L20 - Drug Solubility and Dissolution Rate 5

• Define surfactants

  Surface active agents used to enhance solubility of drugs in water by micellisation

  
• How are surfactants classified?

  Based on the charge carried by their polar part: anionic, cationic, non-ionic, and zwitterionic
• Eg what's the classification of sodium stearate?

  Anionic - bc counter ion (Na+) is +ve
• Eg what's the classification of dodecylpyridinium chloride?

  Cationic - bc counter ion (Cl-) is -ve
• What's the classification of Macrogol/Lauromacrogol/Cetomacrogol?

  Non-ionic
• Anionic surfactants(What are they used for? Are they toxic?)

  Anionic surfactants are widely used and inexpensive, but they can be toxic for external applications. They are mainly used as oil-in-water (O/W) emulsifiers
• Cationic surfactants(What are they used for? Are they toxic?)


  - disinfectant and preservative properties. - O/W emulsifiers- can be toxic
• Non-ionic surfactants(What are they used for? Are they toxic? How does their polarity compare?)


  - O/W and W/O emulsifiers.- Low toxicity and irritancy; suitable for oral and parenteral use- OH and COC (hydroxyl and ether) groups important- less polar than ionised groups, so need more units, eg POE (polyoxyethylene) chains - larger polar region than ionic

  
• POE number


  no. of monomeric POE groups in a unit
• Define moiety


  a portion or part of something
• What are emulsifiers?What do they do?

  surfactants used to decrease surface tension betwen Oil and Water by helping polar/non-polar emulsions mix
• What is the hydrophobic portion of a surface active drug?(Examples?)

  - long alkyl chains or - aromatic/herterocyclic ringsEg penicillin G, chlorpromazine (tranquiliser), imipramine (antidepressant), diphenhydramine
• How do surfactants solubilise drugs?

  - add drugs to water at same time as micellisation (driven by the hydrophobic effect)- drugs engulfed in micelle

  
• Define SolubilisationWhat's plotted on solubilisation graph?

  Where water-insoluble substances into aqueous solution by incorporating them into micellessolubility (y) against % surfactant (x)

  
• Where does solubilisation occur?

  - depends on chemical nature of solubilisate (drug)- the more polar the solute, the more likely to be solubilised close to the surface

  
• How do you choose which surfactant is best to solubilise a drug?- what parameter do we use?- What do we need to consider?

  use k (kappa) - quantifies micelle solubilisation.The higher k, the more moles it can solubilise.Consider:- amount of surfactant that can be placed in water: longer chains = lower solubility- ability to solubilise a solute (ie get drug molecule in middle). Shorter chains = higher CMC, requiring MORE [ surfactant]

  
• Define Molar Solubilisation Capacity (aka ratio/efficiency)What does it do?


  no. of moles of solute that can be solubilised by 1 mole of micellar surfactantMeasures the ability of a surfactant to solubilise a soluteIf you have k, you can find total solubility of a drug

  
• What's the eqn for Molar Solubilisation Capacity (k)?

  k = Sm / CmicORk = Stotal - Swater / [surfactant] - CMCwhere Sm = molar solubility of solute in the micelleCmic = molar conc of micellar surfactantsS = solubility (in total/in water)

  
• Solubilisation Capacity Plot- what do you plot? - What units must these both have?- how do you find k (molar solubilisation capacity?)

  y = [solute]x = [surfactant] Both must be in MOLAR. k = gradient

  
• What's the eqn for total solubility of a drug?

  Stotal = Swater + k (Csurfactant - CMC)

  
• Why is solubilising a polar/semipolar drug difficult?

  Can't change size of polar head of micelle. Most ionic surfactants have same size polar head, so don't increase solubility too greatlyLikewise, can't increase size of palisade layer between polar and non-polar regions of micelle for semipolar drugs
• How to solubilise a non-polar drug?

  - use surfactant with long non-polar tail (alkyl chain), as its core will be large BUT balance this with solubility - longer chains have lower solubilities!
• What happens to CMC as alkyl chain length increases? Solubility? Surface Activity? Surface tension?

  CMC decreases, so solubility decreases.so Surface activity increasesThe longer the chain, the greater surfactant tendency to adsorb at surface
• What's the optimum carbon chain length for surfactants?

  12-16 carbons bc:- gives low CMC and doesn't compromise solubility
• What's Lundelius' Rule?

  any factor that decreases surfactant solubility promotes surface activity
• HLB scaleWhat is it? What does a lower/higher HLB mean?What values are given to 100% hydrophilic or lipophilic?

  Hydrophilic-Lipophilic Balance ScaleLower = more Lipophilic (non-polar)Higher = more Hydrophilic (polar)100% lipophilic: HLB = 1100% hydrophilic: HLB = 20
• How to calculate HLB of a mixture of surfactants? What's the eqn?

  As a weighted average of the individual HLB valuesHLBmix = x HLBa + (1-x) HLBbwherex = fraction of surfactant a/b*use decimals for fractions

  
• Define Required HLBHow can we find it?

  The HLB value of a surfactant needed to form a stable emulsion with a specific oil phase.Rearrange HLBmix = x HLBa + (1-x)HLBb
• Define emulgent/emulsifiers

  surfactants that stabilise emulsions
• Phase Inversion Temperature (PIT)What happens to hydrophilic/lipophilic nature at PIT?


  Temp at which an emulsifier changes from an O/W to W/Ohydrophilic and lipophilic nature balance
• Why does HLB of an emulsifier vary with temp?Why is this more pronouced with non-ionic surfactants? Why might an emulsifier be less soluble in water at higher temps?


  Because relative solubilitites of lipo/hydrophilic parts of emulsifier vary with tempBc non-ionic surfactant solubility depends on hydrogen bonding: increasing temp weakens H bonds, so emulsifier may be less soluble in water.