International Journal of Pharmacy and Pharmaceutical Sciences

ISSN- 0975-1491 Vol 2, Issue 4, 2010

ResearchArticle

EFFECTOFSUPERDISINTEGRATINGAGENTANDOSMOGENSONCIPROFLOXACINLOADED NATURALLYOCCURRINGBIODEGRADABLECOATEDTABLETSFORCOLONTARGETING

ABHISHEKKUMARJAIN1*,CHANDRAPRAKASHJAIN1
1

DepartmentofPharmaceuticalScience,M.L.SukahadiaUniversity,Udaipur,Rajasthan,India,313001,Email:abhi181281@yahoo.com Received:20May2010,RevisedandAccepted:26Jun2010

ABSTRACT The aim of present study is to develop a controlled release site specific dosage form as tablet for treatment of colonic disease. There were two different phenomena used during the formulation of tablets. The first one was using of different super disintegrating agents (sodium starch glycollate,sodiumcellulosemethylcelluloseandsodiumlauryl sulphate)asexcipientinthe coretablet.Theamount of superdisintegrantinthe tabletandthecoatweightwerevariedfortheformulationofasuitabletimecontrolledreleasesystem.Thesecondwasdevelopmentofdifferent osmogenbasedcoretabletsfordrugdeliveryatthespecificregionofthecolon.Thesecoretabletswereagaincoatedwithnaturalbiocompatible polysaccharidepolymersasacoatingagent.Ciprofloxacinwasusedasamodeldrugforpresentstudy.Invitrodrugreleasestudiesshowedthat superdisintegratingagent(sodiumlaurylsulphate3.0mg)containingformulationwasmoreeffectivethanother,becauseitshowed bursteffect andthereforearapiddrugreleasestartascomparedwithsodiumstarchglycollate3.0mgcontainingformulation.Thefinalresultindicatedallcore tablets release drug fast, when it came at the colonic region within 12h and system follows as sustained drug delivery. Osmotic tablets were formulatedwithhighconcentrationofosmogens;sodiumchloride(OMSC)andpotassiumchloride(OMKC)andthencoatedwithpolysaccharide materials.Thesealsowerefoundtobeusefulforprovidingasustaineddeliveryofnearly97%ofthedrugwithin12h,butthereleaseistoomuch fast than formulation prepared with all superdisintegranting agents. The coat weight required for protection in the upper gastrointestinal conditionsvariedfrom1020%oftotalweightofeachtablets. Keywords: Ciprofloxacin, Super disintegrating agents; Sodium lauryl sulphate, Sodium starch glycollate, Sodium carboxy methyl cellulose, Osmogen;PotassiumChloride,SodiumChloride. INTRODUCTION Colonspecificdrugdeliveryismostlyusedforthetreatmentofcolonic diseases,suchas inflammatory or infectious bowel diseases or colon cancer1.Fromthelastfewdecades,manyresearchershaveinterestin the field of colonspecific drug delivery for treatment of colonic disease. The interest of research is because the colon has a large amount of lymphoma tissue (which would facilitate a direct absorption into the blood), negligible brush border membrane peptidase activity, and much less pancreatic enzymatic activity as comparedwiththesmallintestine24.Thecolonalsoisconsideredasa suitablesitefordeliveryofproteins,peptides,andacidlabiledrugs5. Targeting of drugs specifically to colon is advantageous in the treatmentofdiseasesassociatedwiththecolonsuchasamoebiasis, Crohns diseases, ulcerative colitis, and colorectal cancer. Site specific drug delivery systems are the main focuses of oral controlledrelease solid dosage forms6. The formulation based on approach slow delivery at the beginning of the dissolution process andfastreleaserateofdrugindefinitepartsofthegastrointestinal tract and intestine increase local therapeutic effect 7. Pulsatile drug delivery systems are characterized by two release phases. A first phase is nil or little amount of drug being released and a second phase is completely release of drug within a short period of time afteralagtime.Thereleasecanbeeithertime,orsitecontrolled8. Among many approaches for oral drug delivery to the colon site, pectin or their combination with natural biodegradable polymers based coated formulations show best effect, because they remain intact in the upper gastrointestinal tract and are degraded in the colonbycolonicmicoflora1. Entericcoated systems provide the protection for drug release in the stomach. A thicker coat of these polymers on the delivery systemsincreasealagphaseoftheformulation9Alternativelysome drugreleaseretardingagentscanbeintroducedintotheformulation by Sinha10. Osmotic agents generally have been used in the formulationtoshowbursteffect. Thepresentstudywasdevelopedbyusingsuperdisintegrantsinthe formulationasburstingagents,andthesewereevaluatedagainstthe osmogensbasedsystemstoshowburstingeffect.Invitrodrugrelease studieswereperformedanddrugreleasebehaviorcharacterized.The aim of the present system was to provide a rapid drug release with sustained effect after a lag time of 56 hr into the proximal part of colon.Becausetheproximalpartofcolonisthemostabsorptivesiteof the colonsincethe chyme is in a semiliquid form when formulation reachesatthispart.Thus,thechanceofdrugabsorptionfromthissite is maximum11. The thicker coat of naturally biodegradable polymers providing a lag or silent phase of 56 h would be able to carry the dosage form into theproximal colon. The dosage form was designed with superdisintegrants and or osmotic agents (osmogens) for investigationrapidburstingeffectofcoatedformulation,whensystem reaches into the proximal part of colon. The dissolution of the polymeric coating starts and a pressure starts to build up inside the tablet.Whenthepressureexceeds,thetabletburstsduringthesystem transit through stomach and small intestine. The duration of this lag phasecanbeincreasedordecreaseddependinguponthesite,where drugreleaseisdesiredforlocaleffectofdrugfortreatmentofcolonic disease. The bursting time of the tablet depend on coat weight thickness, combination of coating polymers, the quantity of superdisintegrantand the type ofosmogen used.Thequantity ofthe superdisintegrant in the tablet and the coat weight was varied and wereevaluatedfortheirdrugreleasecharacteristics. MATERIALSANDMETHODS Materials Ciprofloxacin and Microcrystalline cellulose (Avicel PH 102) were obtainedasgiftsamplefromPlethicopharmaceuticalpvt.Ltd,(Indore, India).Sodiumstarchglycollateandsodiumcarboxymethylcellulose were obtained from plethico pharmaceutical pvt. Ltd., Indore, India. Other ingredients such as lubricant, glidant, and plasticizer used to prepare the tablet were of standard Pharmacopoeial grade and all chemicalreagentsusedwereofanalyticalgrade. Method Solubilitydeterminationofciprofloxacin Thesolubilitypropertiesofciprofloxacinweredeterminedinwater andatvariouspHs.Sodiumthiosulphatewasaddedtothemedium, when pH 6.8 and pH 7.4 phosphate buffers were used to prevent oxidation. In earlier studies, sodium bisulphite, ascorbic acid and thioglycolicacidwerealsoused,buttheywereabandoned,because ofpHalterations.However,whensodiumthiosulphatewasusedas anantioxidant,itdidnotaffectthepHofthemedium.Therefore,the

