Medicines 1 - Solubility Enhancement Strategies (basic ppt) (2)

Low Drug Solubility

  • High lipophilicity affects drug absorption.

  • 40% of marketed drugs and 75% of developing compounds have low aqueous solubility.

  • Risks include low and variable drug absorption.

Drug Solubility Examples

  • Piroxicam (20mg): Solubility 7 mcg/mL, requires 2857mL for solubilization, low absorption.

  • Digoxin (0.5mg): Solubility 24 mcg/mL, 21mL volume, good absorption.

  • Griseofulvin (500mg): Solubility 15 mcg/mL, requires 33,333mL, low absorption.

  • Chlorthiazide (500mg): Solubility 780 mcg/mL, 636mL, intermediate absorption.

Solubility Challenges

  • Brick Dust: Hydrophobic & highly intermolecular; poorly soluble in solvents.

  • Grease Balls: Hydrophobic but soluble in non-aqueous solvents.

Strategies to Enhance Solubility

  • Manipulation of pH

  • Salt formation

  • Crystal engineering

  • Particle engineering

  • Co-solvency

  • Solid dispersions

  • Surfactant solubilization

  • Prodrugs

  • Drug derivation

  • Lipid formulations

  • Inclusion complexes

Common Counter Ions in Oral Delivery

  • Basic Counterions: Sodium (65%), Potassium (13%), Calcium (12%).

  • Acidic Counterions: Chloride (57%), Sulphate (8%), Maleate (7%).

Salt Formation and Solubility

  • Different salt forms affect solubility significantly via interactions in the pH-adjusted state.

  • Common examples include Penicillin, Propranolol, and Morphine, showcasing how different salt forms vary in solubility.

Other Considerations in Solubility

  • Common Ion Effect: Physiological ions can suppress the solubility of intended drugs.

  • Use of surfactants and co-solvents in formulations must consider patient safety due to potential irritations and hypersensitivity.

Recent Developments in Solubility Strategies

  • Cocrystals: Mixed crystals enhance solubility through non-covalent bonds without proton exchange.

  • Solid Dispersions: Enhance drug solubility via reduced particle size and increased wettability.

  • Lipid-Based Formulations: Exploit biological lipid uptake pathways for solubilization and absorption.

  • Prodrugs: Modified drugs enhancing solubility and delivery.