1 Final Intro Vbhv (1)

8/11/2019 1 Final Intro Vbhv (1)

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INTRODUCTION

INTRODUCTION:

An ideal dosage regimen in the drug therapy of any disease is the one, which

immediately attains the desire therapeutic concentration of drug in plasma (or at the site of

action and maintains it constant for the entire duration of treatment! This is possi"le through

administration of con#entional dosage form in a particular dose and at a particular fre$uency!

Thus drug may "e administered "y #ariety of routes in a #ariety of dosage forms! %

Drugs are more fre$uently ta&en "y oral administration! Compared with alternate

routes, the oral route of drug administration is the most popular and has "een successfully

used for con#entional deli#ery of drug! It is considered most natural, uncomplicated,

con#enient, safe means of administering drugs, greater fle'i"ility in dosage form design, ease

of production!

Among the drugs that are administered orally, solid dosage form represent the

preferred class of product! They are #ersatile, fle'i"le in dosage strength, relati#ely sta"le,

present lesser pro"lem in formulation, pac&aging and it is con#enient to manufacture, store,

handle and use! olid dosage form pro#ides "est protection to the drug against light,

temperature, humidity, o'ygen, and stress during transportation

! Amongst the solid oraldosage form ta"lets are widely used!

1 )TABLETS :

Ta"lets may "e defined as solid pharmaceutical dosage forms containing

medicament or medicaments with or without suita"le e'cipients ) prepared either "y

compression or molding!*

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INTRODUCTION

1 (a) Advantages of tablets2:

ome of the potential ad#antages of ta"lets are as follows!

They are the unit dosage form ha#ing greatest capa"ilities amongst all the oral dosage

form for the dose precision and least content #aria"ility!

Their cost is lowest amongst all the oral dosage forms!

They are the lightest and the most compact amongst all the oral dosage form!

They are easiest and cheapest for pac&aging and transportation!

They lend themsel#es to certain special release profile products such as enteric or delayed

release products!

Ta"lets are "etter suited to large+scale production than other unit oral dosage forms!

They ha#e the "est+com"ined properties of chemical, mechanical, micro"iological

sta"ility amongst all the oral dosage forms!

1(b) Classf!aton of tablets:

ased on the route of administration or the function, the ta"lets are classified as follows!-

% Ta"lets ingested orally!

Compressed ta"let

.ultiple compressed ta"let

i /ayered Ta"let

ii Compression coated Ta"let

Repeat action Ta"let

Delayed action and enteric+coated Ta"let

ugar and chocolate+coated ta"let

a 0ilm coated ta"let

" Chewa"le Ta"let

1 Ta"lets used in the oral ca#ity!

uccal Ta"let

u"lingual Ta"let

Troches and /o2enges



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INTRODUCTION

Dental cones

* Ta"lets administered "y other routes!

Implantation Ta"let

3aginal Ta"lets

- Ta"lets used to prepare solution!

4ffer#escent Ta"let

Dispensing Ta"let

5ypodermic Ta"let

Ta"lets Triturates

1) !) Tablet "an#fa!t#$ng "et%ods

Ta"lets are manufactured "y 6et granulation, Dry granulation or Direct compression

method!7

& 'et $an#laton:

6et granulation is the process in which a li$uid is added to a powder in a #essel

e$uipped with any type of agitation that will produce agglomeration or granules! These

granules after drying are compressed to form ta"lets!

& D$ $an#laton:

In this techni$ue, there is no use of li$uids! The process in#ol#es the formation of

slugs! Then the slugs are screened or milled to produce granules! The granules formed are

then compressed to form ta"lets!

& D$e!t Co*+$esson:

The term direct compression is used to define the process "y which ta"lets are

compressed directly from powder "lends of acti#e ingredient and suita"le e'cipients, which

will flow uniformly in the die ca#ity ) forms a firm compact!



