fluid)
  • Solid plus fluid combination significantly affects the bulk properties of the powder
  • The most complicating characteristic because the amount of fluid can be highly variable
  • Least predictable of all materials in relation to flow ability because of the large number of factors that can change their rheological properties
• Physical characteristics of powder particles

  • Size
  • Shape
  • Angularity
  • Size variability
  • Hardness
• External factors influencing powder behavior

  • Flow rate
  • Compaction condition
  • Vibration
  • Temperature
  • Humidity
  • Electrostatic charge
  • Aeration
  • Transportation experience
  • Container surface effects
  • Storage time
• Energy dispersive X-ray spectrometry (EDS)


  Quick and easy elemental analysis of samples in the SEM, minimum detection limit of 0.1% by weight
• Wavelength dispersive X-ray spectrometry (WDS)


  More detailed elemental analysis of samples in the SEM, minimum detection limit of 0.01% by weight, fully quantitative results
• Inductively coupled plasma-atomic emission spectroscopy (ICP)

  Trace level and bulk elemental analyses of solid and liquid samples, minimum detection limits better than 1 ppb by weight
• Surface analysis (AES/XPS)


  Electron spectroscopy for elemental analysis of surfaces, sensitive to as low as two atomic layers
• Scanning electron microscopy


  For high resolution and high magnification photographs
• Thermal analysis techniques


  • DSC
  • TGA
  • TMA
  • Dynamic mechanical analysis
• Thermal analysis determines calorimetric and mechanical properties, such as heat capacity, mechanical modulus, sample mass, and dimensional changes in temperature ranges between 21508C and 16008C
• Microthermal analysis


  Combines the principles of scanning probe microscopy with thermal analysis via replacement of the probe tip with a thermistor, allows spatially scanning samples in terms of both topography and thermal conductivity
• Particle size is important as it can affect the formulation characteristics and bioavailability of a compound
• Sedimentation and flocculation rates in suspensions are, in part, governed by particle size
• Inhalation therapy of pulmonary diseases demands that a small particle size (2–5 _m) is delivered to the lung for the best therapeutic effect
• Particle size can be very important for good homogeneity in the final tablet
• Grinding in a mortar and pestle, ball milling or micronization can be used to reduce the particle size
• Prolonged ball milling may be detrimental in terms of compound crystallinity and stability
• Ball milling may change the polymorphic form of a compound
• Bulk density


  The density of a powder sample, includes both the particulate volume and the pore volume
• Minimum bulk density


  When the volume of the powder is at a maximum, caused by aeration, just prior to complete breakup of the bulk
• Poured bulk density


  When the volume is measured after pouring powder into a cylinder, creating a relatively loose structure
• Tapped bulk density


  The maximum bulk density that can be achieved without deformation of the particles
• Porosity


  The proportion of a powder bed or compact that is occupied by pores, a measure of the packing efficiency of a powder
• Relative density


  The ratio of the measured bulk density divided by the true density
• Good flow properties are a prerequisite for the successful manufacture of both tablets and powder-filled hard gelatin capsules
• The resistance to differential movement between particles is due to the cohesive forces between particles, including electrostatic charging, van der Waals forces and forces due to moisture
• Powder compaction


  The process of converting a loose incoherent mass of powder into a single solid object
• When a powder bed is subjected to further compression beyond its tapped bulk density, the particles will deform elastically to accommodate induced stresses, and the density of the bed will increase with increasing pressure at a characteristic rate
• When the elastic limit is exceeded, there is a change in the rate of reduction in the bed volume as plastic deformation or brittle fracture of particles begins
• Capping and lamination


  Occurs when a material is unable to relieve stresses present within a compact following compression by plastic deformation
• The ratio of axial to radial tensile strength should be close to unity for a good formulation to avoid capping and lamination