Drug Solubilisation

Question 1

Process of Solubilisation (3 steps)

Answer 1

• Overcoming the lattice energy of the crystalline solid
• Cavity is created in solvent
• Insertion of solute molecule into solvent, forms solute-solvent interaction

Question 2

Factors influencing aqueous solubility of a solid drug

Answer 2

• Drug-solvent interaction
• Weak electrolytes
• Solubility and dissolution rate

Question 3

Weak electrolytes

Answer 3

• Non/weak electrolytes are common for most organic molecules
• Nonelectrolytes do not dissociate to form ionic species in water
• Solubility of weak electrolytes is highly dependent on the degree of ionisation

Question 4

Major determinants for in vivo drug absorption

Answer 4

• solubility and dissolution rate

Question 5

dissolution rate

Answer 5

function of particle size

Question 6

solubility

Answer 6

function of strength of crystal lattice, and affinity of the drug to aqueous environment

Question 7

3 ways to improve solubilisation of solid drug in aqueous environment

Answer 7

• reduce intermolecular forces in solid state
• increase strength of drug-solvent interaction
• increase surface area available for drug in dissolution

Question 8

Strategies for improving solubilisation of drug (9)

Answer 8

• Optimization of crystal form
• Buffer and salt formation
• Cosolvent
• Surfactant
• Molecular complexation
• Particle size reduction
• Solid dispersion
• Lipid-based formulation
• Nanoparticle drug delivery system

Question 9

Optimization of crystal form - polymorphism and cocrystal

Answer 9

different crystal polymers have different lattice energies

Question 10

What does lower lattice energy mean?

Answer 10

• Lower melting point, better solubility

Question 11

Cocrystal

Answer 11

Consisting of two or more molecular species held together by noncovalent bonds and nonionic forces

Question 12

Buffer/salt formation in parenteral formulation for solubilisation

Answer 12

• Drug in solution form can be achieved via buffer solutions to increase ionisation and drug solubility
• May be impossible for real bioavailability enhancement, as body pH is 5-8
• For weakly basic drugs, precipitation is observed after injection –> low drug concentration

Question 13

When is buffer/salt formation useful?

Answer 13

• Suitable for GI conditions
• Greater solubility in comparison to free acid or base form
• Increase ionisation to increase dissolution rate and solubility
• Increase Cs for passive diffusion