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INTRODUCTION

Table No,1,1: 8rocessing teps Commonly re$uired in the 3arious Ta"let 9ranulation

preparation techni$ues7

-$o!essng

ste+s

'et $an#laton D$

$an#laton

D$e!t Co*+$esson

Raw materials

6eight

creen

.i' +

Compress

(slug

+ +

6et mass + +

.ill + +

Dry + +

.ill +

.i' +

Compress

1)d) Advantages of D$e!t Co*+$esson "et%od. :/

This process is more economical! It re$uires fewer manufacturing steps, less

processing time ) thus reduces la"our cost ) less process #alidation!

The processing steps re$uired no need of moisture, heat, and high compaction

pressure! There is an optimi2ation of ta"let disintegration, in which each primary drug particle

is li"erated from the ta"let mass ) is a#aila"le for dissolution!

Disintegrating agents li&e starch are more effecti#e when processed "y direct

compression than wet granulation techni$ue!

In the present aging society, easy+to+use dosage forms for elderly patient, whose

swallowing function is often decreased, are in great demand*-! The use of con#entional

ta"lets, capsules, and li$uid or syrup preparations were not always easy+to+use dosage forms



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INTRODUCTION

for elderly patients "ecause of there decrease motor function! imilarly the use of

con#entional ta"lets is challenging to pediatric, geriatric, and uncooperati#e patients who

may ha#e difficulty to swallow ta"lets and is also pro"lematic when water is una#aila"le or

when patients ha#e a persistent cough or gag+reflu'!

These pro"lems ha#e "een addressed "y the recent introduction of orally

disintegrating ta"lets(ODT which also &nown as A $uic&+dissol#ing ta"let (also &nown as

fast+dissol#ing, fast+dissol#ing multiparticulate, rapid+dissol#ing, mouth+dissol#ing, fast+

melting, orodispersing ta"lets is an oral ta"lets that does not re$uire water for swallowing!

.any patients e'press difficulty in swallowing ta"lets and capsules tending to noncompliance

) ineffecti#e therapy!

1, A) 0AST DISSOLIN DISINTERATIN TABLET:

Orally Disintegrating ta"lets are also called as Oro+dispersi"le ta"lets, :uic&

disintegrating ta"lets, .outh dissol#ing ta"lets, 0ast disintegrating ta"lets, Rapid dissol#ing

ta"lets, 8orous ta"lets and Rapimelts!;

A B C

0g#$e 1,1: A+ Disintegration of Oro dispersi"le ta"let after 7 seconds

+ Disintegration of Oro dispersi"le ta"let after %< seconds

C+ Disintegration of Oro dispersi"le ta"let after 1< seconds

Ad#antages of this drug deli#ery system includes administration without water ,accuracy of

dosage form , easy porta"ility ,alternati#e to li$uid dosage form ,ideal for pediatric )

geriatric patients and rapid onset of action !

Recently, 4uropean 8harmacopoeia has used the term Oro+dispersi"le ta"lets that

disperses readily and within * min in mouth "efore swallowing!;,%*

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INTRODUCTION

United tate 0ood and Drug Administration (0DA defined Oro+dispersi"le

ta"lets as, =A solid dosage form containing medicinal su"stance of acti#e ingredient which

disintegrates usually within a matter of seconds when placed upon the tongue!> ;

30ast dissol#ing ta"lets is solid dosage form that contains medicinal su"stances

and that disintegrate and dissol#e rapidly without water (within seconds when placed on the

tongue!>

The need for deli#ering drugs to patients efficiently and with few side effects has

prompted pharmaceutical companies to engage in the de#elopment of new drug deli#ery

systems! A solid dosage form that dissol#es or disintegrates rapidly in oral ca#ity, resulting

in solution or suspension without the need of water is &nown as fast dispersing dosage form

or mouth dissol#ing ta"lets! 6hen this type of ta"let is placed into the mouth, the sali#a will

ser#e to rapidly dissol#e the ta"let!

Target populations for these new fast+dissol#ing?disintegrating dosage forms ha#e

generally "een pediatric, geriatric, "edridden or de#elopmentally disa"led patients! 8atient

with persistant nausea, who are tra#eling or who ha#e little or no access of water are also

good candidates for fast dissol#ing ? disintegrating ta"lets .Other groups that may e'perience

pro"lems using con#entional oral dosage form include the mentally ill and patients who are

uncooperati#e! A difficulty in swallowing (dysphagia ta"lets or capsules is common pro"lem

among all age groups, especially in elderly and pediatrics! 0or this reasons, ta"lets that can

dissol#e or disintegrate in oral ca#ity, ha#e attracted a great deal of attention!

