ReviewArticle

ROLEOFTASTEANDTASTEMASKINGOFBITTERDRUGSINPHARMACEUTICALINDUSTRIESANOVERVIEW

VIJAYSHARMA1,HIMANSHUCHOPRA2

FacultyofPharmacy,P.R.C.,PristUniversityThanjavur614904(T.N.)India,DepartmentofPharmacy,G.R.D.(P.G.)I.M.T.Deharadun(U.K.)Email:vijaysrampur@gmail.com

Received:07Jun2010,RevisedandAccepted:08July2010

ABSTRACTS

Acceptabilityofanydrugdosageformmainlydependsoveritstastei.e.mouthfeel.drugmoleculeinteractswithtastereceptoronthetonguetogivebitter, sweetorother taste sensation,when theydissolve in saliva.This sensationof taste is the result of signal transduction from the receptororgans for taste, commonlyknownas tastebuds.Nowadaysmostof thepotentdrugs thatmaybe cardiac , analgesics, anti inflammatory, antitubercular, anthalmentics , antibacterial ,anticoagulants, anti epileptics, antimalarials, anti neoplastics, anti thyroids, antiprotozoal, diuretics,histamine receptor antagonists, nutritional agents, opioids analgesics, oral vaccines and sex hormones , most of them are bitter in taste. So itbecomesnecessarytodevelopsuchadosageforthatmustbeacceptableintastetopatientespeciallyincaseofchildrenorgeriatrics.

Toovercomethisproblemsomanytechniquesareavailabletomaskthebittertasteofdrugs.Thesetechniquesarenotonlyservesastomaskthetasteofdrugaswellastoenhancethebioavailabilityofdrugdosageform.Commonlyusedtechniquesthatareadoptedforlargescaleproductionofpharmaceutical dosage formare use of flavors, coating of drug particlewith inertmaterials, by formation of inclusion complexes, byMolecularcomplexesofdrugwithotherchemicals,Microencapsulation,MultipleEmulsions,Prodrugs,usingliposomes,DispersioncoatingandIonExchangeResinapproach.

Keywords:Taste,Tastebuds,TasteMasking,Drugs,andPolymers.

INTRODUCTION

Wheneverwe join somebodyondining table and thosebodies askabout the taste of any food, that timewe told any one out of fourtastethatmaybesweet,sour,bitterorsalty.Althoughitisamatterof dispute over the type of taste but generally these four areconsideredmost.Nowpointisthathowwejustifyaboutthetasteofanyfood.Thisallisdonebyourtongue.Ourtonguehavingsomanycell locatedover it thathelps in justifying the taste, calledas tastebuds.In1908JapaneseresearcherKIKUAEIKEDAfoundanewfifthtasteinglutamatethatiscalledUMAMI,meanmeaty.14

TASTEBUDS

Tastebudsaresmallsenseorgan inmostvertebrates,helps in thedetection of taste. Hence a group of cells, found especially on thetongueTastebudshavebeenidentifiedonthesoftpalate,pharynx,epiglottis,whichallowsdifferenttypesoftastetoberecognized,1

Saltytaste(edge,upperportion)

Thesaltytasteisoneamongthefourtastereceptorsoftongue.Theyarelocatedontheedgeandupperfrontportionofthetongue.12

Sweettaste(tip)

Thesweettasteisoneamongthefourtastereceptorsinthetongue.Theyarefoundonthetipofthetongue.12

Sourtaste(alongsidesinback)

Thesourtaste isalsooneof the fourtastereceptorsof thetongue.Theyoccuratsidesofthetongueandarestimulatedmainlybyacids.12

Bittertaste(back)

Thebittertasteisthelastandoneofthefourtastereceptorsinthetongue. That is located toward the back of the tongue. It isstimulated by a variety of chemical substances,most ofwhich areorganic compounds, although some inorganic compounds such asmagnesiumandcalciumalsoproducebittersensations.12

Workingoftastebuds14

Tastebudsworksby transmitting informationaboutdifferentkindoftastetobrainvianervefibers.Tastebudsforallfourtypeoftaste

i.e.sweet,sour,saltyandbittershowsdistinctdistributionpatternsonthesurfaceofhumantongueTastebudshavebeenidentifiedonthe soft palate, pharynx, epiglottis e. The tongue, soft palate andepiglottis consists of taste buds, that allow human to recognizedifferent tastes in food a they eat. The taste buds are chemoreceptor,meaning that they transmit chemical signals in food intoelectrical signals. These signals travel to the brain via nervoussystemtoexperiencesensationoftaste.

