Physical Pharmaceutics and Formulation A - Lecture notes - 1822 notes PDF

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PHAR1822(Notes( Pharmaceutical(calculations( 𝑚 𝑚𝑎𝑠𝑠!(𝑔) ( Drug/mixture( 𝑑= ! 𝑑𝑒𝑛𝑠𝑖𝑡𝑦!(𝑔/𝑚𝐿) = ! ! 𝑣 w/w! grams/100g! 𝑣𝑜𝑙𝑢𝑚𝑒!(𝑚𝐿) 𝑛 𝑚𝑜𝑙𝑒𝑠!(𝑚𝑜𝑙) w/v! grams/100mL! 𝑐= ! 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛!(𝑚𝑜𝑙 𝐿) ! = ! 𝑣 v/v! mL/100mL! 𝑣𝑜𝑙𝑢𝑚𝑒!(𝐿) 𝑚 𝑚𝑎𝑠𝑠!(𝑔) v/w! mL/100g! ! 𝑛= ! 𝑛𝑜. 𝑚𝑜𝑙𝑒𝑠 = ! 𝑀𝑀 𝑚𝑜𝑙𝑒𝑐𝑢𝑙𝑎𝑟!𝑚𝑎𝑠𝑠!(𝑔 𝑚𝑜𝑙) 𝑐! 𝑣! = 𝑐! 𝑣! ! 𝑢𝑠𝑒!𝑓𝑜𝑟!𝑑𝑖𝑙𝑢𝑡𝑖𝑜𝑛𝑠! ! " 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!! ! Liquids(and(Solutions( Mixture!of!two!or!more!components!that!form!a!single!phase!which!is!homogeneous! Solution( down!to!the!molecular!level! Part!of!a!system!separated!by!one!or!more!boundaries/interfaces,!which!can!be! Phase( separated!physically!(e.g.!filtration,!centrifuge)! Transfer!of!molecules!or!ions!from!the!solid!state!into!solution! Dissolution( Combination!of!two!solvents!that!mix!completely!to!form!a!homogenous!solution! Miscibility( ! 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!

" " "

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! Change( Rate(of(drug( !" " 𝐷 = !!"#!! diffusion! o D!=!diffusion!coefficient!(m2s"1)! Increase!temperature! Faster! o K!=!Boltzmann!constant!(1.38*10"23JK"1)! Change!form!water!to!oil! Slower! o T!=!temperature!(K)! Change!from!neutral! Slower! o η!=!solvent!viscosity!(water:!1.232*10"3Pa!S)! drug!to!salt!form! o r!=!hydrodynamic!radius!(metres)! Make!a!nanoparticle! Slower! ! formulation!of!the!drug! Vapour(pressure( " 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! " 𝑃!"!#$ = 𝑋! 𝑃! + 𝑋! 𝑃! ! 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! ! 2(polar(molecules( 1(polar(1(nonDpolar( 2(nonDpolar( H"bonding!–!keeps!in!liquid!phase! Repulsion!–!more!molecules!in! Ideal!conditions! gas/vapour!phase! Hydrophobic!forces!very!weak;! no!repulsion! Lower!vapour!pressure!for!both! Higher!VP! No!effect!on!partial!pressures!of! Higher!BP! Lower!BP! the!gases/vapours!

!

!

!

! Freezing(point(depression( " 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!

Physical(factors(affecting(solubility( 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! Amorphous( Crystalline( No!organised!structure! Organised!structure! Generally!more!soluble! Both!polar!and!non"polar!bonds!are!present! (less!bonds!to!break)! 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!( ( Chemical(Kinetics( " 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! !