Orally disintegrating ta"lets are characteri2ed "y high porosity, and low hardness, when

administered an in+situ suspension is created in the oral ca#ity as the ta"let disintegrates and

is su"se$uently swallowed! ome ta"lets are designed to dissol#e in sali#a remar&a"ly fast,

within a few seconds, and are true fast+dissol#ing ta"lets! Others contain agents to enhance

the rate of ta"let disintegration in the oral ca#ity, and are more appropriately termed fast+

disintegrating ta"lets, as they may ta&e up to a minute to completely disintegrate! 6hen put

on tongue, this ta"let disintegrates instantaneously, releasing the drug, which dissol#es or

disperses in the sali#a! ome drugs are a"sor"ed from the mouth, pharyn' and oesophagus as

the sali#a passes down into the stomach! In such cases, "ioa#aila"ility of drug is significantly

greater than those o"ser#ed from con#entional ta"let dosage form%%! The disintegration time

of these ta"lets depend largely on si2e and hardness parameters!

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INTRODUCTION

On placing orodispersi"le ta"let in the mouth, sali#a ser#es to rapidly dissol#e the

dosage form! The sali#a containing the dissol#ed or dispersed medicament is then swallowed

and the drug is a"sor"ed in the normal way! ome drugs are a"sor"ed from the mouth,

pharyn' and oesophagus as the sali#a passes down into the stomach ) it may produce rapid

onset of action!%%

1, B) / ) Advantagesof Oro-dispersible Tablets

Orally disintegrating ta"lets offer all ad#antages of solid dosage forms and li$uid

dosage forms along with special ad#antages, which include %1 @

4ase of administration to patients who cannot swallow, such as the elderly, stro&e

#ictims and "edridden patients patients who should not swallow, such as renal

failure patients and who refuse to swallow, such as paediatrics, geriatric and

psychiatric patients!

8atientBs compliance for disa"led "edridden patients and for tra#elling and "usy

people who do not ha#e ready access to water!

9ood mouth feel property of .DDD helps to change the "asic #iew of

medication as "itter pill, particularly for paediatric patients due to impro#ed

taste of "itter drugs!

Con#enience of administration and accurate dosing as compared to li$uid

formulations! .ore rapid drug a"sorption from the pre+gastric area i!e! mouth, pharyn' and

oesophagus which may produce rapid onset of action!

8re+gastric a"sorption can result in impro#ed "ioa#aila"ility, reduced dose and

impro#ed clinical performance "y reducing side effects!

1,B) / ) Dsadvantages of O$o/ds+e$sble Tablet

Orally disintegrating ta"lets offer following disad#antages %* @+

Ta"lets are #ery fragile and lac& physical resistance! ecause the ta"lets are #ery

porous and low compression forces are used to prepare them! They cannot "e

pac&ed in con#entional strips or in "ottles and special pac&aging is re$uired!

itter drugs ha#e to "e taste mas&ed "y #arious techni$ues which in turn increases

the time and cost of production

The growing importance of fast dissol#ing ?disintegrating ta"let was under lined recently

when 4uropean 8harmacopoeia adopted the term =Oro+dispersi"le Ta"let> as a ta"let that to

"e placed in the mouth where it disperses rapidly "efore swallowing,

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INTRODUCTION

1,B)/) BASIC A--ROAC4ES TO DEELO- "DTS

The fast+dissol#ing property of the .DTs is attri"uted to $uic& ingress of water into

ta"let matri' resulting in rapid disintegration! 5ence, the "asic approaches to de#elop mouth

dissol#ing ta"lets include%-@

.a'imi2ing the porous structure of the ta"let matri'!

Incorporating the appropriate disintegrating agent?agents!

Using highly water+solu"le e'cipients in the formulation!

