SOLIDS

• Solid Dosage Forms


  • Methods and Techniques
  • Equipment
  • Standards/Quality Control Test
• Solid dosage forms


  • Powders
  • Tablets
  • Capsules
• Large-Scale Methods & Techniques in Formulating Powders

  1. Mechanical Mixing

  2. Tumbling

  3. Pulverization

  4. Geometric Dilution
• Mechanical Mixing


  Mixer should produce a complete blend rapidly to avoid product damage, should be cleaned and discharge easily, dust-tight and low maintenance and power consumption
• Tumbling


  Another method of mixing powders, time consuming
• Pulverization


  Crushing powders to reduce particle size
• Geometric Dilution


  Addition of substance that is equal to the amount in the equipment, method of choice for potent substances
• Powder Characterisation Techniques


  • Powder Rheology
  • Moisture Content
  • Surface Area Determination by BET
  • Particle Size
  • Particle Shape and Morphology
• Powder Rheology


  Pharmaceutical processing, filling, packaging, bioavailability, particle size & compressibility
• Moisture Content


  Quantity of water present in the powder, affects stability and shelf-life
• Surface Area Determination by BET


  Absorption method, larger than surface area determined by air permeability
• Particle Size


  Size of the powder, determined by sieve analysis
• Particle Shape and Morphology

  Influences the physicochemical properties of a powder, affects the flow rate and compressibility
• Angle of Repose


  Inverse measure of flowability, higher angle = lower flowability
• Hausner's Ratio, Carr's Index


  Measures of powder flowability
• Particle Sizing Techniques


  1. Quantitative Separation by Inertial Methods

  2. Diffraction of Laser Light

  3. Imaging
• Quantitative Separation by Inertial Methods

  Dependent on the force generated by secondary flows such as stokes drag force along with inertial lift force, examples include impactor and analytical sieving
• Diffraction of Laser Light


  Commonly used technique, affected by Tyndall effect in colloids, examples include static and dynamic laser-light scattering
• Imaging


  Used for both size distribution and morphology of particles, examples include optical microscopy and scanning electron microscopy
• Large-Scale Methods & Techniques in Formulating Powders

  1. Tumbler Machine

  2. Ribbon Blender
• Tumbler Machine


  Suitable for blending dry powder material, the rotation of the barrel causes the mass to tumble down upon itself causing friction and thereby abrading the parts in the mass
• Ribbon Blender


  Widely used for the manufacture of dry powder, mixes free-flowing raw materials within a U-shaped trough using a horizontal agitator consisting of precisely pitched inner and outer helical ribbons
• Quality Control Tests for Powders


  • Particle Size
  • Moisture Content
  • Percentage Fines
  • Angle of Repose
  • Compressibility Index
• Particle Size


  Measured using coulter counter principle, laser diffraction, and microtrac model
• Moisture Content


  Typically less than 4%, 1% in US
• Percentage Fines


  Should not be more than 15%
• Angle of Repose


  Less than 25 = Excellent, Greater than 40 = Poor
• Compressibility Index


  1. 15% = Excellent Flow, 12-16% = Very Good Flow, 18-21% = Good Flow, 23-25% = Passable Flow, 33-38% = Poor Flow, >40% = Very Poor Flow
• New Large-Scale Methods & Techniques in Formulating Tablets

  1. Pneumatic Dry Granulation (PDG)

  2. Reverse Wet Granulation

  3. Steam Granulation

  4. Moisture-Activated Dry Granulation (MADG)

  5. Direct Compression
• Pneumatic Dry Granulation (PDG)


  An innovative dry granulation technology, utilizes roller compaction together with a propriety air classification method to produce granules with extraordinary combination of flowability and compressibility
• Reverse Wet Granulation


  Also known as reverse-phase wet granulation, involves the immersion of the dry powder formulation into the binder liquid followed by controlled breakage to form granules
• Steam Granulation


  A new wet granulation technique, water steam is used as binder instead of traditional liquid water as granulation liquid
• Moisture-Activated Dry Granulation (MADG)

  A variation of conventional wet granulation technique, uses a very little water to activate a binder and initiate agglomeration
• Direct Compression


  Tablets are compressed directly from powder blends of APIs and excipients, hard as rock but can be dissolved
• Quality Control Tests for Tablets

  • Color
  • Odor
  • Thickness test
  • Hardness test
  • Friability Test
  • Weight Variation Test
  • Disintegration Test
  • Content Uniformity test
  • Dissolution Test
• Color


  Vital means of rapid identification and consumer acceptance, mottling could indicate stability problems
• Odor


  Vital means of rapid identification and consumer acceptance
• Thickness test


  Should be controlled within 5% variation of standard value for consumer acceptance and to facilitate packaging
• Hardness test


  Force required to break a tablet in a diametric compression test, to withstand mechanical shocks of handling in manufacture, packaging, shipping
• Friability Test


  Measures how much mechanical stress tablets are able to withstand during manufacture, distribution, handling