Rate!of!reaction! " How!fast!reactants!are!consumed!or!how!fast!products!are!formed! " R!(rate!of!reaction)!=!∆products!÷ ∆time!=!−∆reactants!÷ ∆time! " R!=![P2]!–![P1]!/!t2!–!t1! " Determined!by:! o Order!of!reaction! o Temperature! o Activation!energy! o Whether!a!catalyst!is!used! ! ! ! ! ! ! ! ! ! ! ! Reaction!orders! ( ZeroD order( reactions( FirstD order( reactions( SecondD order( reactions(

( " "

"

Definition( R!not&affected!by!conc.!of! reactants!or!products! ! R!depends!on![one! reactant]1!! ! Type!1:!Only!one!reactant! (A!→!B)! ! Type!2:!Two!reactants! (A+B!→!C!or!A+B!→!C+D)! !

Reaction(rate((R)( 𝑅 = !𝑘!

Equation( 𝐴 = 𝐴 ! − 𝑘𝑡! !

𝑅 = 𝑘[𝐴]! ! !

"1 [!] ln [!] = −𝑘𝑡!or! 𝐴 = [𝐴]! 𝑒 !!" ! Time !

𝑅 = 𝑘[𝐴]! ! !

1 1 = + 𝑘𝑡! [𝐴] [𝐴]!

𝑅 = 𝑘[𝐴][𝐵]! !

1 [𝐵][𝐴]! = 𝑘𝑡! ln [𝐵]! − [𝐴]! [𝐴][𝐵]!

!

!

Conc."1!×! time"1!

For!reaction!A+B!→!C+D,!R!=!k![A]x![B]y! Pseudo"first!order!reactions! o Some!reactions!that!would!normally!be!higher!order!reactions!can!be!considered!pseudo! first"order!reactions! o E.g.!aspirin!+!water!→!salicylic!acid!+!acetic!acid! §฀ R!=!k![aspirin]![water]! §฀ But!in!the!human!body,![water]!is!essentially!constant!and!so!can!be!removed! from!the!equation,!making!R!=!k![aspirin]! Example!of!type!2!second"order!reaction!! o Renaturation!of!DNA!in!solution!–!DNA!fragments!are!heated!and!denature!into!single! strands!(A!and!B).!As!the!solution!cools,!the!single!strands!recombine!(renature)!to!form! double"stranded!fragments!

! [A0]! [A]! K! t!

Units(of(k( Conc.!×! time"1!

Starting!concentration!of!reactant! Concentration!of!a!reactant!after!time!(t)! Rate!constant! Time!!

Activation!energy!(Ea)! " Activation!energy!–!minimum!amount!of!energy!required!to!initiate!a!chemical!reaction! " Linear!relationship!between!temperature!and!reaction!rate! !!

!

"

o ln 𝑘 = ln 𝐴 − ! !or!𝑘 = 𝐴𝑒 !!"! !" o T!=!absolute!temperature!(K)!! o R!=!gas!constant! Determining!activation!energy! o

!!

ln ! =

!! ! !

!

(! − !!)!

! ! ! ! ! ! ! ! ! Half"life!(t1/2)! " Half"life!of!a!reaction!–!time!taken!for!the!concentration!of!the!reactant!to!decrease!by!half!of!its! original!value! " Only!applicable!to!first!and!second!order!reactions! "

!" !

!.!"#

Half"life!equation:!𝑡!/! = = ! ! ! o I.e.!to!calculate!the!half"life,!only!the!rate!constant!is!required! o Deriving!the!equation:!! [!] §฀ First"order!reactions:!ln[!] = −𝑘𝑡! !

§฀

Where![A0]!is!the!initial!concentration,![A]!is!half!the!original!concentration!

§฀

Hence,!ln!"" = ln 0.5 = −𝑘𝑡!

!"