1,B) / v) +ossble benefts of o$all dsnteg$atng d$#gs,

Cln!al:

Impro#ed drug a"sorption!

0aster onset of action!

.inimi2ed first pass effect!

Impro#ed "ioa#aila"ility!

"ed!nal:

No ta"let or capsule to swallow or chew!

etter taste, no water needed!

Impro#ed safety and efficacy!

Impro#ed compliance!

Te!%n!al:

.ore accurate dosing than li$uid products!

Can use sugars and other e'cipients that are generally recogni2ed as safe!

Impro#ed sta"ility "ecause of unit+dose pac&aging!

.anufactured with common process and con#entional e$uipment!

B#sness:

/ifecycle .anagement@ re+formulation is a strategy to prolong mar&et e'clusi#ity as

it may delay or reduce generic erosion at patent e'piry!

Differentiation in a crowded mar&et

3alue+added product line e'tension

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INTRODUCTION

0or generic companies it offer the prospect of superior generic drugs in order to gain

mar&et dominance upon the e'piration of patents

Cost effecti#e drug de#elopment!

1, C) Salent feat#$e of fast dssolvng D$#g Delve$ Sste*%,1 Ste+s nvolved n S#bl*aton Te!%nolog

I &/S#ga$ Based E7!+ents%;

ugar "ased e'cipients e!g! sor"itol, manitol, de'trose, 'ylitol, fructose,

maltose etc! ha#e "een used as a "ul&ing agents! ecause of their high a$ueous solu"ility and

sweetness, which impart a pleasant mouth feel and good taste mas&ing properties, can "eused to formulate sugar+"ased mouth dissol#ing ta"let! 5owe#er, not all sugar+"ased material

ha#e fast dissolution rate and good compressi"ility!

Table No 1,2: Co**e$tall avalable *o#t% dssolvng tablets:

t$ade na*e a!tve ng$edent Catego$ *an#fa!t#$e$

8epcid R8D 0amotidine Antihistamine .erc& ) Co!,NL,UA

Nimulid .DT Nimesulide Antipyretic 8anacea iotech,New+Delhi,India

Romilast .ontelu&ast Antiasthamatic Ran"a'y /a"s /td, New Delhi, India!

Olane' Insta" Olan2apine Antipsychotic Ran"a'y /a"s /td!New Delhi India!

A maFor component of success in orally disintegrating ta"lets (ODT is good taste! If the

product does not taste good, patients and physicians will find another ODT or other product

that does taste good! ODT technology is relati#ely new to the industry and has had a

significant impact on patients of all ages!

1,8, USTATION: SENSE O0 TASTE

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INTRODUCTION

papillae are &no"li&e ele#ations found primarily on the tip and sides of the tongue! All

cicum#allate and most fungiform papillae contain taste "uds!

1,8,(a) -%solog of #staton17

Chemicals that stimulate gustatory receptor cells are &nown as tastants!

Once a chemical is dissol#ed in sali#a, it can ma&e contact with the plasma mem"rane of the

gustatory hairs, which ate the presumed site of taste transduction! The result is a receptor

potential, which is thought to cause the release of neurotransmitter "y e'ocytose of synaptic

#esicles within gustatory receptor cells! Ner#e impulses first arise in the neurons that synapse

with gustatory receptor cells!

The sodium ions (NaM in a salty food enter gustatory receptor cells #ia Na channels

in the plasma mem"rane! The accumulation of NaM inside causes depolari2ation, which opens

Ca1M channels! In turn, inflow of ca1M triggers e'ocytosis of synaptic #esicles and li"eration

of neurotransmitter! The hydrogen ions in sour tastants may flow into opening and closing of

other types of ion channels!

Other tastants, responsi"le for stimulating sweet, "itter and umani tastes, do not themsel#es

enter gustatory receptor cells! Rather they "ind to receptor on the plasmamem"rane that is

lin&ed to 9 protein!