Jainetal. IntJPharmPharmSci,Vol2,Issue4,160165 addition of sodium thiosulphate was kept constant for further studies, when the pH 6.8 or 7.4 buffers were used. The excess amountofciprofloxacinwasaddedto100mlofmediumandstirred continuouslyovernightat370.5C. The solubility values of ciprofloxacin in various media were determinedspectrophotometrically.TheUVdetectionswerecarried out at 200400 nm, based on the previously obtained calibration curves. The solubility proflile of ciprofloxacin at various pHs mediumshowsintable112. Preparationofcoretablets Core tablets containing 250 mg of ciprofloxacin and superdisintegrant (SD) / osmogen (OM) were prepared with microcrystallinecellulose(Avicel102)asfillerbyawetcompression method using starch paste as a binder. The wet granulation mass waspassedthroughamesh#10anddriedat60Cfor1hinahotair oven.Thedriedgranulesweresizedbypassingthroughasieve#14. These granules were collected and mixed with 5% magnesium stearate and 5% talc. These lubricated granules were compressed into tablets on singlestation tablet punch machine (Modern EngineeringNewDelhi,India)using4mmdeepconcaveand1.2mm round,flatandplainpunches(Table2) Coatingoftablets ThecoatingsolutioncontainingGuargum,XanthangumandPectin intheratioof1:1:2waspreparedinamixtureof1:1ethanol:water mixture using TEC (5% w/v) as plasticizer (Table 3). Gums containing mucilage stirred gently for a period of 10 min with magnetic stirrer. Dispersion was transferred to a filtering flask for air bubble removal by using a vacuum pump after complete homogenization. The core tablets containing ciprofloxacin were coatedatdifferentlevelsofcoatingbyusingspraypancoat(Figure 1).Table4showedalldetailsofthecoatingprocessparametersused for coating on formulation SDCA3. Samples were removed every hourandmean coatingweightgaincalculated.Thecoatingprocess wasrepeateduntilthedesiredlevelcoatingweightwasachieved. After get best result from experimental result given in table 5, coatingofsuchparameterusedforallanotherformulations. Disintegrationtest Disintegration testing of tablets was carried out according to the Indianpharmacopoeia(1885)toidentifytheeffectofdisintegration agentincomparisontotheosmoticagents(suchassodiumchloride and potassium chloride) in carrying out the disintegration. DisintegrationtestingwascarriedoutinphosphatebufferpH6.8. Burstingtime Burstingtimewasdeterminedasthetimenotedvisually,whenthe tablet coat was no longer able to withstand the internal pressure andthetabletopenedup.Thetestwascarriedoutinthedissolution mediabykeepingthetabletsin buffer(pH6.8)at100rpmat37 0.5C.Thetestwascarriedout6tabletsforeachformulation. Invitrodissolutionstudy Invitro dissolution study was performed on the tablets to identify the effects of different coating levels on release profiles of the tablets.Thespraycoateddosageformofciprofloxacinwasevaluated fortheir integrity in thephysiologicalenvironment ofstomachand small intestine under conditions mimicking mouth to colon transit. These studies were carried out using a IP dissolution rate test apparatus (apparatus type II, 50 rpm, 370.5C). The tablets were testedfordrugreleasefor2hin0.1NHcl(900ml)astheaverage gastricemptyingtimeisabout2h.Thenthedissolutionmediumwas replaced with pH 7.4 Sorensons phosphate buffer (900 ml) and testedfordrugreleasefor3hastheaveragesmallintestinaltransit timeisabout3h.Attheendofthetimeperiods,twosampleseachof 1 ml were taken, suitably diluted and analysed for ciprofloxacin content at 269 nm using a double beam UV spectrophotometer (Shimadzu,UV1800). Thesusceptibilityofgumcombinationcoatstotheenzymaticactionof colonicbacteriawasassessedbycontainingdrugreleasestudiesin100 