PHYS 1107 Lecture Notes - Lecture 4: Chemotherapy, Cholesterol, Heme
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" dL!=!decilitre!=!100mL!
" If!a!mixture!is!made!up!of!water!and!drug,!add!x!grams!of!drug,!and!then!(100!–!x)!mL!of!water!to!
make!the!mixture!a!total!amount!of!100mL!(or!100g)!
o I.e.!add!water!to!make!the!volume!up!to!100mL!!
" Dilution!≈!paediatric!sample!–!use!C1V1=C2V2!
" If!working!with!a!liquid!drug!or!solvent!other!than!water!(e.g.!ethanol)!–!density!formula!!
!
748349-(/69(:*53+4*6-(
:*53+4*6(
Mixture!of!two!or!more!components!that!form!a!single!phase!which!is!homogeneous!
down!to!the!molecular!level!
!./-,(
Part!of!a!system!separated!by!one!or!more!boundaries/interfaces,!which!can!be!
separated!physically!(e.g.!filtration,!centrifuge)!
;4--*53+4*6(
Transfer!of!molecules!or!ions!from!the!solid!state!into!solution!
<4-24=454+>(
Combination!of!two!solvents!that!mix!completely!to!form!a!homogenous!solution!
!
Solubility!
" Limit!to!which!a!solute!can!be!dissolved!in!a!solvent!under!a!particular!set!of!conditions!
" Determined!at!20°C!
" Based!on!amount!of!solvent!in!mL!or!grams!(“parts”),!required!to!dissolve!1g!of!drug/excipient!
o Soluble!–!10"30!parts!solvent!
o Insoluble!–!>10000!parts!solvent(!
" Water!solubility!–!depends!on!polarity!and!functional!groups!–!H"bonds!and!ion"dipole!bonds!!
o "NH,!"OH!or!C=O!functional!groups!will!H"bond!with!water!
o Ion"dipole!bonds!are!even!stronger!than!hydrogen!bonds!
!
Salt!form!of!drugs!
" Salt!form!of!drugs!are!more!water!soluble!than!neutral!form!
" They!form!more,!and!stronger,!hydrogen!bonds!with!water!
" However:!
o Samples!can!be!hygroscopic!(draw!in!moisture!from!air)!
o Can!change!pH!of!solution!(important!for!injection!and!oral!solutions)!
o Reactions!with!packaging!(glass!and!basic!solutions)!
o Different!salts!of!a!drug!can!work!differently!
o Salts!interact!with!each!other!and!precipitate!out!of!solution!!
" Most!common!salt!forms!of!drugs:!
o Acidic!drugs!–!Na+,!K+,!Ca2+,!Zn2+!
o Basic!drugs!–!Cl",!SO4
2",!PO4
3"!
!
Salting!out!
" Precipitation!of!peptides!and!proteins!from!solution!at!high!salt!concentrations!
" At!high![salt],!water!molecules!bind!to!the!salt!instead!of!the!protein!(not!enough!free!water!
available)!–!causes!precipitation!of!protein!molecules!(less!soluble!solute)!
" Some!drugs!based!on!proteins!and!peptides!–!must!ensure!drugs!do!not!precipitate!
(
;03?@14A+30,(
w/w!
grams/100g!
w/v!
grams/100mL!
v/v!
mL/100mL!
v/w!
mL/100g!
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" Van!der!Waals!radius!–!imaginary!radius!of!an!atom!or!molecule!!
o Physical!space!the!drug/particle!takes!up!
" Hydrodynamic!radius!–!imaginary!radius!of!drug/particle!and!any!bound!
subparticles!(e.g.!water)!that!travel!through!the!solution!with!the!drug!particle!
" Brownian!motion!–!random!movement!of!particles!suspended!in!a!liquid!or!gas!
o Caused!by!collisions!with!molecules!of!the!surrounding!medium!
o Rate!of!drug/particle!movement!through!solution!is!directly!related!to!size!
(
Stokes!–!Einstein!equation!
" Rate!at!which!drug!diffuses!through!solution!is!largely!dependent!on!hydrodynamic!radius!and!
solvent!viscosity!
" !=!"
!!"#!!
o D!=!diffusion!coefficient!(m2s"1)!
o K!=!Boltzmann!constant!(1.38*10"23JK"1)!
o T!=!temperature!(K)!
o η!=!solvent!viscosity!(water:!1.232*10"3Pa!S)!
o r!=!hydrodynamic!radius!(metres)!
!
B/C*30(C0,--30,(
" Pressure!of!vapour!above!liquid!when!liquid!and!vapour!are!at!equilibrium!
" Amount!of!vapour!about!liquid!depends!on!intermolecular!forces!
o More!bonding!between!molecules!–!less!vapour!formed!–!lower!vapour!pressure!
" Lower!vapour!pressure!–!boils!at!higher!temperature!
" Higher!vapour!pressure!–!boils!at!lower!temperature!