0g#$e 1,?:.echanism of taste perception1E

1,8,(b) T%e #stato$ -at%5a1

Three cranial ner#es include a'on of first+order gustatory neurons from

taste "uds! The facial ner#e ser#ers the anterior two+third of the tongue, the glossopharyngeal

ner#e ser#es the posterior one third of the tongue, and the #agus ner#e ser#es the throat and

epiglottis! 0rom taste "uds, impulse propagates along this cranial ner#e to the medulla

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INTRODUCTION

o"longata! 0rom the medulla, some a'ons carrying taste signal proFect to the lim"ic system

and the hypothalamus, whereas others proFect from the thalamus to the primary gustatory area

in the parietal lo"e of thee cere"ral corte' gi#e rise to the conscious perception of taste!

1,


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INTRODUCTION

su"tle differences in the consistency of the food "eing masticated! 6hether the food is

creamy, rough, granular, or stic&y, the tongue is a master in differentiating those

characteristics! Conse$uently, changing the fla#or to something new may act against the

product, e#en if the effecti#eness is the same!

TASTE "AS@IN

Worst te taste of te medication, te better te cure! was once the pre#ailing

attitude1;! Today this trend has changed and great importance is gi#en to the organoleptic

characteristics of pharmaceutical products i!e! mainly appearance, odor and taste! .as&ing

the unpleasant taste of a drug impro#es the compliance of the patient and product #alue!

Administration of a drug orally ha#ing "itter and o"no'ious taste with accepta"le le#el of

palata"ility is a challenge to the pharmacist in the present world, especially in paediatric and

geriatric formulation! Thus taste mas&ing in the present day pharmaceutical industry has

"ecome a potential tool to impro#e patient compliance and commercial success of the

product!

0ormulationBs organoleptic properties i!e!taste ,mouth feel and appearance are of considera"le

importance in differentiating products in the mar&et and can ultimately determine the success,or otherwise, of a product!

.ore than 7


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INTRODUCTION

8harmaceutical companies are commercially moti#ated to in#est time, money and resources

in de#eloping palata"le, pleasant tasting products "ecause good tasting products*;@

4nhance patient compliance

8ro#ide a competiti#e ad#antage when a therapeutic category is crowded with

similar products e!g! anti+infecti#e category etc!

8ro#ide "rand recognition to com"at pri#ate+la"el competition!

Taste mas&ing technologies rely on pre#enting interaction "etween the drug molecule

and the oral mucosal surface! y creating a physical "arrier around each particle, drug

su"stance can "e pre#ented from going into solution and interacting directly with taste

receptors!

In the pharmaceutical industry, taste+mas&ing science "roadly co#ers physiological

and physicochemical approaches to pre#ent Acti#e 8harmaceutical Ingredient (A8I or drugs

from interacting with taste "uds there"y eliminating or reducing negati#e sensory response!

1,>) ene$al a++$oa!%es to taste *as6ng*%, *P, -

are diluents &nown for their taste mas&ing characteristics! Artificial sweetener li&e

neohesperidine dihydrochalcone, which is a "itterness suppressor and fla#our modifier, elicits

a #ery intense sweet taste hesperidine dihydrochalcone -B+Q+D+glucoside has the a"ility to

reduce the perception of "itterness!

!) Taste *as6ng b n%btng btte$ness



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INTRODUCTION

/ipoproteins composed of phosphatidic acid and "eta+lacto glo"ulin

were effecti#e in suppressing the "itter taste of drugs such as caffeine, propranolol,

prometha2ine and $uinine! The salty taste of sodium chloride and sweet taste of sucrose were

not inhi"ited "y the lipoproteins! The addition of phosphorylated amino acids such as

phosphotyrosine and phosphoserine to mi'tures of I"uprofen, Acetaminophen,

De'tromethorphan hydrochloride, 8seudoephedrine hydrochloride and Chlorpheniramine

maleate inhi"ited the unpleasant taste of drugs without su"stantially affecting the o#erall true

taste of the formulations!

d) Taste *as6ng b !oatng-1

Coating is an e'tremely useful techni$ue for a num"er of applications

in the pharmaceutical field! Although it is used primarily for production of sustained release,

gastro+resistant dosage forms, it also has maFor application in mas&ing the unpleasant taste!