mlpH6.8phosphatebufferedsalinetomaintaincolonicpHcondition.At the end of the time periods, two samples each of 1 ml were taken, suitablydilutedandanalyzedforciprofloxacincontentat271nmusinga doublebeamUVspectrophotometer(Shimadzu,UV1800). Characterizationofreleaseprofile Releaseprofileofnaturalbiodegradablecoatedpolymerscontaining superdisintegratingagentandosmogenstabletswerecharacterized forreleaselagtime(Tlag)andreleaseratek.Releasedatawithinthe linear range were selected and fitted to a zeroorder mathematical model: Q=C+kt Where Q is the release percentage at time t; k is the slope of the fittedlinearequationandhererepresentsreleaserate;andC isthe interceptofthelinearequation.Tlagisdefinedasthetimeofthestart ofciprofloxacinreleaseandcalculatedherefromthefittedequation, settingQ=0: Tlag=C/k. The linearequation is based onregression of at leastthree release data, and only correlation coefficient of over 0.99 is acceptable for Tlagandkcalculation13. RESULTSANDDISCUSSION Disintegrationtestuncoatedtablets Atthehighestlevel,3mgofSDcontainingwithSSG,thedisintegration time was 3.54min in bufferpH 6.8. The result of other formulations (tablets with sod. CMC, SLS), disintegration time was 4.56 min and 4.58min,respectively(Table6).TheresultdepictsthattheSDtablets disintegrate at faster rate than osmogen tablets, once the tablet coat dissolves during invitro release. Disintegration test carried out on coated tablets with lower coating level of 10% showed that disintegration time for tablets was greater than 185 min. This result pass disintegration test as prescribed under Indian pharmacopoeial standardforentericcoatedtablet.Burstingtimesforeachformulation withdifferentlevelsofcoatingaregiveninTable7. InvitrodissolutiontestonSDtablets AlltheformulationmettheUSPcriteriaforentericperformancetestin 0.1N HCl (for 2 hr). In tablets containing 3 mg of superdisintegrant (SDC) coated with 20% coating, SDCA3 tablets, and cumulative percentdrugreleasewas1.95%inthefirst5hofthestudy,andthis increasedto16.78%in6handwas82.22%in12h.Weobservedthat only66.13%drugreleasefromtheformulationtakesplaceinthe612 h intervals. The coating was decreased to 10% in SDCA1.5 tablets. SDCA1.5tabletsshowedacumulativepercentdrugreleaseof1.94% inthefirst5hofthestudy,whichincreasedto11.6%in6hrandwas 93.44%in12h.Weobservedthatonly81.87%drugreleasefromthe formulationtakesplaceinthe612hintervals.Theabovetworesults of SDCA3 and SDCA1.5 indicate that a 3mg content of SD in the tabletshowsthedesiredburstingtime.InSDCA3tablets,nearly16% of drug release is observed between 26 h intervals showing rapid drug release. Similarly in SDCA1.5 tablets this rapid drug release periodwasbetween27h,showingnearly17%drugreleaseinthese 7hintervals.So,thecoatweightwasfurtherincreasedforretardation of release containing 1.5% super disintegrating agent as SSG. The dissolutionprofilesofciprofloxacintabletscontaining3mgofSD(SD CA3,SDCB3,andSDCC3)areshowninFigure2.Resultsshowthat byincreasingthecoatweightto20%inSDCA3,B3andC3tabletsthe rapid release period depend on nature and concentration of various superdisintegratingagentgivenintable2,andtherapidreleasewas seen in 511 h interval with more than 70% drug release in this period.Toreducethecoatweight,theamountofSDinthetabletwas reduced to 1.5 mg. The tablets SDCA1.5 containing 1.5 mg of SD, coatedto10%coatweight,showedacumulativepercentdrugrelease of1.95%inthefirst5hofthestudy,whichincreasedto11.64%in6 hrandwas93.44%in12h.Weobservedthat92%drugreleasesfrom theformulationtakesplaceinthe612hintervals,becausedependon formulation coated with 10% coat weight passage through colonic environment.Thelagtimefordrugreleasefromtheformulationwas= 6h(Figure3). 161

