201.Controlled Release Oral Drug Delivery System

7/23/2019 201.Controlled Release Oral Drug Delivery System

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CONTROLLED RELEASE ORALDRUG DELIVERY SYSTEM


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Contents

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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

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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

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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" to&ether

+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

201.Controlled Release Oral Drug Delivery System

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