L5/L6 - Thermodynamics

• Why is thermodynamics important in pharmaceuticals?

  - Partitioning of drugs (e.g. between membranes and aqueous fluids)- Drug solubility and diffusion- Micellization of surfactants- Drug-receptor interactions/ protein binding- Phase transitions
• First law of thermodynamics


  Conservation of energy - energy cannot be created or destroyed, only transferred
• Second law of thermodynamics

  Entropy will always increase over time
• Third law of thermodynamics

  Entropy of a perfect crystal at 0k is 0 (due to greatest possible orderliness. Entropy of a system approaches a constant value as the temperature approaches absolute zero
• Internal Energy (U) (What is it? How can it be changed? What's the equation?)

  Sum of all kinetic and potential energies. Can be changed by transferring energy as work (w) or heat (q).In Thermodynamics, we're interested in changes to U, not the absolute value△U = w + q
• Enthalpy (What is it? What's the equation? What's the equation linking enthalpy and internal energy (U)?)

  Heat change at a constant pressure. q = m c △t. U = H + PV(where U = internal energy, H = enthalp, P = pressure and V = volume)
• Entropy(What is it? When does it change?)

  A measure of disorder in a system (S).Changes with phase transitions (gases > liquid > solid)There is no disorder at absolute zero
• Gibbs Free Energy(What's the equation? What's the requirement for a reaction to be feasible? What happens to ΔG in a spontaneous process?)

  ΔG = ΔH - TΔS- Must be less than 0 for reaction to be feasible- ΔG decreases in a spontaneous process until system reaches equilibrium

  
• What's the equation for standard free energy change?What's the Van't Hoff equation?What graph do we plot to show this? What's the gradient?

  ΔG = RT lnK. ln K = - (ΔH⦵/RT) + constant. lnk vs 1/T. The gradient is ΔH

  
• Partition Coefficient (k) (What is k? What are the equations including oil, water and solubility? What does it show at equilibrium?)

  K = C oil / C waterk = drug's relative affinity for oil compared to waterK = S oil/S waterC oil / S oil = C water / S waterAt equilibrium, the degree of saturation of the drug in two phases is identical. The drug's chemical potential in oil and water is the same.
• The drug's Leaving Tendency(What is it? When is it maximised? Eg transdermal patches)

  The degree of saturation (C oil / S oil = C water / S water)Maximised (and equal to 1) when C oil = S oil OR Cwater = Swater(For drug absorption across a membrane, the close the concentration to Sformulation, the faster delivery rate. EG Transdermal patches - drug is present at concentrations close to it's solubility in adhesive layer, so delivered at maximum flux)
• Fick's First Law(What is it? What is flux? What happends to free energy with changes in entropy?

  The flux (flow) at any point in the system is proportional to the potential energy gradient. Force- Flux relationshipFree energy is minimised when entropy is maximised
• Thermodynamics of protein binding(What does -ve ΔG, ΔH and +ve ΔS mean?

  -ve ΔG = binding is spontaneous-ve ΔH = exothermic +ve ΔS = loss of structured water on binding (contributes to -ve ΔG)
• Critical Micelle Concentration(What is it? What happens with increasing polarity/hydrocarbon chain length?)

  The concentration at which micellisation occurs spontaneouslyCMC decreases with increasing hydrocarbon chain lengthCMC increases as head group becomes more polar
• Surfactant (eg SLS)What is a surfactant?

  Surface Active Agent (with polar, hydrophilic heads and non-polar hydrophobic tails)
• Hydrophobic Effect


  Surfactants populate the surface of water until it is full, then they form micelles beneath the surface