powders and solid ( solid state

• Crystals


  • Structure
  • Polymorphism
  • Crystal hydrates
• Powders


  Particle size
• Reduction of particle size

  Affects the dissolution rate by increasing surface area
• Increased surface area


  Increases contact of drug and solvent, dissolution rate, and absorption (fast onset of effect)
• Only a reduction to values below 0.1µm can affect the intrinsic solubility of a drug
• BP can clearly state particle size and particle morphology requirements for some drugs
• Ergotamine aerosol inhalation


  • Most individual particles have a diameter not greater than 5 µm; no individual particle has a length greater that 20µm
• Particle size


  Controls bioavailability, side effects, and toxicity
• Techniques used to reduce particle size have to be chosen taking into account that they can induce changes in crystallinity and compression properties
• Eutectic mixture


  A mixture of two or more components that melt at the lowest temperature possible
• Eutectic mixture


  • 23.3% NaCl solution in water
• Eutectic mixtures


  • Change biopharmaceutical properties of poorly soluble or wettable drugs
  • Change the crystallinity of the drug so much as to modify intrinsic solubility and rate of dissolution
• How eutectic mixtures can improve drug solubility

  1. Reduction in particle size (microcrystals)

  2. Absence of particle aggregation

  3. Solubilisation effect of the carrier

  
• Eutectic mixtures


  • Griseofulvin + succinic acid (25:75)
  • Cholarmphenicol + urea
  • Sulphatiazole + urea
  • Niacinamide + ascorbic acid
  • Procaine + lidocaine (50:50)