! Osmosis( " Reverse!osmosis!–!produce!clean!drinking!water!from!seawater!(using!force)! " Osmotic!pressure!–!amount!of!external!pressure!applied!to!a!solution!to!prevent!it!being!diluted!by! the!entry!of!solvent!via!osmosis!! o No!net!movement!of!water!across!membrane!=!solutions!are!at!equal!osmotic!pressure!=! iso"osmotic!=!equilibrium! " Blood!cells!and!serum!–!osmotic!system! o Dissolved!components!–!salts,!proteins!and!drugs!contribute!to!osmotic!pressure! o Normal!blood!serum!concentration!is!308mOsM!(milliosmolar)! " Osmole!–!total!number!of!dissolved!components!in!a!solution!! " Hypertonic!–!concentration!of!blood!serum!>!of!RBC! o Cells!pump!water!out!into!blood!serum! o Shrinks!RBC!(repairable)! " Hypotonic!–!concentration!in!blood!serum!!monovalent!! Add(surfactants( " Make!insoluble!particles!mix!with!liquid!phase! " Ionic!–!cause!flocculation!or!de"flocculation!depending!on!particle!charge! o If!particle!opposite!charge!to!surfactant,!neutralisation!results!in! flocculation! " Linear,!branched!chain!molecules!form!gel"like!networks!within!aqueous! Add(polymers( E.g.!starch,!silicates! phase!and!adsorb!to!the!dispersed!molecules!–!increase!flocculation! ! Measurement!of!suspension!behaviour! " F!=!Vu/Vo! o F!=!sedimentation!volume! o Vu!=!ultimate!volume!of!the!sediment! o Vo!=!original!volume!of!the!suspension! " In!flocculate!suspensions,!flocs!tend!to!fall!together!–!produces!distinct!boundary!between!the! sediment!and!supernatant!liquid! " In!deflocculated!suspensions,!no!clear!boundary!formed,!supernatant!stays!turbid!for!much!longer! " Sedimentation!volume!just!gives!the!qualitative!account!of!flocculation!–!normally,!F!74%!of!total!volume!–!leads!to!phase!inversion!and!cracking! " Oil!in!water!emulsion!(o/w)!(e.g.!milk)! o Easier!to!prepare!–!oil!is!relatively!easy!to!disperse!in!aqueous!continuous!phase! o Solubility!in!oil!phase! o Topical!–!washable,!more!cosmetically!acceptable!than!w/o!emulsions! o Oral!–!feel,!aqueous!volume!and!taste!masking! o IV!injections!are!o/w! " Water!in!oil!emulsion!(w/o)! o Topical!–!oil!base!makes!emulsion!feel!greasy,!hydrating!effect,!cleaning!effect! o Injectables!–!generally!only!depot! " Cohesive!force!between!the!molecules!of!each!separate!liquid!>!adhesive!force!! o Thus,!the!two!immiscible!liquids!fail!to!remain!mixed! " Identifying!emulsion!type!–!measure!conductivity,!dye!tests!(phenol!red),!miscibility!test!with!water!! ! Emulsion!formation! " Two!competing!processes! 1. Disruption!of!the!interphase!between!bulk!and!immiscible!phases! 2. Stabilisation!of!the!dispersed!phase!once!formed!–!emulsifying!agents!! ! Interfacial!free!energy!of!emulsification! " Cohesive!force!of!the!individual!phases!=!interfacial!energy/surface!tension!at!the!boundary! between!the!immiscible!liquids!! " Interfacial!phenomena! o W!=!γΔA! §฀ W!=!surface!free!energy/work! §฀ γ!=!surface!tension! §฀ ΔA!=!increase!in!surface!area! o Cohesive!force!>!adhesive!force! o Net!inward!attraction!of!molecules!into!the!liquid! o Surface!tends!to!contract! o Results!in!interfacial!or!surface!tension!between!the!two!immiscible!phase,!contributes!to! large!interfacial!free!energy! " Agitation!forms!temporary!emulsion!! o ↑!Interfacial!tension,!↑!surface!area,!↑!surface!free!energy! o Phases!reform!when!agitation!stops!because!thermodynamically!unstable! ! ! ! ! !