Jainetal. IntJPharmPharmSci,Vol2,Issue4,160165 Table1:ThesolubilityvaluesofciprofloxacinatvariouspHmedium Media Water 0.1NHcl pH4.5 pH6.8 pH7.4 Solubility (mg/ml) 2.323 2.786 0.0121 0.0110 0.1698 Mean 2.348 2.7866 0.126 0.0116 0.1678 Relativestandard deviation% 0.0279 0.0237 0.00045 0.000388 0.0042 Table2:Formulationcodeandthepercentagesuperdisintegratingagent/osmoticagentpresentinthecoretablet Formulationcode %Superdisintegratingagentinthetablet Sodium Sodiumcarboxy Sodiumlauryl starch methylcellulose sulphate glycollate 1.5 1.5 1.5 3 3 3 %ofosmoticagentinthetablet Sodiumchloride Potassiumchloride 92 92 92 92 Standarderrorof Mean(SEM) 0.0114 0.0096 0.000183 0.000158 0.00171 Lower95%confidence interval 2.319 2.762 0.0121 0.011 0.1630 PValue >0.01 >0.01 >0.01 >0.01 >0.01

SDCA1.5 SDCB1.5 SDCC1.5 SDCA3 SDCB3 SDCC3 OMCSC1 OMCKC1 OMCSC2 OMCKC2

SD=superdisintegrant,OM=osmoticagent,KC=potassiumchloride,SC=sodiumchloride.

