Physical Pharmacy: Intramolecular and Intermolecular Forces

Attractive Forces in Molecules

• Intramolecular Forces: Involve electron sharing; can be polar (unequal sharing creates partial charges) or non-polar (equal sharing).
• Polar molecules exhibit affinity between oppositely charged particles and can involve electron transfer.
• Intermolecular Forces (IMFAs):
  • Energy ranges from 0.5 to 7 kcal/mole depending on interactions:
    • Polar-polar: 1-7 kcal/mole
    • Polar-nonpolar: 1-3 kcal/mole
    • Nonpolar-nonpolar: 0.5-1 kcal/mole
• Cohesion vs Adhesion:
  • Cohesion: attraction among similar molecules.
  • Adhesion: attraction among different molecules.

States of Matter

• Plasma State: Supercritical fluid state, intermediary between liquid and gas.
• Liquid State:
  • Dispersed systems classified into three categories based on particle size:
    • Homogenous molecular dispersion (< 1 nm).
    • Intermediate systems (1 nm – 0.5 µm).
    • Coarse dispersions (> 0.5 µm), includes emulsions and suspensions.

USP Terms of Solubility

• Colligative Properties of Solutions:
  • Vapor Pressure Lowering: Non-volatile solute addition reduces solvent vapor pressure based on solute concentration.
  • Boiling Point Elevation: Non-volatile solutes elevate boiling point above that of pure solvent due to lowered vapor pressure.
  • Freezing Point Depression: Solutions have lower freezing points compared to pure solvents.
  • Osmotic Pressure: Solutions exert higher osmotic pressure than pure solvents, defined as the pressure to prevent osmosis through a semipermeable membrane.

Interfacial Phenomenon

• Related to molecules at phase boundaries.
• Interfacial Tension: Occurs in liquid-liquid systems.
• Surface Tension: Present in solid-liquid and liquid-gas systems.
• Surfactants: Also known as surface-active agents, alter surface and interfacial tensions.

Colloidal Dispersions

• Properties of Colloids:
  • Optical: Exhibits the Faraday-Tyndall effect, which scatters light (e.g., fog).
  • Kinetic: Brownian movement, where particles appear as moving light points; diffusion balances concentration.
  • Electric:
    • Nernst Potential: Potential difference between particle surfaces and surrounding neutral regions.
    • Zeta Potential: Difference in potential impacting pharmaceutical applications.

Coarse Dispersion

• Stability issues present challenges in formulation.

Rheology

• Viscosity (ƞ): Resistance to flow, characterized by multiple classes:
  • Absolute, Kinematic, Relative viscosity distinctions.
• Viscometers: Instruments used to measure viscosity.
• Flow Systems:
  • Newtonian Flow: Consistent viscosity regardless of shear rate.
  • Non-Newtonian Flow: Viscosity varies with shear rate:
    • Shear-dependent: Plastic, Pseudoplastic, Dilatant.
    • Time-dependent: Thixotropy, Rheopexy.

Micromeritics

• Particle Size Determination Methods:
  • Optical Microscopy, Sieve Analysis, Sedimentation Method, Automatic Particle Counters (Coulter, HIAC/Royco, Gelman).
• Particle Volume: Total space occupied by powder calculated as Vb = Vp + intra + inter-spaces.
• Particle Density: Measure of mass per unit volume.
• Porosity (ϵ): Total voids/spaces in particles.
• Properties for Granulation:
  • Fluidity: Ability of powder to flow.
  • Compressibility: Capacity to reduce volume under pressure.