Drug Dissolution Processes

Preformulation- Dissolution

• This topic concerns the dissolution of drugs.
• Drug dissolution is vital for the absorption of most drugs.
• Drugs in capsules and tablets need to dissolve in gastrointestinal fluids.
• Dissolution is a dynamic process, unlike solubility which is static.
• Drug dissolution can be measured using techniques like beaker method, flask stirrer method, rotating basket method, paddle method, and flow-through-cell.
• Factors affecting drug dissolution include agitation, viscosity, particle size, wettability, porosity, crystalline form, saturation solubility, volume of solution, and excipients.

Drug Dissolution

• Matter exists as solid, liquid, and gas.
• Melting changes a solid to a liquid using heat.
• Solubility is the mass of solute dissolving in a specific mass or volume of solvent at a given temperature.
• Dissolution is the process where a solid drug substance becomes dissolved in a solvent.

Melting

• Melting point (m.p.) is the temperature at which a solid transforms into a liquid.
• Melting necessitates heat.
• Heat of fusion (ΔH) is the heat absorbed or released when a system changes its thermodynamic state.
• Aspirin has a melting point of 135°C and a heat of fusion of 45.52 cal/g.
• Palmitic acid has a melting point of 63°C and a heat of fusion of 39.18 cal/g.

Importance of Drug Dissolution

• Most drugs need to dissolve in bodily fluids before absorption.
• Drugs in solid dosage forms (like capsules and tablets) must undergo dissolution in the gastrointestinal tract.

Dissolution Process

• During dissolution, the starting solid drug disintegrates and deaggregates into individual drug particles.
• ΔH (enthalpy change) accompanies solid dissolution in a solvent. ΔH = ΔH₁ + ΔH₂ + ΔH₃ where ΔH₁ is the separation of solute particles, ΔH₂ is the separation of solvent particles, and ΔH₃ is the interaction between the solute and solvent.
• Dissolution involves steps on the molecular level, including separating solute, separating solvent, and solute-solvent interaction.
• Exothermic process: -2U_sL > U_ss+U_Ll
• Endothermic process: -2U_sL < U_ss+U_Ll

Dissolution Methods, Noyes-Whitney Equation, and Dissolution Testing

• Drug dissolution rate is often described using the Noyes-Whitney equation: dC/dt = k • A(CS - CB) where

• dC/dt = rate of drug dissolution

• k = dissolution rate constant (D/h)

• A = surface area

• CS = saturation solubility of the drug

• CB = concentration of the drug in the bulk solution

• D = diffusion coefficient

• h = thickness of diffusion layer.

• Different methods (beaker, flask stirrer, rotating basket, paddle, flow-through-cell) are used for dissolution testing.

Sink Conditions

• Sink conditions refer to situations where CB (concentration of drug in the bulk solution) is significantly much smaller than CS (saturation solubility of the drug in the dissolution medium).
• Non-sink conditions involve a drug concentration near or exceeding its saturation solubility.

Factors Affecting Drug Dissolution

• Factors like particle size, agitation, viscosity, and excipients influence drug dissolution rates.

Polymorphism

• Polymorphism can impact drug solubility.
• Metastable polymorphs demonstrate faster dissolution rates compared with stable polymorphs.