Table3:Coatingvariablesandcombinationofpolymersandthepercentcoatweight Formulationcode SDCA1.5 SDCB1.5 SDCC1.5 SDCA3 SDCB3 SDCC3 OMCSC1 OMCKC1 OMCSC2 OMCKC2 Thesmallamountofdisintegrantisunabletoexertitseffectwithinthe desiredtime.ConsideringthenormallyacceptedGItransittime,2hfor stomach and 34 h for small intestine, the SDCA1.5 and SDCA3 formulations release the drug directly into colon. The increase in retard time of SDCA3 tablets containing 3 mg of SD was due to increase in coat weight. The disintegration and dissolution time dependsonthecoatingthickness14,aswellastheamountofSDadded. The coat weight of these systems may seem to be very less with compressioncoatedsystems;thecoatweightmaymorethan200%of the core. The present study shows that the dissolution time can be retarded by increasing the coating thickness14 as well as the amount and nature of SD added. The release of drug from the coated tablets canbeattributedtoporeformationandburstingofthecoatduetothe presenceofSD.TheburstingoftabletswithSDoccursbecauseofrapid uptakeofwaterfromthepores,followedbyswellingduetocapillary action15. Crosslinked PVP, when added to the formulation has enhances dissolution of poorly soluble drugs from solid dosage forms16.Thismight have contributedtothe faster dissolution.The r2 value and Tlag time of all formulation containing super disintegrating agentswereshowedintable8. Invitrodissolutiontestonosmogentablets Theformulationwhichcontainingpotassiumchlorideosmogenwitha coat weight of 10%, OMCKC 1 tablets, the cumulative percent drug release was found to be 7.88% in the first 4.45 h of the study and release was too much faster with a total of 96.25% of drug was releasedin12h.Thesesystemsseemquitepromisingforasustained delivery of drug into the colonic region (Figure 4). To refine these systems further, the coat level was increased. When coating was increased from 10 to 20% (OMCKC 2), a cumulative percent drug releaseof6.88%wasfoundinthefirst4.32hofthestudyandshowed bursteffect,thereleaseofdrugincreasedupto94.22%in12h(Figure 5). These resultsmaybeattributedtothefactthatan increase in coat weightledtodecreasedseepingofwaterintothetablet,duetoadelayed poreformationinthickercoats.Thus,thetabletsarenotabletorelease thecompletedrugwithintheusualcolonictransittimeabout18h. Tablets containing sodium chloride (OMCSC 1) coated to 10% showed a cumulative percent drug release of 14.44% in the first 4.38hofthestudy,whichincreasedto99.32%in12h.Weobserved that 83% drug was released from the formulation in the 612h intervals. When coating was increased further from 10 to 20% in OMCSC2tablets,acumulativepercentdrugreleasewas12.44%in thefirst4.40hofthestudyandwas96%in12h.Weobservedthat 82% drug release from the formulation takes place in the 612h interval. The dissolution profiles of ciprofloxacin tablets containing sodiumchloride(OMCSC1andOMCSC2)areshowninFigure4 and 5. This may be explained similarly as in OMKC tablets. Even though sodium chloride has a higher osmotic pressure than potassium chloride, it requires lower percentage of coating for completereleaseofdrug.At16%ofcoating,thereleaseofdrugwas found to be 99.37% in 12h. But after increasing the coat weight to 24%, the release was retard to 96.88% in 12h. The release from sodium chloride tablets was significantly similar but faster as compared with potassium chloride tablets at approximately the same coating level. The release of drug from the tablets containing osmogens is due to development of hydraulic pressure; when dissolution medium imbibe the osmogen, it exerts hydraulic pressureonthefilmandrupturesthecoating.Ther2 valueandTlag timeofallformulation containing super disintegratingagents were alsoshowedintable8. 162 Combinationofpolymers Guargum,XanthangumandPectinintheratioof1:1:2 %coatweight 10 10 10 20 20 20 10 10 20 20