Emulsifying!agents! " Role!of!emulsifying!agents! o Emulsion!formation! o Stability!–!form!a!film!around!the!dispersed!droplets ! o Reduce!interfacial!tension! " Mix!2!emulsifying!agents!–!more!stable!interfacial!films!and!good!emulsions!formed!! " Types!of!emulsifying!agents!–!surface!active!agents,!natural!products,!finely!divided!solid!particles!! ! Surface!active!agents!–!surfactants! " Most!effective!emulsifying!agents! " Polar!head:!anionic,!cationic,!non"ionic,!amphoteric! o Hydrophobic!tail!of!variable!length!! " Adsorbed!at!oil"water!interfaces!to!form!monomolecular!films!–!reduces!interfacial!tension!! " Different!uses!depending!on!size!of!tail!to!head!–!Hydrophilic"Hydrophobic!balance!(HLB)! o Low:!Antifoaming!agents,!emulsifying!agents!(water"in"oil)! o Medium:!Wetting!or!spreading!agents! o High:!Detergents,!emulsifiers!(oil"in"water),!solubilising!agents! Anionic( Cationic( NonDionic( Long!chain!organic! Long!chain!organic!cations! Long!chain!alcohols,!polyethers!or!esters!of! anions! polyhydric!alcohols! pH!dependent!–!pH!>!8! pH!dependent!–!pH!3"7!! Less!sensitive!to!pH! Only!used!in!external! Only!used!in!external! Vary!degree!of!hydrophilic!to!phobic!groups!to! preparations! preparations! alter!solubility!–!water!soluble!–!stabilises!o/w;!! oil!soluble!–!stabilises!w/o! Not!used!with!cationics! Toxicity!–!antiseptic!! Low!toxicity! Cheap! ! Expensive! ! Natural!products! " Form!a!multimolecular!film!around!the!dispersed!droplets!of!oil!in!o/w!emulsion! o Acts!as!barrier!to!coalescence!! ! Finely!divided!solid!particles! " Adsorbed!at!the!interface!between!two!immiscible!liquid!phases! " Forms!film!of!particles!around!dispersed!globules! o I.e.!particulate!film!is!formed!that!prevents!coalescence!of!the!dispersed!globules!! ! Emulsifying(agents( Surfactants( Natural( Particles( o/w( Sodium!lauryl!sulphate! Acacia! Veegum! Cetrimide! Gelatin! Bentonite! Sorbitan!esters! Cholesterol! Bentonite! w/o( Polyvalent!soaps! Wool!fat,!fatty!alcohol! Carbon!black! ! Evaluation!of!emulsion!stability! Increases!rate!of!droplets!meeting!–!thus!decreases!time"scale!over!which! Agitation( collisions!occur! Rapidly!induces!creaming!or!coalescence!in!potentially!unstable!systems! Centrifugation( Temperature(change( Alternating!between!high!and!low!temperatures,!e.g.!thaw"freezing!cycles! " Looking!for:!phase!separation,!viscosity,!electrophoretic!properties,!particle!size!and!count! " Multiple!emulsions!–!issues!with!stability!due!to!complexity!–!likely!to!coalesce!! o E.g.!w/o!emulsion!–!delayed!action!but!viscous! o w/o/w!–!bulk!phase!is!aqueous,!but!has!similar!effects! ! !