" 50/50!mixture!of!ethanol!and!water!
o Does!NOT!mean!mixture!of!vapour!is!also!50/50!
o More!ethanol!molecules!in!air!than!water!since!
ethanol!has!a!higher!vapour!pressure!
" !
!"!#$ =!!!
!+!!!
!!
o Ptotal!=!total!pressure!from!all!molecules!in!the!gas/vapour!phase!
o XA!=!mole!fraction!of!gas!A!
! Total!of!mole!fractions!(XA!+!XB)!must!equal!1!
o PA!=!vapour!pressure!of!gas!A!
o Raoult’s!Law!
!
'(C*5/0(1*5,235,-(
%(C*5/0(%(6*6DC*5/0(
'(6*6DC*5/0(
H"bonding!–!keeps!in!liquid!phase!
Repulsion!–!more!molecules!in!
gas/vapour!phase!
Ideal!conditions!
Hydrophobic!forces!very!weak;!
no!repulsion!
Lower!vapour!pressure!for!both!
Higher!BP!
Higher!VP!
Lower!BP!
No!effect!on!partial!pressures!of!
the!gases/vapours!
!
!
!
!
E0,,F46?(C*46+(9,C0,--4*6(
" Dissolution!of!polar!solute!into!a!solvent!results!in!drop!in!the!freezing!point!of!the!solvent!
o Salt!+!water!–!lowers!freezing!point,!so!water!doesn’t!freeze!as!easily!
o Blood!contains!many!polar!molecules!(proteins,!salts)!–!lowers!freezing!point!of!blood!
" Size!of!FPD!depends!on!solvent!and!amount!of!solute!(no.!molecules,!not!no.!moles)!
" Any!solution!injected!into!vein,!or!eye!drops!–!must!have!FDP!of!0.52°C!
G./6?,(
$/+,(*H(903?(
94HH3-4*6!
Increase!temperature!
Faster!
Change!form!water!to!oil!
Slower!
Change!from!neutral!
drug!to!salt!form!
Slower!
Make!a!nanoparticle!
formulation!of!the!drug!
Slower!
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!.>-42/5(H/2+*0-(/HH,2+46?(-*53=454+>(
How!drugs!dissolve!
" High!concentration!of!drug!in!the!‘diffusion!layer’!(area!close!to!the!drug!particle)!
o However,!drug!molecules!in!solution!⇌!drug!molecules!back!to!drug!particle!
" Only!drug!molecules!at!the!solid!particle!surface!can!dissociate!and!dissolve!!
o Drugs!dissolve!into!bulk!solution!
!
Factors!affecting!solubility!
" Size!of!the!particles!
o Smaller!particles!have!higher!SA:V!than!larger!particles!!
" Dispersibility!of!the!solid!particles!–!e.g.!if!they!stick!to!each!other!
" Porosity!of!the!particles!
o Holes!within!structure!allows!water!access!to!inner!parts!of!the!particles!
" Crystalline!or!amorphous!or!a!mixture!of!both!
#1*0C.*3-(
G0>-+/5546,(
No!organised!structure!
Organised!structure!
Generally!more!soluble!
(less!bonds!to!break)!
Both!polar!and!non"polar!bonds!are!present!
!
Crystal!type!I!
!
Crystal!type!II!
!
!
Polymorphism!
" Bonds!between!drug!molecules!in!the!solid!state!must!be!broken!to!dissolve!
o Amorphous!drugs!almost!always!more!soluble!than!crystalline!
" However,!all!systems!try!to!move!to!the!lowest!energy!state!
o Over!time,!amorphous!drugs!can!become!crystalline!
o Crystalline!drugs!can!change!into!another!form!of!crystalline!
" Polymorphism!–!where!there!exists!more!than!one!crystalline!state!for!a!drug!
o Paracetamol!–!metastable!polymorph!II!dissolves!faster!in!water!and!is!used!for!tablets!
! Heating!converts!into!less!desirable!polymorph!I!
o Ritonavir!–!plate"like!crystal!is!preferable!over!needle"like!crystal!
! Needle"like!form!was!very!stable!(didn’t!change!form)!but!less!soluble!!
!
Solid!drug!production!!
" Methods!–!spray!drying,!freeze!drying,!evaporation,!precipitation!
o Involves!removal!of!solvent!
o Produces!amorphous!material!–!fast!drying!–!no!time!to!form!crystalline!bonds!
" Solvates!and!hydrates!–!solvent!trapped!in!solid!drug!particles!
o Less!soluble!than!anhydrous!solid!particles!
! Drugs!are!already!bonded!to!solvent!molecules!(
(
G.,142/5(I46,+42-(
" Used!to!determine:!
o How!fast!a!drug!is!metabolised!or!excreted!
o How!long!radioisotopes!will!emit!radiation!within!the!body!
o Shelf"life!of!drugs!based!on!their!rate!of!degradation!
o How!long!after!one!drug!is!administered!you!have!to!wait!before!next!drug!can!be!given!
o Drug!release!from!controlled!or!modified!release!formulations!and!patches!
" For!chemical!kinetics,!only!non"reversible!reactions!will!be!considered!
!
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