Jainetal. IntJPharmPharmSci,Vol2,Issue4,160165

Fig.1:Fabricatedcoatingpanforcoatingofciprofloxacintablets
100 90
Cummulative percent drug release

80 70 60 50 40 30 20 10 0 0 5
Time (h)
SD-C-A3 SD-C-B3 SD-C-C3

10

15

Fig.2:CummulativepercentdrugreleaseversustimeprofileofSDCA3,SDCB3andSDCC3

120

100

Cummulative percent drug release

80

SD-C-A1.5
60

SD-C-B1.5 SD-C-C1.5

40

20

0 0 2 4 6 8 10 12 14

Time (h)

Fig.3:CumulativepercentdrugreleaseversustimeprofileofSDCA1.5,SDCB1.5andSDCC1.5.

Table4:SelectionoflevelsofindependentvariablesofcoatingparametersforcoatingofpolysaccharidepolymeronSDCA3formulation (weightgain20%) Independentvariables Atomizingpressure(bar) X1,Inlettemperature(C) Bedtemperature(C) X2,Panspeed(rpm) Sprayrate(g/ml) Dryingintheequipmentaftercoating(min) Finaldryinginoven

A 1 40 25 50 10 15 60Cfor1h

Level B 1 50 35 75 10 15 60Cfor1h

Table5:MatrixofexperimentaldesignandresultofstudyofSDCA3formulation Exp. 1 2 3 4

X1 A B A B

X2 B A A B

Tabletthickness Height(cm) Width(cm) 0.60 1.32 0.62 1.41 0.59 1.36 0.62 1.34

Coatingtime(h) 1.46 1.25 1.37 1.31

Hardness 6.2 6.5 5.9 6.4

Drugreleaset50%(h)meanSD& lower95%confidenceinterval 9.160.03533&9.077 9.220.05568&9.032 9.110.0916&8.902 9.010.05033&8.932

163

Jainetal. IntJPharmPharmSci,Vol2,Issue4,160165 Table6:DisintegrationtimeoftabletuncoatedcorestestedinphosphatebufferpH6.8(n=6) Formulation Tabletswith1.5mgofSSGsuperdisintegrant Tabletswith3.0mgofSSGsuperdisintegrant Tabletswith1.5mgofsod.CMCsuperdisintegrant Tabletswith3.0mgofsod.CMCsuperdisintegrant Tabletswith1.5mgofSLSsuperdisintegrant Tabletswith3.0mgofSLSsuperdisintegrant Tabletswithsodiumchloride Tabletswithpotassiumchloride
[

Time(min) 3.13 3.54 4.18 4.56 4.03 4.58 6.54 8.12

Table7:Burstingtimeofvariouscoatedformulations(n=6) Formulationcode SDCA1.5 SDCB1.5 SDCC1.5 SDCA3 SDCB3 SDCC3 OMCSC1 OMCSC2 OMCKC1 OMCKC2

Time(h) 5.02 5.08 5.20 5.05 5.18 5.25 4.38 4.24 4.45 4.32 Table8:Releasecharacteristicsofzeroorderkineticsfittingatdifferentfactorlevels

Factor SSGcontentincoretablet Sod.CMCcontentincoretablet SLScontentincoretablet CoatingweightofSodiumchloridecoretablet CoatingweightofPotasiumchloridecoretablet

Factorlevel 1.5mg 3.0mg 1.5mg 3.0mg 1.5mg 3.0mg 10 20 10 20

Timespan 5.2212 5.2012 5.1212 5.0512 5.0912 5.0112 4.1312 3.4512 4.0512 3.5012

r 0.990 0.990 0.996 0.991 0.990 0.991 0.991 0.991 0.990 0.991

Tlag(h) 4.90 4.31 5.03 4.38 5.16 4.89 3.46 4.08 4.33 4.31

k 13.13 11.95 13.78 11.69 14.33 11.54 12.74 12.58 12.19 12.07

120
Cummulative percent drug release

100 80 60 40 20 0 0 2 4 6 Time (h) 8 10 12 14 OM-C-SC 1 OM-C-KC 1

Fig.4:CumulativepercentdrugreleaseversustimeprofileofOMCSC1andOMCKC1.