Physical!stability! " Issues!relating!to!stability!–!interfacial!tension!and!reduction!of!Gibbs!free!energy! " Formulation!considerations!–!density!of!liquids,!particle!size,!volume!density,!viscosity! Stability(issue( Explanation( Promoted(by( " Accumulation!of!droplets!at!top!or! " Large!dispersed!globules! Creaming( bottom!of!system!(depends!on!density)! " Lower!viscosity!of!continuous! " Gravitational!sedimentation! phase!–!large!difference!in!density! " Re"dispersion!achieved!by!shaking! between!the!two!phases! " Possible!breakdown!of!o/w!interphase! " Coalescence!of!dispersed!globules! " Add!emulsifier!of!opposite!type! Cracking(or( " Serious!type!of!instability! " Decomposition!or!precipitation!of! breaking( " Irreversible!–!re"dispersion!not!easily! emulsifying!agent! achieved!by!shaking! " Addition!of!common!solvent! " Disruption!of!the!emulsifying!system!–! " Microbial!action! film!surrounding!globules!is!destroyed! " Excess!disperse!phase! and!globules!tend!to!coalesce! " Temperature! " Accurate!dosage!becomes!impossible! " Globules!form!loose!aggregates! " Zeta!potential!! Flocculation( " Reversible! " Concentration!of!ions! " Possible!precursor!of!creaming! " pH!of!emulsion! coalescence!! " Surfactants! " Polymer! " Reversal!or!inversion!in!the!phases! " Alteration!in!phase"volume!ratio!–! Phase( " Diverse!phase!↔!continuous!phase! if!dispersed!phase!conc.!>!74%!of! inversion( " E.g.!o/w!emulsion!→!w/o!emulsion! total!volume! " Temperature!change! " Addition!of!substance!that!alters! solubility!of!emulsifying!agent! !

! Using!HLB!to!make!emulsions! " HLB!–!hydrophilic"lipophilic!balance!value! " Low!HLB!–!soluble!in!oil! " High!HLB!–!soluble!in!aqueous!! " HLB!values!are!additive!–!based!on!proportion!of!each!component! " HLB!value!of!Emulgant!blend!should!equal!the!required!HLB!of!oily!phase! 1. Calculate!total!required!HLB!from!oil!phase! !!!"#(!) 2. Calculate!percentages!of!emulsifies!required!using:! !"#(!)!!"#(!) ×100! 3. Calculate!amount!of!emulsifiers/emulgants!required!in!formulation! Example:( Oil(phase( Liquid!parffin! Wool!fat! Emulgant(system( Tween80!! Span80! !

mL( ! 30! 5! 5! !

HLB(required( ! 12! 10! ! 15! 4.3!

Preservatives!in!emulsions! " Microorganisms!can!cause:! o Physical!separation!of!phases! o Discolouration! o Gas!formation!and!unpleasant!odours! o Changes!in!rheological!properties! " Incompatibility!between!preservatives!and!emulsion!ingredients! o Partitioning!of!preservatives!between!oil!and!water! o Must!be!unionised!to!penetrate!bacterial!membrane!! o Must!not!bind!to!other!components!of!emulsion!system! " Adequate!concentration!to!prevent!bacterial!growth! " Preferably!bactericidal!than!bacteriostatic!! ! Microemulsions/swollen!micelles! " Clear!colloidal!solutions!(!IM!>!SC!>!Oral! High/reliable!–!IV!>!IM!>!SC!>!Oral!–! low/variable! Immediate!–!IV!>!IM!>!SC!>!Oral! –!delayed! IV!>!IM!>!SC!>!Oral! Risk!–!Oral!>!IV!=!IM!=!SC!–!no!risk!! Oral!=!IV!>!IM!>!SC! IM!>!Oral!>!SC!>!IV!

Reason( Damage!tissues/vessels! ! Parenteral!needs!sterilisation! Oral!interacts!with!enzymes/food! ! Professional!administration!! ! ! !

( Devices(for(parenteral(administration( " Made!from!stainless!steel! Needle( " Tips!are!angular!with!different!bevel!form! o Standard!bevel!–!easier!penetration,!harder!to!control!positioning! o True!short!bevel!–!easier!control! " Tube!made!from!flexible!plastic,!e.g.!PVC! Catheter(or(cannula( " Eliminate!need!for!repeated!punctures;!prevents!damage!by!needle! " Allows!for!continual!infusion! " Risk!–!infections!! " Mostly!plastic!and!are!disposable! Syringe( Implantable(devices( " Provide!long"term!access,!e.g.!chemotherapy! " Risk!of!morbidity!–!fracture!of!catheters,!infection,!irritation,!embo...