Chemistry Chapter on Ion Behavior

Pharmaceutical Suspension Stability

• Pharmaceutical suspensions are inherently unstable.
• Instability leads to sedimentation.
• Instability leads to particle-particle interactions.
• Instability leads to caking (compaction).

Zeta Potential and Stability

• Most suspended particles in water acquire a charge.
• The charge arises from specific adsorption of ions or ionization of ionizable surface groups (if present).
• If charge arises from ionization, the particle's charge depends on the surrounding environment's pH.
• Zeta potential measures the electrical potential difference between the surface of a particle and the surrounding solution.
• Zeta potential is measured by electrophoretic mobility (movement of particles in an electric field).
• Zeta potential is crucial for stability; high zeta potentials result in particle repulsion, preventing aggregation.

Electrokinetic Properties

• Zeta potential is the difference between the tightly bound layer (shear plane) and the electroneutral region of the solution.

Interaction Between Particles

• Interactions between particles in a liquid medium depend on the distance of separation.
• Three states of interaction are possible:
  • No interaction: Particles are far apart, a thermodynamically stable state.
  • Coagulation (agglomeration): Particles come into close contact, forming an inseparable mass (cake). This is not desirable; the mixture can't be redispersed.
  • Loose aggregation (floccules): Particles aggregate loosely and reversibly, forming flocs that can be redispersed by shaking. This is preferable.

Electrical Properties of Dispersed Particles

• Within an aqueous medium, particles may acquire a charge.
• This charging can be due to ionization of functional groups on the particle, or by adsorption of ions.
• Ionization of groups like COOH or NH2 on insoluble particles depends on the pKa of the molecule and surrounding solution pH.
• Adsorption of Ions: When electrolytes are present, ions can be adsorbed by the particles.
• Preferential adsorption of hydroxyl (OH-) ions can occur in the absence of other electrolytes.

Adsorption of Ions

• Immersion in an electrolyte solution can result in ion adsorption onto particle surfaces.
• Absence of electrolytes leads to preferential adsorption of hydroxyl(OH−) ions.
• These hydroxyl ions are more likely to remain within the bulk medium.
• Adsorption of ions creates an electrical double layer.

Interaction Models

• The DLVO theory explains the interaction between particles.
• The theory accounts for attractive (van der Waals) forces and repulsive forces (electrical double layers).
• The overall interaction energy (V_t) is the sum of attraction (V_a) and repulsion (V_r) energies: Vt = Va + Vr.

Interactions Regions

• Three regions are distinguishable based on particle interaction energy and separation distance:
  • Primary minimum: A region of strong attraction leading to coagulation.
  • Primary maximum: A region of strong repulsion, opposing aggregation. Electrolyte concentration affects this region by decreasing the thickness and hence the strength of the electrical double layer of the particles.
  • Secondary minimum: A region of weak attraction leading to flocculation; the aggregates can be broken apart by shaking.

Diagrammatic Representation

• A diagram shows interaction energy versus separation distance, illustrating the three regions (primary minimum, primary maximum, secondary minimum).