It is to be noted that taste buds in fishes are distributed over theentire surface of the body to provide information aboutsurroundings.14

Effectofageontastebuds5

Cellsthatmakeupthetastebudswithagewearout,asaresulttastebudsbegintodisappearfromroofandthesidesofthemouthexcepttaste buds thats are located over tongue. Remaining taste budsbecomes less sensitive. Researches have been proved that thatsmockingandeatingofscaldingfoodmaydamagetotastebuds.Thislackingoftastemayleadtolossofappetiteandpoornutrition.

Taste is a type of medium to experience the world of tastes forinfants and young children. It is seen that children are moresensitive to certain taste thananyadults. but because taste canbesubjective.themechanismthatcausestastesensitivityinyoungsterscanbedifficulttoanalyze.

Causesofinfectedtastebuds

Taste buds infection usually occurs due to vitamin B complexdeficiency, longterm antibiotics drug therapy following radiation,smoking, vigorous rubbing by a rough tooth and thickening oftissues in elderly and fungal infection (oral thrush) in those withdecreasedimmunity.14

Methodstotesttastebuds67

Toconductthisexperimentwerequiresfollowings

*Foodcolor

Procedure

1. Withhelpofcottonputfoodcolorovertipofyourtongue2. Putreinforcementringovertongue.

International Journal of Pharmacy and Pharmaceutical Sciences

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

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3. Startcountingofpinkdotsinsidetheringbyusingmagnifyingglass.

Thesepinkdotsarefungi formpapillae.Thesearehavingpropertyof not to take up the food coloring. These papillae are tiny bumpslike on our tongue i.e. house your taste budsmore the number ofpapillaemeansmorethesensitivityagainstthetaste. Ifanypersonhaving less than 15 papillae on average called as non tasterwhilethosehavingmorethan30calledassupertaster,67

Pharmaceutical approaches used to mask the taste of bitterdrugs

Useofflavoursandsweetners89

Materials available for tastemaskingcanbeclassifiedaccording tobasictastethat istobemasked.Flavoringagentscanbenaturalor

synthetic in nature.Natural flavors are as Peppermint, Lemon oil;Clove, Balsam, funnel and other distilled fractions. These areavailable as concentrated extracts, alcoholic or aqueous solutions,syrups or spirit.many compositions show effective tastemaskingabilitieswith improved flavor like alkaline earth oxide, an alkalinehydroxide or alkaline earth hydroxide Another compositionconsisting phosphorylated amino acid such as phosphotyrosine,phosphoserine,andphosphothreonineandmixtures.Anetholeistheflavoreffectivelymaskedbittertasteaswellastheaftertasteofzinc,whichisuseintreatmentofthecommoncold.8

Clove oil and calcium carbonate found to be useful to mask theunpalatable active drugs in formulationswhich are intended to bechewedorinformulationofmouthdissolvingtablet.Aspartameandsodiumsaccharinearethesweetenersusedtomaskthebittertasteofdrugs.9

Table1

S.No. Author Drug Flavor Result1. GohelM,10 Nimesulide Camphor Camphorsignificantlymaskedthetasteoftabletwith

sufficientstrength,friability,disintegrationanddissolution.2. Dandagi11 Ofloxacin Aspartame Aspartamesignificantlymaskedthetasteoftablet

Coatingofdrugsusingasuitablepolymer

ByCoatingoneavoidthecontactofbitterdrugbypreventingreleaseofbitterdruginoralcavity.Properselectionofcoatingmaterialwillmasktasteofbitterdrugcompletelywithoutaffectingdrugreleaseprofile.Tastemaskingofibuprofendonebyusingtheairsuspensioncoating technique to form microcapsules, which comprises apharmaceuticalcoreofacrystallineibuprofenandmethacrylicacidcopolymer coating that helps in formulation of chewable tastemaskedtablet.Coatingagentsareusedforcoatingdrugparticleslikestarch; povidone, gelatin,methylcellulose, ethyl cellulose, hydroxylpropylmethylcellulose.etc.12

Shellac is a natural polymer, which is used as enteric coatingmaterial in pharmaceutical applications, provide moisture

protectiveandtastemaskingcoating.13Coatingofdrug,isdonebydissolvingordispersingapolymer in a solvent or bydissolvingordispersingadruginthesolventtoformacoatingsolution;disposingthecoatingsolution.14

Now a day in most of industries coating is being done by usingfluidizedbedprocessor.Inthisapproachdrugpowder(50mfine),arefluidizedinexpansionchamber.Coatingsolutionissprayedwithhelpofspraynozzle.

