Dispersions, Solubility & Dissolution

Dispersion

System where particles of one material are distributed throughout a continuous phase of another

Solution

Homogeneous dispersion; particles 0.01–1 nm; no sedimentation; transparent

Colloid

Dispersion; particles 1–1000 nm; does not separate; translucent/opaque

Suspension

Heterogeneous dispersion; particles >1000 nm; sediment on standing; requires shaking

Solubility

Maximum amount of drug that dissolves in a given volume of solvent at equilibrium

Practically insoluble

Solubility descriptor; ≥10,000 parts solvent needed per 1 part solute

Dissolution

Process by which solid drug passes into solution; prerequisite for oral absorption

Noyes-Whitney equation

Rate of dissolution dm/dt=DA(Cs-C)/H

Diffusion coefficient (D)

Rate at which dissolved molecules move through solvent

Surface area (A)

Exposed area of drug particles; smaller particles → faster dissolution

Saturation concentration (Cs)

Drug solubility at particle surface; constant driving force

Bulk concentration (C)

Drug concentration in surrounding liquid; as CCs, dissolution slows

Diffusion layer (H)

Stagnant solvent layer around particles; thinner → faster dissolution

Ionisation

Dissociation into charged species; ionised form is more water-soluble

Weak acid

Dissociates (HA \rightleftharpoons H^+ + A^-); A- = more soluble ionised form

Weak base

Conjugate acid (BH^+ \rightleftharpoons H^+ + B); BH+ = more soluble ionised form

pKa

pH at which drug is 50% ionised / 50% unionised

Henderson-Hasselbalch equation

Relates pH, pKa and ionisation; pKa=pH+10[HA]/[A-]