.erely applying thic&er layer of coating material can "e ineffecti#e in taste mas&ing of

certain drugs with o"Fectiona"le taste! Thic& coating can cause pro"lems "oth in terms of si2e

and coat apart from "eing pro"lematic in getting the desired release profile of the drug! Taste

mas&ing of I"uprofen has "een successfully achie#ed "y using the air suspension coating

techni$ue to form microcapsules, which comprises of a pharmaceutical core of crystalline

I"uprofen and a methacrylic acid copolymer coating that pro#ides chewa"le taste mas&ed

characteristics! The methacrylic acid copolymer has a rapid rate of dissolution at a p5 of

a"out 7!7!

e) Taste *as6ng b $%eolog!al *odf!aton-1

A$ueous dispersions of gums such as acacia, tragacanth, 'anthan gum or

synthetic polymers such as polyethylene glycols, hydro'ypropyl methyl cellulose, hydro'yl

ethyl cellulose, are used to increase the #iscosity, which lowers diffusion of "itter su"stances

from the sali#a to the taste "uds! Com"ination of polyethylene glycol (849 and sodium

car"o'y methyl cellulose (Na+C.C were used to mas& the unpleasant taste of drugs such as

guaifenesin, pseudoephedrine hydrochloride, de'tromethorphan and I"uprofen!

f) Taste *as6ng b salt +$e+a$aton o$ f#n!tonal g$o#+ *odf!aton

This approach in#ol#es taste mas&ing of the "itter drugs "y either

decreasing solu"ility or "y increasing hydropho"icity and there"y reducing contact of "itter

drugs with the taste "uds! This approach differs from others in that attempt is made to modify

the chemical composition of the drug su"stance itself, so as to render it less solu"le in sali#a



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INTRODUCTION

and there"y less stimulating to the taste "uds, or to o"tain a tasteless or less "itter form! The

al&ylo'yal&yl car"onates of Clarithromycin ha#e remar&a"ly reduced!

g) Taste *as6ng b n!l#son !o*+le7aton

In inclusion comple' formation, the drug molecule fits into the ca#ity of

a comple'ing agent i!e! the host molecule forming a sta"le comple'! The comple'ing agent is

capa"le of mas&ing the "itter taste of drug "y either decreasing its oral solu"ility on ingestion

or decreasing the amount of drug particles e'posed to taste "uds, there"y reducing the

perception of "itter taste! 3an der 6aals forces are mainly in#ol#ed in inclusion comple'es!

+Cyclode'trin is most widely used comple'ing agent for inclusion type comple'es! It is

sweet, nonto'ic, cyclic oligosaccharide o"tained from starch!

%) Taste abate*ent b Ion E7!%ange Resns-1

.ost of the "itter drugs ha#e nitrogen atom and amine as a functional

group, which is the cause of their o"no'ious taste! If the nitrogen atom and functional groups

are "loc&ed "y comple' formation the "itterness of the drug reduces drastically!

8harmaceutical industry has done this type of comple' formation "y con#erting the drug to

stearates and estolate! ut now days the use of ion e'change resin is done to "loc& the

functional group responsi"le for causing the "itter taste "y forming comple' "etween ione'change resin and the drug! 0urther "ecause of the comple', the drug doesnBt release in the

sali#a! Thus the resin reduces the drug and taste "uds interaction!

A drug@ resin comple' is made from the "itter drugs ) ion + e'change resins!

The nature of the drug@ resin comple' is such that the a#erage p5 of E! and Cation

concentration of a"out -< me$? lit in sali#a are not a"le to "rea& the drug@ resin comple' "ut

it is wea& enough to "e "ro&en down "y the hydrochloric acid present in the stomach! Thus

the drug@ resin comple' is a"solutely tasteless and sta"le, with no after taste, "ut at the same

time its "ioa#aila"ility is not affected!

6ith taste mas&ing technology it is possi"le to ma&e Tasteless Drug@ resin Comple'

of #arious "itter drugs and can "e used these drug@ resin comple' in formulating not only the

con#entional dosage forms li&e ta"lets and capsules, "ut also other dosage forms li&e

dispersi"le ta"lets, chewa"le ta"lets and oral suspensions!