These coated granules are dried with warm air.Film coating ofsmall granules is technically very difficult, even when a largedose of the drug is required whereas large granules indispersible ormouthdissolving tablets causea gritty texture inthemouth.13

Table2

S.No. Author Drug Polymer Result1. Hiroya

Sugao,12Indeloxazinehydrochloride

mixturecomprisinghydrogenatedoilandsurfactants

PowdersofIndeloxazinehydrochloridewithoutthisbittertaste,microparticles(mediandiameter,130 m)ofIDXwerecoatedtomaskthetaste.

2. Shirai15 Sparfloxacin Lowsubstitutedhydroxypropylcellulose,ethylcellulose

DegreeofTastemaskingincreasesbyethylcelluloseAndHPMCratio.CompletetastemaskingwasdoneEC:HPMC(4/2)

Tastemaskingbyspraydryingtechnique

In the present investigation, bitter taste of drug is masked bypreparingmicroparticlesofdrugwithcertainhydrophilicpolymerssuch as Hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone(PVP)byusingspraydryingtechnique.16Thepurposeofthis technique is to develop the tastemasked microspheres of

intenselybitterdrugbyspraydryingtechnique.Byuseofdifferentpolymers microspheres are formed and it is found that tastemasking capacity and drug release profile was excellent. Themicrospheres were characterized by Fourier transform infraredspectroscopy, scanning electronmicroscopy, Drug loading, in vitrobittertasteevaluation,anddrugreleaseproperties.17

Table3

S.No. Author Drug Polymer Result1. GedamS.S16 Diphenhydramine hydroxypropylmethylcellulose,

PolyvinylpyrrolidoneTastemaskedbypreparingmicroparticlesofdrugwithcertainhydrophilicpolymers.

2. ShreenivasS.A.,18

Ondensetronhydrochloride

Chitosan,MethocelE15LV,andEudragitE100

Tastemaskedmicrospheresofintenselybitterdrugondensetronhydrochloride(OSH)withcompletetastemasking.

3. Shirai19 Sparfloxacin Lowsubstitutedhydroxypropylcellulose,ethylcellulose

DegreeofTastemaskingincreasesbyethylcelluloseAndHPMC.CompletetastemaskingwasdoneEC:HPMC(4/2)

Complexformationwithionexchangeresin

Anotherapproachindevelopmentof tastemasking isbasedonionexchangeresinusedforlargescaleproduction.Ionexchangeresinsare solid and insoluble high molecular weight poly electrolytes.These ion exchange resins can change their mobile ions of equal

charge with surrounding media. The resulting ion exchange isreversibleandstechiometricwithdisplacementofoneionicspeciesbyanother.20

Resin like Tulsion 335 (Polacrilex), indion204 &234 found as acommercialresinfortastemaskingofseveraldrugs.Indion204and

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234 are weak cation exchange resin, used for taste masking ofnorfloxacinandciprofloxacinrespectively.Tulsion335isbeingusedfor preparation of nicotine polacrilex and vit B12 loading/stabilization.21

Strongcationexchangeresin(viz.AmberliteIRP69)arebeingusedto improve the physicochemical properties of ranitidine

hydrochloride such as taste and bulk properties and to sustaindissolution rate.As these are high molecular weight and waterinsoluble resins are not absorbed by the body and are inert innature.Theadsorptionofbitterdrugsonto synthetic ionexchangeresin like amberlite CG 50was used for taste masking ofpseudoephedrineinthechewabledecongestanttablet.22

Table4

S.No. Author Drug Ionexchangeresin

Result

1. Madgulkar,A.R..23

TramadolHCl Tulsion335 Tastemaskedtabletformulatedofsignificantmechanicalstrengththatshowedfastdisintegration.

2.

RaoC.G.G.,24 Quininesulphate Indion234 Thetastemaskedsuspensiononreleasestudiesshowedcompletedrugreleasewithin20min.

3. Bhise25

DiphenhydramineHydrochloride

Indion234 Tastemaskedtabletwasformulatedwithsufficientstrength,friability,disintegrationanddissolution.

4. Cotteril26 Levamisole AmberliteIRP69 LevamisoleAmberliteIRP69resinatetabletwasstableinmouthandreleasedruginacidicenvironmentofstomach(93%).

5. Bhelekar27 RanitidineHCl Indion234 StableRanitidineHClIndioncomplexshowseffectivedrugloadingatdrugresinratio1:1.5andtemperaturedidnotaffectthecomplexationprocess.

