midterm

• Tablet friability test


  Also known as: tablet drop test, tablet abrasion test
• Friability


  A tablet property related to hardness. It is the ability to withstand abrasion in packaging, handling and shipping. It is defined as the % of weight loss by tablets due to mechanical action during the test. Refers the ability of the compressed tablet to avoid fracture and break during transport.
• Principle of the tablet friability test

  Induces self-abrasion to the tablets, as it falls 6 inches on each turn of the friabilator drum
• Time setting for tablet friability test

  5 minutes or 4 minutes (equivalent to 100 rpm)
• USP specifications for tablet friability

  Not more than 1% or from 0.5% to 1% for existing formulations, not more than 0.8% for new formulations
• Roche friabilator


  An instrument used to measure tablet friability
• Manual tablet friability testers, PTF 10ER/20ER


  Tablet friability test instruments manufactured in compliance to the USP, European and other pharmacopoeias. They have 1 or 2 drums made from Plexiglass (perspex) that rotate at a programmable speed and time.

  
• Types of friabilator drums

  • Traditional Roche (single chamber), Vankel-type, Abrasion type with internal baffles/lamellas
• Tablet thickness can vary with no change in weight due to difference in density of granulation, the pressure applied to the tablets, and the speed of tablet compression
• Tablet thickness


  Refers to the depth or extent from one surface to another surface
• Tablet thickness should be controlled within +/-5% variation, based on the standard measurement of thickness and diameter of the product
• Equipment for measuring tablet thickness

  Vernier caliper, thickness gauge, micrometer caliper

  
• Micrometer caliper


  An instrument that measures the thickness or the diameter of relatively small parts and produces finer results than a vernier caliper

  
• Parts of a micrometer caliper

  • Ratchet knob, frame, anvil, finely threaded screw, thimble, spindle, lock nut

  
• Vernier caliper


  An instrument that measures the external diameter of a tube or container, and the internal diameter of objects

  
• Parts of a vernier caliper


  • Vernier scale, ears/upper jaw, lower jaw, main scale, tail
• Oral liquids are homogeneous liquid preparations, usually consisting of a solution, an emulsion, or a suspension, of one or more active ingredients in a suitable liquid base
• Visual inspection of solutions


  Inspect for clarity, freedom from precipitate, discoloration or cloudiness which may indicate chemical degradation or microbial contamination

  
• Visual inspection of suspensions

  Evidence of physical instability is demonstrated by the formation of flocculants or sediments that do not readily disperse on gentle shaking. Discoloration may indicate chemical degradation or microbial contamination.

  
• Visual inspection of drops

  Drops that are solutions should be clear and free from any precipitate. Evidence of physical instability of drops that are suspensions is demonstrated by the formation of flocculants or sediments that do not readily disperse on gentle shaking. Evidence of physical instability of drops that are emulsions is demonstrated by phase separation that is not readily reversed on gentle shaking.
• Visual inspection of granules


  Evidence of physical instability is demonstrated by noticeable changes in physical appearance, including texture (ex. clumping of granules, presence of loose powder). Discoloration may indicate chemical degradation or microbial contamination.
• Quality control tests for solutions

  • Visual inspection, rheological studies, pH determination, zeta potential, sedimentation volume, redispersability test
• Rheological studies


  Tests for flowability [fluidity] and viscosity, can be determined with Brookfield or Cone and plate Viscometers

  
• Zeta potential


  Governs the degree of repulsion between adjacent similarly charged dispersed particles, a higher zeta potential is more desirable as suspensions tend to have a slower rate of settling
• High sugar concentrations cause bacteria to lose water by osmosis and they can't pump it back in against the osmotic gradient, so they can't grow or divide
• Sedimentation volume (F)


  The ratio of the ultimate volume (Vu) of the sediment to the original volume (Vo) of the suspension. The larger this ratio, the better is the redispersibility.
• Redispersability test


  Refers to the amount of force to redisperse or resuspend the particles, the requirement is that no sediment should remain at the base after shaking
• Redispersibility


  Describes the ease of redispersion of the formed sediment by moderate shaking to yield a homogenous system
• Particle size changes


  Any change in the particle size of the suspension can give an indication of crystal growth, can be measured by microscope, Coulter counter device, or laser diffraction device

  
• Freeze-thaw cycling technique


  Applicable to stress the suspension to promote crystal growth, involves quickly freezing at -85°C and thawing at 4°C in sequence

  
• Cobalt chloride test


  When a filter paper soaked in cobalt chloride solution is dipped into an emulsion and dried, it turns from blue to pink, indicating that the emulsion type is o/w type
• Spreading test


  Water in oil type emulsion spread on the surface of oil but not on the surface of the water
• Appearance of granules


  The general appearance of a granule, its identity and general elegance is essential for components in manufacturing, for control of lot-to-lot uniformity and tablet-to-tablet uniformity
• Density of granules


  May influence compressibility, tablet porosity & dissolution. Dense hard granules may require higher load to produce cohesive compacts
• Particles


  Assessed individually. To obtain adequate sensitivity, the volume of liquid measured must be similar to the volume of the particle
• Emulsion test


  1. Filter paper soaked in cobalt chloride solution is dipped into an emulsion and dried

  2. Turns from blue to pink, indicating that the emulsion type is o/w type
• CHAPTER 03: COMPENDIAL REQUIREMENTS FOR GRANULES
• Appearance of granules


  • Identity and general elegance is essential for components in manufacturing, for control of lot-to-lot uniformity and tablet-to-tablet uniformity
  • Involves the measurement of size, shape, color, presence or absorbance
• Density


  • May influence compressibility, tablet porosity & dissolution
  • Dense hard granules may require higher load to produce cohesive compact to reduce free granules seen on the surface of tablets
• Increased compressibility


  Increases disintegration time, dissolution (if disintegration time is slower, dissolution is indirectly hampered)