L16 - Drug Solubility and Dissolution Rate 1

• Drug


  A substance used to treat, cure, or prevent a disease or medical condition.
• Dosage form


  The physical form in which a drug is administered
• Solubility(what is it? how does a decrease affect bioavailability? how is it measured? what happens to anything more than solubility value?)

  The ability of a substance to dissolve in a solvent.Decreased solubility decreases bioavailabilityCompounds need to be dissolved to be absorbed via orla route.max. mass/volume of a solute dissolved in a given mass/volume of solute at given temp.anything more than sol. value will precipitate

  
• Weak acidic/basic drug solubility(how can this change in the GI tract?)

  - changes as pH changes- ionise at dif pHs- acidic drugs ionise at high pHs, basic drugs ionise at low pHs
• Which dosage form is the most bioavailable?(compare this with suspensions and tablets)

  - Aqueous solution, as doesn't have to undergo dissolution step- suspensions have lower aq sol, bust still comparable- tablets have to be dissolved which takes time, so lower bioavailability
• Solution


  molecular dispersion of 2+ components which form a homogeneous (1 phase) system
• miscibility


  the ability of a liquid to completely dissolve in another liquid
• Solvent


  component determining phase of solution
• Solutes


  are dissolved in the solvent. Dispersed as molecules/ions
• Saturated solution

  solute in equilibrium with solid phase
• Dissolution rate


  The rate at which a drug dissolves in a solvent.Change in mass of drug over time
• BCS - Biopharmaceutical Classification System (BCS)(how does it classify drugs? How many classes? What does it help predict?)


  Classification of drugs according to their solubility and permeability across the GI mucosa. Helps predict bioavailability and design in vitro dissolution tests.

  
• class I

  high solubility, high permeability(eg propranolol, metoprolol)
• class II

  low solubility, high permeability
• class III

  high solubility, low permeability
• class IV

  low solubility, low permeability(eg taxol)
• Bioavailability (BA)


  The extent and rate at which a drug is absorbed into the systemic circulation and becomes available at the site of action.
• Supersaturated solution


  A solution that contains more solute than it would normally hold at a given temperature.Fails to crystallise on cooling
• Unsaturated or subsaturated solution


  A solution in which the concentration of the dissolved solute is below the saturation point at a given temperature.
• Dissolution


  The process by which a solid drug particle dissolves in a fluid.
• Dissolution rate


  The rate at which a drug particle dissolves in a fluid.

  
• Diffusion layer


  Saturated solution surrounding drug particle, where drug molecules dissolve and diffuse into the bulk solution.

  
• Fick's First Law(what does it state? what's the eqn?)

  substances diffuse from high conc to low concJ = DKA ΔC / hJ = fluxD = diffusion coefficientK = partition coefficientA = particle SAΔC = Cs - Cbulk (moldm-3)h = membrane thickness

  
• Noyes-Whitney equation


  Describes the dissolution rate of a drug and factors that affect it.dissolution rate = k A (Cs - C)

  
• How can we increase dissolution rate?

  - increase particle SA by reducing particle size- decrease thickness of membrane- increase drug solubility in diffusion layer- increase k (dissolution rate constant) as incorporates drug diffusion coefficient and diffusion layer thickness.

  
• Dissolution Rate Constant(what is it? what's the eqn?)

  A constant in the Noyes-Whitney equation that represents the rate of dissolution and is influenced by factors like drug diffusion coefficient and boundary layer thickness.k = D/Vhk = dissolution constantD = diffusion coefficient of solute/solventV = vol of dissolution mediumh = membrane thickness
• Polymorphism


  The ability of a substance to exist in different crystal forms, which can affect its solubility and dissolution rate.