drug delivery introduction
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Pharmaceutics 5
Rassoul Dinarvand
Professor of Pharmaceutics
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Chemical engineering◦ Less soluble melts
◦ Prodrugs
◦ Targeting linkages (MAB)
◦ Peglation
Pharmaceutical engineering
◦ !il vehicles◦ Li"osomes
◦ Polmeric deliver
◦ Cell based drug deliver
Particle engineering◦ #olid li"id "articles
◦ Dendrimers
Mechanical engineering◦ Mechanical "um"s
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• Large molecule composed of a number of sub-units
- Natural e.g. alginates,
- synthetic e.g. poly(HMPA)
- unction go!erne" #y num#er an" arrangement o$ constitutional repeat
units e.g. –[A-]n, -[A-B-]n, -[A-A] n-[B-B] m , --A-A-B-A-B-B-A-
• How are they made?- Processing o$ natural pro"ucts % alginates $rom sea&ee"s, celluloses
$rom plants
- 'ynthesis $rom chemical $ee"stocs % poly(ole$ins), nylons,
poly(esters)
• How can they help?- Protection o$ therapeutic compoun" "uring passage through #o"y, as
encapsulant or carrier.
- Me"iator or acti!ator o$ controlle" release
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• atri! "onolithic# de$ices
- $ilms &ith the "rug in a polymer matri!- asy to $a#ricate, typically #y simple mi*ing o$ polymer an" "rug
- *ample+ u"ragit '1 polymer, mi*e" &ith sor#itol an" lur#ipro$en
• %olymer drug con&ugates
- Polymer attache" to "rug #y (co!alent) sacri$icial liner
- *ample+ Paclita*el-al#umin conugate in the maret
/oceta*el-al#umin conugate un"er in!estigation
• 'eser$oir de$ices
- /rug containe" by the polymer
- elease is usually "i$$usion controlle" (ician) i.e. J = -D C &here 0 $lu*,
component o$ concentration across mem#rane o$ "e$ine" area, an" ∇ is a "i$$erential !ector
operator
- *ample+ Pharma3ome4M 4heophylline release
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• Biodegradable polymers
- Polymer "egra"es in vivo to release the "rug- 'imple release mechanism, #ut "i$$icult to o#tain $ine control o!er "egra"ation
- /oes not in!oe an in$lammatory or to*ic response.
- s meta#oli3e" in the #o"y a$ter $ul$illing its purpose, lea!ing no trace
• (!amples in use
- esomer (P67A)
- 8icryl (P67A)
• )ommon biodegradable polymers
- Poly(lacti"e-co-glycoli"e) (P67A)
- Poly(hy"ro*y#utyrate-co !alerate) (9iopol)
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Hydrogels
• 4hree-"imensional, hy"rophilic polymeric net&ors, s&ollen &ith&ater
• ross-lining #et&een polymer chains "etermines s&elling an" gel
$le*i#ility
• Natural or synthetic "eri!e" % !ery large num#er o$ hy"rogels ha!e
#een pro"uce"
• onic (aci"ic, #asic) or neutral "epen"ent on "esire" application
• Inherently biocompatible % strongly hy"rate"
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H(A (+A./ parts 0/ parts
polymerise*
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onomer "water-soluble# )ross-lin1er Hydrogel
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ucoadhesi$es
• 2nd a&or class of polymer drug deli$ery $ehicles
- 'imilar in "esign $eatures to hy"rogels (su#-class)
- A#ility to localise at mucus mem#rane !ia a"hesi!e interactions
- ontain $unctional groups $or #in"ing to mucosal sur$aces %
primarily H-#on"ing
- Pen"ant chains $or intimate contact an" inter"igitation &ith
mucins
- Inherently biocompatible % strongly hy"rate"
*
*H
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ethacrylic acid"AA#
%oly"ethyleneglycol#dimethacrylate%(+A
polymerise*
H*
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[]Adhesi$e
groups
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n
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Controlled release im"lies controlled release of
drugs from "olmer drug deliver sstems(DD#)
T"e of "olmer◦ $on%degradable & Degradable
T"e of Design
Reservoir Matri'
Release mechanisms◦ Diusion & "olmer degradation & combination
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Drug delivery from a typical matrix drug delivery system
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Drug delivery from a typical reservoir drug delivery system
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Drug delivery from (a) reservoir and (b) matrix swelling-controlled release systems
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Drug delivery from environmentally sensitive release systems.
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1<
Molecular gates for the delivery of insulin triggered by the presence of glucose
in the bloodstream
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Drug delivery from (a) bulk-eroding and (b) surface-eroding biodegradable systems
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Particulatesstems
◦ $ano"articles
$anoca"sules $anos"heres
◦ Micro"articles Micros"heres
Microca"sules
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ilms Membranes ibers Rods Beads Discs Clinders
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#imultaneous drug loading and"olmerisation&device fabrication
Drug loading after device fabrication◦
Drug u"take b "olmeric device *henimmersed in drug saturated solution
◦ Mechanical drug loading
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DiusionConcentration gradient in "olmeric
matri'
Chemical reactionPolmer biodegradation
#olvent eectRelease of soluble drugs in hdrogels
Mechanical release
Drug release from mechanical devicessuch as "um"s
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+m"lants +n,ectables Transdermal
!ral $asal !"hthalmic
-aginal
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3olid tumor
Apply magnetic$iel" to concentrate
particles
Mo"ulate $iel" torelease "rug $rom
particles
nect NPs 8,
NP &ill circulate through
the #loo" stream
Pharmaceutics 5