physical behaviour of drug solids

• What results in a solid state of matter?

  Attractive forces exceed repulsive forces
• What is a dipole-dipole interaction?

  Interaction between areas of electron density
• What is the role of hydrophobic interactions in proteins?

  They fold proteins to hide hydrophobic side chains
• What defines solubility?

  Maximum concentration that dissolves in solvent
• Why is solubility important for drugs?

  It governs bioavailability
• What does a high dissolution rate indicate?

  Potential absorption characteristics of a drug
• How does melting point relate to solubility?

  Lower melting point indicates greater solubility
• What is the melting point of aspirin?

  135 °C
• What is the melting point of morphine?

  250 °C
• How does melting point affect drug solubility?

  • >300°C: Major factor
  • >200°C: Probably factor
  • 100-200°C: Equivocal factor
  • <100°C: Not a factor
• What are the definitions of solid states?

  • Amorphous solids: Disordered arrangements, no crystal lattice
  • Crystalline solids: Regular arrangement in a crystal lattice
• What is a crystal lattice?

  Orderly 3D arrangement of molecules
• What are the most common unit cells for drugs?

  Triclinic, monoclinic, orthorhombic
• What factors influence crystal habit?

  • Flow
  • Dispersibility
  • Aerodynamics
  • Dissolution
  • Solubility
  • Bioavailability
  • Compressibility
• What is nucleation in crystal formation?

  Process by which a crystal forms
• What is polymorphism in pharmaceuticals?

  Molecules arrange in more than one pattern
• What are the implications of polymorphism in drugs?

  • Formulation concerns
  • Therapeutic implications
  • Legal issues
  • Commercial implications
• What happened with ritonavir in 1998?

  It failed dissolution tests and was withdrawn
• What is the effect of hydration on drug solubility?

  Hydrates often reduce aqueous solubility
• What are the types of hydrates in drugs?

  • Monohydrates: Drug:Water 1:1
  • Dihydrates: Drug:Water 1:2
• What is the impact of crystal change on drug properties?

  It affects energy, rigidity, and bioavailability
• What does interfacial tension define in crystal growth?

  It influences the rate of crystallization
• What is the significance of amorphous solids?

  • They lack a defined crystal structure
  • They can have different solubility characteristics
• What can co-crystals do compared to polymorphs?

  Be more stable and reduce stability concerns
• What is the use of solids in solid behavior?

  To alter solubility and solution rate
• What are the three outcomes when mixing solids?

  1. Coarse physical suspension
  2. Solid in solid
  3. Eutectic mixture
• What is a eutectic mixture?

  Cooled molten mixture
• How do hydrates affect aqueous solubility?

  They often reduce aqueous solubility
• What happens to each lattice type over time?

  They convert to the lowest energy form
• What is the effect of hydration on oxyphenbutazone dissolution?

  Hydrates are more stable, reducing solubility
• What is the role of interfacial tension in crystal growth?

  It defines how crystals grow
• What are the characteristics of amorphous solids?

  • No long-range order
  • Lower melting point
  • Better solubility than crystalline forms
  • Poor flowability
• What processes can convert crystalline solids to amorphous forms?

  Micronisation, milling, freeze drying, spray drying
• What is the glass transition temperature (Tg)?

  Temperature where material is glassy and brittle
• How do amorphous materials differ from crystalline materials in melting behavior?

  Amorphous materials melt over a large range
• What happens to drugs in amorphous form compared to crystalline form?

  They have greater solubility
• What is the particle size range in dosage forms?

  • DPI: 0.1 µm
  • Tablets: 1000 µm
  • Oral suspensions: 10-50 µm
  • Parenteral suspensions: 0.5-25 µm
• How does decreasing particle size influence dissolution rate?

  It increases the dissolution rate
• What is the effect of particle size on drug absorption?

  Must be in solution to be absorbed
• What is the relationship between particle size and controlled release?

  Particle size plays a critical role