6. PisalS.28 Ciprofloxacin Indion234 Thetastemaskedtabletonreleasestudiesshowedcompletedrugreleasewithin30min.

Byinclusioncomplexformation

Cyclodextrin is most commonly used complexing agent as well aschannelingagentto forminclusioncomplex formation forthetastemaskingofbittertasteofthedrugseitherbydecreasingitssolubilityorbydecreasingexposureofdrugparticletotastebudsthere.29

Bitter Taste of ibuprofen has been effectively masked bycyclodextrin.Methodsthatsareusedtomakeinclusioncomplexareas Grinding, Solid dispersion / co evaporated dispersion,Neutralizationmethod,Kneadingmethod,Precipitationmethod,Spraydrying,FreezedryingandMelting.30

Table5

S.No. Author Drug Polymer Result

1. SanghaviN.M.31 Terfenadine Bcyclodextrin Apalatablesyrupofterfenadinecyclodextrincomplexwasformulated.

Byformingsoliddispersion

Soliddispersiondefinedasdispersionofmoreactiveingredientsinan inert carrierormatrixat solid statepreparedby fusion solvent

method. Solid dispersion can also be prepared by coprecipitatemethod for that preparation obtained by solvent method such ascoprecipitate of sulphasalazine and povidone. In this insolublematricesorblendmatricesmaybeusedtomaskthetasteofdrugs.32

Table6

S.No. Author Drug Polymer Result

1. ShahT.J.33 Rofecoxib(RXB) Poloxamer188 ThemeltingmethodwasusedtopreparesoliddispersionsandMDTwasformulated.

2. PunitShah.34 Artemether MonoAminoGlycyrrhyzinatePentahydrate(GLY)

Resultsconclusivelydemonstratedsuccessfulmaskingoftasteandrapiddisintegrationoftheformulatedtabletsintheoralcavitywithimproveddissolution.

Microencapsulationtechnique

Microencapsulationisaprocessofapplyingrelativelythincoatingtosmallparticlesofsolid,dropletsofliquidanddispersion.ThisisthemethodbeingwidelyusedinPharmaindustriestomaskthattasteofbitter drugs as well as bioavailability.Coating agents employed inmicroencapsulation are gelatin, povidone HPMC, ethylcellulose,carnaubawax,acrylicsandshellac.35

In this method bitter drugs are first encapsulated to give freeflowingmicrocapsuleswhicharethenblendedwithexcipientsandcompressed into tablet.Methods used to preparemicroencapsulesareairsuspension,coacervation,phaseseparation,spraydryingandcogeling, pan coating, solvent evaporation and multiorificecentrifugationmethod.36

Table7

S.No. Author Drug Polymer Result

1. Alomran37 Diclofenacsodium Ethylcellulose,Diethylphthalateandpolyethyleneglycol

Theoptimumsolvent,andnonsolventratiorequiredformicroencapsulationwas1;2.Tastemaskingwasaffectedbymicrocapsulecore:wallratiom,presenceofadditiveandconcentrationofplasticizer.

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Bymultipleemusionpreparation

This is the novel technique used tomask the taste of bitter drugs.Multipleemulsionscanbepreparedbydissolvingdrugintheinner

aqueous phase of w/o/w emulsion under condition of good shelfstability. So that release of drug through oil phase takes place ingastrointestinalmedia.36

Table8

Sno. Author Drug Polymer Result1. T.Uchida 38 Polylacticacid NaCl,CaCl2,

BrilliantbluedyeThesepreparedwiththesmallestinternaldropletvolume(63l),theinitialburstreleasewasreducedsignificantly,and50%(w/w)oftheloadedBBremainedinthemicrospheresfor7days.

Byliposomeformation

This is another way of masking the unpleasant taste of bittertherapeuticdrugs.byincorporatingthemintoliposomalformulation

prepared fromeggphosphatidyl cholinemasked thebitter taste ofchloroquine phosphate in HEPES(N2 hydroxyethylpiperzineN2ethanesulfonicacid)bufferatpH7.2.

Table9

S.No. Author Drug Polymer Result1. WienT.39 Quinine,

denatortiumandpropranolol

lipoproteincomposedofphosphatidicacid(PA)andlactoglobulin(LG)

Thesepreparedwiththesmallestinternaldropletvolume(63l),theinitialburstreleasewasreducedsignificantly,and50%(w/w)oftheloadedBBremainedinthemicrospheresfor7days.

Prodrugapproach40

Prodrugs are the chemically modified form of an active drugwhich on biotransformation gives active parent drug when

administered; generally these are the ester form of active druge.g.

Table10

Sr.no. Parentdrug Prodrugwithimprovedtaste1 Triamcinolone Diacetateester2 Clindamycin Palmitateester3 Chloramphenicols Palmitateester

CONCLUSION

Taste masking of bitter drug is common in pharmaceuticalindustriestodevelopadesiredpalatableandtoenhancetheonsetofactionaswellasbioavailabilityofdrug.Soalltheaboveapproachesnot only being used tomask the bitter taste of drug aswell as toenhance the solubility, onset of action aswell as bioavailability ofdrugeitherbyanyoneofabovementionedmethods.

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