L19 - Drug Solubility and Dissolution Rate 4

• Inclusion Compounds (what are they? example? what effect do they have on solubility?)

  Result from incorporation of non-polar portion of one molecule into non-polar cavity of another that is water solubleEg cyclodextrin- increase solubility

  
• What effect do cosolvents have on polarity of water?

  Cosolvents decrease polarity of water
• What are Cyclodextrinsstructure? what are they used for?

  Enzymatically modified starches that form inclusion compounds. Cylindrical ring:- Hydrophilic outer ring (soluble in water) - non-polar internal cavity - lipophilic molecules can be added into complex cavity - drug delivery system to increase solubility

  
• What is meant by inclusion complex?What do they form?

  Incorporates the cyclodextrin ring, and hydrophobic drug as a total drug delivery system.Form crystalline complexes
• Host-Guest Ratio


  The ratio of the complexing agent (host) to the solute (guest) in an inclusion compound.
• Crystalline Complexes(what are they? what do they result in?)

  Complexes formed between cyclodextrins and poorly soluble drugs, resulting in improved solubility and dissolution rate.
• Eg: How is solubility of ibuprofen improved?

  Beta-cyclodextrin and ibuprofen complex formed when both put in water bath- increased solubility and dissolution rate of ibuprofen
• Cyclodextrin adverse effects eg:

  Beta-CD has high affinity for cholesterol and is haemolytic ( destroys erythrocytes)

  
• Define Surfactants(what do they do? where are the mainly used?)

  Surface Active Agents:Amphipathic molecules eg SLS/bile/washing up liquid-Reduce the surface tension at an interface between two imiscible liquids, eg water and oil.- mainly used in emulsions, eg o/w, w/o
• What's the structure of a surfactant?(what do the balance of these regions determine?)

  - hydrophilic, polar head group (can be ionic/non-ionic)- lipophilic, non-polar chainBalance determines:- surfactant solubility in water and oil- applicationsplace on HLB scale

  
• Criteria for a good polar region (hydrophilic head)

  - high affinity for water- must be able to pull long hydrocarbon tails into water- must be sufficiently polar to hold the nonpolar region of the surfactant in solution

  
• How do you choose the best surfactant?

  - look at the difference in polarity of head and tail- the larger the difference, the better the surfactant.
• Define Surface Tension

  The force that acts on the surface of a liquid and minimises its area.
• What happens if two phases are not compatible at their surface?

  Molecules don't want to mix so they retract. Tension makes system thermodynamically unstable
• Define Surface Activity


  - the ability to reduce surface tension at an interface without requiring large concentrations- the lower the required conc, the better the surface active properties of a solute
• Amphiphiles


  Molecules that have both hydrophilic (polar) and hydrophobic (nonpolar) regions.
• What causes the highest reduction in interfacial tension?


  Using solutes that have:- one element w/ high affinity for solvent- one element w/ low affinity for solventthis allows mixing of two phases together
• What is the HLB scale?

  Hydrophilic-Lipophilic BalanceTells us efficacy of surfactants

  
• How can we classify surfactants?

  By the charge of the polar region:- anionic- cationic- zwitterionic- non-ionic
• Micelles


  Aggregates of surfactant molecules that form in concentrated solutions above the critical micelle concentration (CMC).Colloidal
• Aggregation number


  number of monomers that aggregate to form a micelle
• Critical Micelle Concentration (CMC)


  The concentration of surfactant at which micelles start to form.
• What factors increase CMC?

  - increase in polarity of head group
• What factors decrease CMC?

  - increasing carbon chain length- temp- pH- a 2nd surfactant- addition of electrolytes

  
• Micellisation(what happens?)

  - surfactants self-aggregate at higher concentrations- alternative mechanism to adsorption- water molecules around non-polar tail retract, making system more thermodynamically unstable- First, adsorption occurs - surfactants adhere at the surface of water

  
• Define Adsorption

  A way to stabilise systemIf too much surfactant is added, the system becomes unstable so molecules try to escape by adhering to the surface

  
• What happens when surfactants have long alkyl tails?

  The longer the alkyl tails, the more thermodynamically unstable, so the lower the CMC.Molecules self-aggregate at lower concShort alkyl chains have a higher CMC - need more molecules to make it thermodynamically unstable
• What surfactant properties change at CMC?

  - osmotic pressure (increases up to CMC, then stabilises)- turbidity (increases)- electrical conductance (decreases)- surface tension (decreases)

  
• Hydrophobic Effect


  The tendency of hydrophobic regions of molecules to minimize contact with water, driving the formation of micelles.
• Osmotic Pressure


  The pressure required to prevent the flow of solvent across a semipermeable membrane due to differences in solute concentration.
• Turbidity(what effect does increasing [surfactant] have on turbidity?)

  The cloudiness of a liquid caused by the presence of suspended particles.Increasing [surfactant] increases turbidity
• Electrical Conductance(what happens to it after CMC?)

  The ability of a solution to conduct electricity, influenced by the presence of ions in solution.Decreases after CMC
• Colloidal Systems


  Systems in which particles are dispersed in a continuous medium, Eg micelles in a surfactant solution.
• Define Kraft Point

  The temperature at which CMC = solubility of surfactant

  
• What happens at temps higher/lower than the Kraft point?

  T< Kraft point:- CMC>solubility so micelles can't formT>Kraft point:- micelle formation (self-solubilisation)- unassociated surfactants have limited solubilities- micelles are highly soluble and can accommodate a large amount of surfactant

  
• Define Cloud Point(how is it reached?)

  The temperature at which a non-ionic surfactant solution becomes cloudy after temp increase due to the formation of large micelles.1) Dehydration of POE (polyethylene) chains2) decreased water solubility3) large micelle formation, hence turbidity increasesReversible on cooling!
• Critical Micelle pH

  pH changes leads to micellisation if:- ionised form of compound is surface active (decreases surface tension)- UNionised form is surface INactive (lower CMC than ionised form)

  
• Geometric Properties of Micelles(what happens at high [surfactant]?)

  at higher [surfactant], higher viscosity may occur:- cylindrical rods, flattened disks- liquid crystals (hexagonal phase, middle phase)- lamellar phase- bilayers- vesicles