120

Cummulative drug release (%)

100 80 60 40 20 0 0 5 10 15
OM OM

Fig.5:CumulativepercentdrugreleaseversustimeprofileofOMCSC2andOMCKC2. 164

Jainetal. IntJPharmPharmSci,Vol2,Issue4,160165 CONCLUSION The presence of superdisintegrant/osmotic agent inside core formed timecontrolled drug delivery systems that could facilitate drugdeliveryintodifferentsegmentsoftheGITdependinguponthe coatweightandtheconcentrationoftheseagents.Fastbursttablets could be formulated making use of SDs rather than osmogens. Presence of 3mg SD in the tablet coated to a coat weight of 20% formed fast release tablets facilitating drug release in the proximal colon. The coat weight determines the silent/lag phase of the formulation,whereasthecoatweightandamountofSDinthetablet determinesthebursteffectandrapid/sustaineddrugrelease. Osmotic tablets could be formulated making use of potassium chloride/sodiumchlorideinthecoretabletsandfurthercoatedwith polysaccharide polymers. A coat weight of 10% in sodium chloride tablets would deliver 83% of the drug into the colonic region in a sustained manner. In potassium chloride tablets, a coat weight of 10% facilitated the delivery of more than 82% of drug into the colonic region. According all the results conclude that the formulation containing superdisintegrating agents showed a best drugdeliverysystemforcolontargeting. REFERENCES 1. 2. 3. 4. LinShu L, Marshall L, Fishman, Kevin B, Hicks M, Kende GR. Pectin/Zein Beads for Potential ColonSpecific Drug Delivery: SynthesisandinVitroEvaluation.DrugDel2006;13:417423. Sarsija S, Hota A. Colon specific drug delivery systems. Ind J PharmSci2000;62:18. LeeVHL.Changingneedsindrugdelivery:PeptideandProtein DrugDelivery,TaylorFrancis,MarcelDekker,NewYork;1991. Ikesue K, Kopeckova P, Kopecek J. Degradation of proteins by enzymesofthegastrointestinaltract.ProcIntSympControlRel BioactMater1991;18:580581. 5. 6. 7. 8. 9. 10. 11. 12. 13. ReddySM, Sinha VR, Reddy DS.Novel oral colonspecific drug delivery systems for pharmacotherapy of peptides and nonpeptidedrugs.DrugToday1999;35:537580. SinhaVR,KumriaR.Bindersforcolonspecificdrugdelivery:an invitroevaluation.IntJPharm2002;249:2331. Hoda AEL. Modulation of a Pulsatile Release Drug Delivery System Using Different Swellable/Rupturable Materials. Drug Del2007;14:539546. Leopold CS. Coated dosage forms for colonspecific drug delivery.PharmSciTechnolToday1999;2:197204. AshfordM,FellJ,AttwoodD.Aninvitroinvestigationintothe suitabilityofpHdependentpolymersforcolonictargeting.IntJ Pharm1993;91:241245. Sinha VR, Kumria R. Coating polymers for colon specific drug delivery:acomparativeinvitroevaluation.ActaPharm2003a; 53:4147. Kinget R, Kalala W, Vervoort L. Colonic drug targeting. J Drug Target1998;6:129149. Fatmanur TD, Fsun A, Sevgi T, Oznur K. Invitro and Invivo EvaluationofMesalazineGuarGumMatrixTabletsforColonic DrugDelivery.JDrugTarget2004;12:105112. Baojian W, Ningyun S, Xiuli W, Wei W. Characterization of 5 Fluorouracil Release from Hydroxypropylmethylcellulose CompressionCoated Tablets. Pharm Dev Technol 2007; 12: 203210. Ashford M, Fell T. Targeting drugs to the colon: delivery systems for oral administration. J Drug Target 1994; 2: 241 258. Kibbe H. Crosspovidone: Handbook of Pharmaceutical Excipients.UnitedKingdom,Washingtion;2000. Kornblum SS, Stoopak SB. A new tabletdisintegrating agent: crosslinked polyvinylpyrrolidone. J Pharm Sci 1973; 62: 43 49.

14. 15. 16.

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