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7/23/2019 201.Controlled Release Oral Drug Delivery System
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1
CONTROLLED RELEASE ORALDRUG DELIVERY SYSTEM
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Contents
2
Introduction
Advantages
Disadvantages
Types
References
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Terminology:
Sustained Release Drug Delivery Systems:
Sustained release constitutes any dosage form that provides
medication over an extended time to maintain therapeutic blood or tissue
levels of the drug.
Controlled Release Drug Delivery Systems:
Controlled drug delivery is one which delivers the drug at a predetermined rate,
for locally or systemically, for a specified period of time.
Continuous oral delivery of drugs at predictable & reproducible kinetics for
predetermined period throughout the course of !T.
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Repeat-Action drug delivery systems:
"epeat#action tablets are an alternative method of sustained release inwhich multiple doses of drug are contained within a dosage form, and each dose isreleased at a periodic interval.
Delayed Release Drug Delivery Systems:
$elayed release systems may not be sustaining but these dosage forms
maintains the drug within the dosage form for some time before release.
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Plasma concentration timeprofle
5
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6
%atient comfort and compliance
Therapeutic advantage
"eduction in adverse side effects and improvement in
tolerability
"eduction in healthcare cost
aximum utili'ation of drug enabling reduction in total
amount of dose administered
WHY CONTROLLED RELEASE
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Oral CR
60%
Implant
10%
Inhalation
27%
Transdermal
8%All Other
2%
US Controlled Drug Delivery MarketUS Controlled Drug Delivery Market
Drug delivery market dominated by oral delivery systems
Source: IMS America Drug delivery based !roducts7
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Characteristics that sho!" #e$ossesse" #% the Dr& 'o!ec!e
(
Dose !ess tha) 1**'&
Lo+ $rotei) #i)"i)& $ro$erties
E,cie)t GI a#sor$tio)
-a!. !i.e a#ot /06hrs
Lar&er thera$etic i)"e
Should not possess:
-a!. !i.e !ess tha) 2hrs or &reater tha) ( hrs
-i&h $ote)c%
Greater "ose
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h%sicoche'ica! ro$erties O. A Dr&I)3e)ci)& Dr& ro"ct Desi&) a)"
er.or'a)ce4
Aqueous solubility:
Tetracycline dissolves to a greater extent in the stomach
than in the intestine, although it is best absorbed in the
intestine. (ence, poor candidates for controlled release
systems, unless the system is capable of retaining the drug in
the stomach and gradually releasing it to the small intestine orunless the solubility is made higher and independent of the
external environment by encapsulating the drug with an acid.
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Partition Coefficient and Molecular Size:
$rugs with extremely high partition coefficient )very oilsoluble* readily penetrate the membranes but are unable to
proceed further and vice versa with drugs with very low
partition coefficient )excessive a+ueous solubility*.
Protein inding:
any drugs bind to plasma proteins. $rug protein bindingcan serve as depot for the drug producing a prolonged release
profiles, especially if a high degree of drug binding occurs.
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iological -actors !nfluencing $esign and %erformance ofControlled "elease Systems:
Absorption: minoglycosides such as gentamycin and kanamycin.
"iboflavin is absorbed by an active transport process in the upper part of the !T.
Distribution: The distribution of drugs into tissues can be one important factor in the overall
drug elimination kinetics, since it not only lowers the concentration of circulating drug butit also can be rate#limiting in its e+uilibration with blood and extracellular fluid.
Metabolism:
(ydrala'ine is metaboli'ed by the intestinal wall and/or the liver during
absorption, although it is well absorbed.
!n contrast, romocriptine is incompletely absorbed, the poor bioavailability of
which is further reduced by first pass metabolism in the liver resulting in an absolute
bioavailability of only 01.
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Role of Disease State: Controlled release spirin tablets in the proper dosage provided
and maintained blood levels at therapeutic concentration over 2#34hrs, a duration
that was about twice as long as that provided by conventional tablets.
Role of Circaian R!"t!m: Several biological processes and disease states shown to be
influenced by circadian rythms. s a result, the response to certain drugs also
follows cicadian rythms. $igitalis glycosides, antianginal, diuretics, %sychoactive drugs such
as amphetamines, arbiturates, carbama'epine, ethyl alcohol and chlordia'epoxide
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Design principle o sustained releasedosage orms or release rate and
dose considerations:
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Advantages
1
Tota! "ose is !o+
Re"ce" GI si"e eects
Re"ce" "osi)& .re8e)c%
9etter $atie)t acce$ta)ce a)" co'$!ia)ce
Less 3ctatio) at $!as'a "r& !e:e!s
More )i.or' "r& eect
I'$ro:e" e,cac%;sa.et% ratio
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Disadvantages
15
Dose dumping.
