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Pharmaceutics 5

Rassoul Dinarvand

Professor of Pharmaceutics

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Pharmaceutics 5 2

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"

*

* *H

*

*

*

*

H(A (+A./ parts 0/ parts

polymerise*

*

*H

*

*

*

* *

*

H*

[

] []

[]

[]

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

*

*

*

ethacrylic acid"AA#

%oly"ethyleneglycol#dimethacrylate%(+A

polymerise*

H*

*

*

*

* *

*H

[ ] [

]

[]

[]Adhesi$e

groups

*

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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1

Drug delivery from a typical reservoir drug delivery system

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11

Drug delivery from (a) reservoir and (b) matrix swelling-controlled release systems

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12

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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1=

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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2

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