L18 - Drug Solubility and Dissolution Rate 3

• What's the typical dosage form for a class I drug?

  solid oral dosage form eg tablet - high permeability and high solubility already

  
• How can we increae solubility of a class II drug?

  - increase SA (reduce particle size)- use surfactants to form micelles

  
• How can we increase permeability of class III drugs?

  - add permeability enhancers- maximise luminal conc

  
• Where are weak acids/bases more likely to be absorbed and why?

  Weak bases = more soluble at lower pHs as more ionised (eg stomach)Weak acids = more soluble in higher pHs as more ionised (eg small intestine)

  
• How does using salt form increase solubility?

  - Salt is a strong electrolyte so increases polarity- control pH of diffusion layer irrespective of location in GI tract, so increase dissolution rate and increase solubility

  
• What's the pH of diffusion layer equal to if we use a) free acid and b) salt form?


  a) = to bulk solutionb) = to the salt
• Precipitation


  The process of a solid substance forming from a solution.
• What is cosolvency?

  When a second solvent is mixed with the first solvent to improve solubility
• How can cosolvents increase solubility and dissolution rate?

  Can decrease surface tension by decreasing polarity of waterCosolvents have lower polarity than water.They decrease Hydrogen bond density, reducing polarity which reduces cohesion of water molecules, making systems more thermodynamically unstableEg, mixing water decreases polarity of water, so keeps non-polar molecules inside

  
• How do we measure polarity of water?What's the relationship between dielectric constant and polarity?

  Using the dielectric constant- the lower the dielectric constant, the lower the polarity

  
• What must cosolvents be to increase solubility?What are some examples?

  1) Organic molecules2) miscibie with water3) Better solvents than water for the drug:- H bond donor and acceptor groups- small hydrocarbon regionsEg ethanol, glycerol, propylene gycol
• What's the purpose of using cosolvents?

  - to get aq systems where drug solubility is higher than aq solubility- to form increased [drug]- to improve stability of formulation (thermodynamically)

  
• What effect does increasing cosolvents have on solubility?

  increasing cosolvents exponentially increases solubilty

  
• What does the solubilisation slope (gradient) show?What happens to the gradient when you decrease the polarity of a solvent?

  The effectiveness of a cosolvent as a solubiliser for a particular solutegradient increases with decreasing polarity

  
• What's the equation for working out solubilisation by cosolvency?(in form y=mx+c/y=c+mx?)

  logSmixture = logSwater + σ Fcwhere Smixture = solubility of mixtureSwater = solubility of drug in just waterσ = gradientFc = volume fraction of cosolvent

  
• What effect do cosolvents have on a) nonpolar/semipolar solutes and b) polar solutes in water?

  A) cosolvent addition increases solubility of nonpolar/semipolar solutes in water- as solute polarity increases, cosolvent efficiency decreasesB) cosolvents decrease solubility of polar solutes in water
• What happens to polarity as log P increases?

  As log P increases, polarity decreases