1,. ) ION/EC4ANE RESIN (IER)



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INTRODUCTION

Ion e'change can "e define as a re#ersi"le process in which ions of li&e sign are

e'changed "etween li$uid and solid, a highly insolu"le "ody in contact with it71! Ion+

e'change resins are water+insolu"le, cross+lin&ed polymers containing co#alently "ound

salt forming groups in repeating positions on the polymer chain!7*

Ion e'change resin may "e define as a special type of a polyelectrolyte and consists of free

dimensional polymeric hydrocar"on networ& to which are "onded a large num"er of

electrically charged groups, such as O*+(ulphonate group or a N(C5*-

M (:uarernary

ammonium group!7- The most common properties of all ion e'changers which ha#e "een

used&

They are almost insolu"le in water and organic sol#ents, li&e "en2ene,

car"on tetrachloride, ether, etc!

They are comple' in nature and in fact they are polymeric!

They contain acti#e of counter ions that will e'change re#ersi"ility

with other ions in a surrounding solution without any su"stantial change in

the materials!

0igure %!P@ Classf!aton of Ion E7!%ange Resns>

1,.,a) T%eo$ of on e7!%ange :

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INTRODUCTION

Ion e'change is a stoichiometric process in which any counter ions that lea#e the

ion e'change are replaced "y an e$ui#alent amount of other counter ions! This is a

conse$uence of the electro neutrality re$uirement! The ion e'change is essentially a

diffusion process, "ut also has relation to chemical reaction &inetics! Usually the ion

e'changers are selecti#e they ta&e up some counter ions in preference to others! The rate+

determining step in ion e'change is diffusion either within the ion+e'changer itself or in

the diffusion "oundary layer! Rechen"erg proposed that at low concentration of counter

ion, the rate of e'change is controlled "y film diffusion and at high concentrations "y

particle diffusion! The e$uili"rium distri"ution of the drug species "etween the resin and

e'ternal solution phases results from "oth electrostatic and hydropho"ic interactions! In the

ion e'change resins the ions are &nown to "ind to the ion+e'changer "y two mechanisms!

Drug in an ionic form (usually in solution is mi'ed with the appropriate I4R to

form a comple' , &nown as HresinateB! The performance of resinate is go#erned "y se#eral

factor, such as --@

p5 and temperature of the drug solution

.olecular weight and charge intensity of the drug and I4R

.i'ing speed Ionic strength of the drug solution

Degree of cross lin&ing and particle si2e of the I4R

Nature of sol#ent

Contact time "etween the drug species and the I4R

Drug release from Drug@ resin comple' (Resinate depends upon two factors-1@

%! The ionic en#ironment (i!e! p5 and electrolyte concentration within the

gastrointestinal tract!

1! The properties of resin

Drug molecules attached to the resins are released "y appropriate

charged ions in the gastrointestinal tract, followed "y diffusion of free drug molecules

out of the resin as shown "elow!

Resin+ Drug MM SM Resin++++++SM M Drug M

Resin + Drug MM GM Resin+ ++++++GMM DrugM

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INTRODUCTION

6here S and G are ions in the gastrointestinal tract

0g#$e 1,1: 0actors that affect I4R process in#ol#ed in the deli#ery of cationic drug--

1,.,b) -$o+e$tes of Ion E7!%ange Resns--

1, -a$t!le s9e: The rate of ion e'change reactions depends on the si2e of resin particles!

Decreasing the si2e significantly decreases the time re$uired for the reaction to reach

e$uili"rium with surrounding medium! I4Rs are a#aila"le in wide si2e range from 1 to *

mm spherical "eads to powder as fine as few microns!

2, -o$ost and s5ellng: 8orosity is defined as the ratio of the #olume of the material to

its mass! The limiting si2e of ions that can penetrate into the resin matri' depends strongly

on the porosity, which depends mainly on the amount of cross +lin&ing agent, and also on

polymeri2ation process! welling is directly proportional to num"er of hydrophilic

functional groups and in#ersely proportional to degree of cross+lin&ing!