Reduced potential for accurate dose adjustment.
Need of additional patient education.
Stability problem.
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Types of Oral drug delivery System
16
1.Dissolution controlled Release Dosage Forms
2.Diffusion Controlled Release Dosage Forms
3.Combination of both dissolution diffusion.
!."smotic pressure controlled system
#.$on%&'change Resins
(.p) $ndependent systems
*.+ltered Density Formulations
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Dissolution Definition:
17
ass transfer from solid to li+uid.
"ate determining step: $iffusion from solid to li+uid.
Several theories to explain dissolution 5
Diffusion layer theory
Surface renewal theory
Limited solvation theory.
-or (ighly water soluble drugs
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Matrix Type
1(
lso called as onolith dissolution controlledsystem.
Controlled dissolution by:
3.ltering porosity of tablet.
6.$ecreasing its wettebility.
7.$issolving at slower rate.
-irst order drug release.
$rug release determined by dissolution rate ofpolymer.
8xamples: $imetane extencaps, $imetappextentabs.
So!#!e "r&
S!o+!%"isso!:i)&'atri
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Encapsulation
1VC? .att%
'ateria!s@
o$!ar .or sstai)i)& the re!ease o. hi&h!%+ater so!#!e "r&s
The 'ateria!s .or sch 'atrices are &e)era!!%h%"ro$hi!ic &' a)" 'a% #e o. )atra! ori&i)>&ar &'? tra&aca)th@? se'i s%)thetic>-MC? CMC? a)tha' &'@or s%)thetic>o!%ar%!a'i"e@0the "r& a)" &' are &ra)!ate" toðer
+ith a so!:e)t sch as a!coho!? a)"co'$resse" i) to ta#!et21
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The re!ease 'echa)is'B
BBB the re!ease o. "r& .ro' the S+e!!a#!e 'atri
s%ste' i)itia!!% "eh%"rate" h%"ro&e! i):o!:es co)ti)os
a#sor$tio) o. +ater >res!ti)& i) h%"ratio)? &e!!i)& a)"
s+e!!i)& o. &'@ a)" "esor$tio) o. "r& :ia a s+e!!i)&
co)tro!!e" "isio) 'echa)is' A)" .or's G!ass% h%"ro&e!
22
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!)Reservoir typeDiusion controlled
systemThese s%ste's are ha!!o+co)tai)i)& a) i))er core o. "r&srro)"e" i) a +ater i)so!#!e$o!%'er 'e'#ra)eThe $o!%'er ca) #e a$$!ie" #%coati)& or 'icroe)ca$s!atio)tech)i8es
Mecha)is' $artitio)i)& the "r&i) to the 'e'#ra)e +ith
s#se8e)t re!ease i) tosrro)"i)& 3i" #% "isio)
o!%'ers B-C? eth%! ce!!!ose$o!%:i)%! acetate
Disadvantage..Dose dumping
2/
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Dissolution Diffusion ControlledRelease system
2
Drug encased in a partially solublemembrane.
,ores are created due to dissolutionof parts of membrane.
$t permits entry of a-ueous mediuminto core drug dissolution.
Diffusion of dissoled drug out ofsystem.
&'% &thyl cellulose ,/, mi'turedissoles in 0ater create pores ofinsoluble ethyl cellulose membrane.
I)so!#!e'e'#ra)e
ore create" #%"isso!tio) o.so!#!e .ractio) o.'e'#ra)e
E)tr% o."isso!tio)3i"
Dr&"isio)
ION E!"#N$E %E&IN& D%'$ !O(P
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ION-E!"#N$E %E&IN& D%'$ !O(P
!on#exchange systems generally use resins composed of water#insoluble cross#linkedpolymers.
These polymers contain salt#forming functional groups repeating positions on thepolymer chain.
The drug is bound to resin and released by exchanging with appropriately charged ionsin contact with the ion#exchange groups.
Resin$ % ru&%$ '%resin$% '% $ ru&%
Resin% % ru&$ $ Y$resin% % Y$$ ru&$
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TYPES OF RESI!TES I OR!L "DDS
#(S)M*LE RES)NATES:
Suspended in 8S: %an coating, ir Suspension, !nterfacial %olymeri'ation, Solvent 8vaporation
"#P$%%&'%$('C S)S($M:#(DR,- "8S!;T8 !S %"8T"8T8$
?!T( %8 @44.
6.%"8T"8T8$ "8S!;T8S "8 T(8; C9T8$ ?!T( 8T(A