8, C$oss/ln6ng: 8ercentage of cross+lin&ing affects purely physical structures of resin

particles! Resins with low cross+lin&ing can swell into structure that is soft and gelatinous

when ta&e up water, while resins with high cross lin&age are somewhat hard and "rittle!


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INTRODUCTION

>, A!d base st$engt%: Resin containing sulfonic, phosphoric or car"o'ylic acid e'change

groups ha#e appro'imate pJa #alues of 1+*, -+E respecti#ely! Anionic e'changers are

$uaternary, tertiary or secondary ammonium groups ha#ing apparent pJa #alues of %*, +

P and 7 to P respecti#ely! Acid "ase strength is significant for the reason that the strength

of "ond and su"se$uent rate of release of drug depends on this strength also the p5

en#ironment needed for loading and release of drug can "e predicted!

., Sele!tvt of $esn fo$ !o#nte$ on: ince ion e'change in#ol#es electrostatic forces,

selecti#ity mainly depends on relati#e charge, and ionic radius of hydrated ions competing

for an e'change site and to some e'tent on hydropho"icity of competitor ion!

?, Stablt: The I4Rs are remar&a"ly inert su"stances! They are resistant to attac& "y

chemicals and heat to large e'tent! The limitation is degradation in presence of strong

gamma rays!

, To7!t: The resins are insolu"le solids that are not a"sor"ed "y the "ody hence, they

do not ha#e significant associated side effects or to'icity! 5owe#er, commercial products

canBt "e used as such as they contain impurities that can cause to'icity! Therefore careful

purification of resins is re$uired prior to treatment with drugs,

1,.,!) E#lb$#* +%eno*enon

( drug can be loaded onto an ion-e)change resin by an

e)changing reaction* and hence a drug-resin comple) is formed& The

principal properties of these resins are their e'change capacity to e'change its insolu"le

ions with those in solution! olu"le ions may "e remo#ed from the solution through

e'change with the counter ions a"sor"ed on the resin as illustrated in this e$uation@

Re+ o*+NaMDrugM Re+ o*+DrugMM NaM

Re+N (C5**cl + MDrugM Re+N(C5**M +Drug+ M cl

These are e$uili"rium reactions in which e'tent of e'change is go#erned "y the

relati#e affinity of the resin for particular ions! Relati#e affinity "etween ions may "e

e'pressed as a selecti#e coefficient deri#ed from the mass action e'pression as gi#en

"elow!

JD. VDWrV.W? VDWV.Wr

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INTRODUCTION

6here,

VDWr drug concentration in resin!

V.W counter ion concentration in the solution!

VDW drug concentration in the solution

V.Wr counter ion concentration in resin!

1,.,d) E7!%ange !a+a!t

The e'change capacity refers to num"er of ionic sites per unit weight of or #olume

of ion e'change resin (me$! per gram! The weight "asis #alue (me$! per gram is

generally much higher than the #olume "ased e'change capacity since the wet resin is

highly hydrated! The e'change capacity may limit the amount of drug that may "ea"sor"ed on a resin and hence the potency of a comple'! Car"o'ylic acid resins are

deri#ed from the acrylic acid polymer and ha#e higher e'change capacities (a"out %< me$!

per gram than sulfonic acid (a"out - me$! per gram or amine resins "ecause of "ul&ier

ionic su"stitute and polystyrene matri'! Therefore, higher drug percentage may often "e

achie#ed with car"o'ylic acid resins!

1.7 ) Ion E7!%ange Resn : A++l!atons n D$#g Delve$ Resea$!%

%! Taste mas&ing1! Ta"let disintegration

*! Drug sta"ili2ation

-! ustained release

7! Targeted drug deli#ery

Table No, 1,8: Drugs taste mas&ed "y #arious grades of ion e'change resin-1!

Na*e of t%e d$#gIon e7!%ange $esn

Ciproflo'acin Indion+1*-

A2ithromycin Indion+1%-

Chloro$uine 8hosphate Indion+1*-

Oflo'acin Tulsion+**7

De'tromethorphan 5ydro"romide Indion+1*-

:uinine ulphate Indion+1


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INTRODUCTION

Documents

1 Final Intro Vbhv (1)