eye drop and ointment.ppt

Opthalmic dosage form

1. Ophthalmic
Products

2. Ophthalmic Products
•OphthalmicProductsarethesterileproducts
meantforinstillationintotheeyeinthespace
betweeneyeleadsandeyeballs.
•Theseproductsmustbesterileandare
preparedunderthesameconditionsand
samemethodsasotherParenteral
preparation.

3. •Definition:Ophthalmicpreparations(eye
preparations)aresterile,liquid,semi-solid,or
solidpreparationsthatmaycontainoneor
moreactivepharmaceuticalingredient
intendedforapplicationtotheconjunctiva,
theconjunctivalsacortheeyelids.
•Theyarespecializeddosageformsdesignedto
beinstilledontotheexternalsurfaceofthe
eye(topical),administeredinside(intraocular)
oradjacent(periocular)totheeyeorusedin
conjunctionwithanophthalmicdevice.

4. •Themostcommonlyemployedophthalmic
dosageformsaresolutions,suspensions,and
ointments.
•Thenewestdosageformsforophthalmicdrug
deliveryare:gels,gel-formingsolutions,ocular
inserts,intravitrealinjectionsandimplants.

5. ADVANTAGE
•Theyareeasilyadministeredbythenurse.
•Theyareeasilyadministeredbythepatient
himself.
•Theyhavethequickabsorptionandeffect.
•Lessvisualandsystemicsideeffects.
•Increasedshelflife.
•Betterpatientcompliance.

6. DISADVANTAGES
•Theveryshorttimethesolutionstaysatthe
eyesurface.
•Itspoorbioavailability.
•Theinstabilityofthedissolveddrug.
•Thenecessityofusingpreservative.

7. Formulation
1)Drug
2)Preservative
3)Sterilization
4) Isotonicity
5)Buffer
6)Viscosity
7)Container
8)Label

8. 1.Drugs-Thesecontainsdrugsofvarious
categoriesincludingantiseptic,anti-
inflammatoryagent,mydriaticormiotic
properties
2.Preservative-Eyedropshouldbesterileand
shouldcontainpreservativestoavoidmicrobial
contaminationwhencontainerisopen.The
preservativeforophthalmicuseincludes
benzalkoniumchloride,chlorbutanol,
phenylmercuricacetate,phenylmercuricnitrate
etc.,

9. 3.Sterilization-Eyedropsaresterilizedby
autoclavingat121°Cfor15minutesorby
bacteriafiltertoavoidthermaldegradationfor
example-preservativechlorbutanolhydrolyzesat
hightemperature
4.Isotonicity-Allthesolutesincludingdrug
contributetotheosmoticpressureoftheeye
drip,thereforeisotonicityoftheformulashould
becalculatedanditisadjustedwithsodium
chloride,forexamplesodiumchloride0.9%and
boricacid1.9&areiso–osmotic.

10. 5.Buffer-thebuffershouldbeaddedto
maintainbalancebetweencomfort,solubility,
stabilityandactivityofdrug.Forexamplethe
hydrolysedchlorbutanolformshydrochloride
acidmakingthedropacidic.Whereascertain
druglikepilocarpinehydrochlorideareacidic.
6.Viscosity-thesizeofthedropandits
residenceineyedependsonviscosityofeye
drops.Methylcellulose,hydroxypropyl
methycelluloseandpolyvenylalcoholare
commonviscosityinhancer.

11. 7.Container-thecommonlyusedcontainerfor
ophthalmicsolutionsorsuspensionismulti-
dosecontainer(5ml,10ml).Glasscontaineris
suppliedwithsterileplasticdropper.Plastic
bottlesarewithbuiltupnozzle.
8.Label-Notforinjection.Forexternaluseonly.
Shakewellbeforeuse.(ifitissuspension)

12. Ophthalmic Products include:
-Eye Drop
-Eye Lotion
-Eye Ointment
-Eye Suspension
-Contact Lens Solution

13. Essential Characteristics of Different
Ophthalmic Preparation
1.ForeignParticles–Alltheophthalmicproductshouldbe
clearandfreefromtheforeignparticles,fibers,and
filaments
2.Viscosity–Inordertoprolongthecontacttimeofthe
drugintheeye,variousthickeningagentsareaddedin
themlikepolyvinylalcohol(1-4%),polyethyleneglycol,
methylcellulose.
TheThickeningagentsmusthavefollowingproperties
-Itshouldbeeasytofilter
-Itshouldbeeasytosterilize
-Itshouldbecompatiblewithotheringredient
-Itshouldpassestheclaritylevel

14. 3.Tonicity–Ophthalmicpreparationsaremustbe
isotonicwithlachrymalsecretionstoavoiddiscomfort
andirritation.1.9%boricacidandsodiumacid
phosphatebufferarecommonlyusedasisotonic
vehicle.
4.pHofthepreparation–pHisplaysveryimp.Rolein
thetherapeuticactivity,solubility,stability,and
comforttothepatients.ThetearshavepHnearabout
7.5.
5.Sterility–Theophthalmicpreparationaremustbe
sterilewhenitprepared.Pseudomonasaeruginosais
verycommongramnegativebacteriawhichgenerally
foundintheophthalmicproductsanditmaybecause
seriousinfectiontothecornea.

15. 6.SurfaceActivity–Thevehiclesareusedinthe
ophthalmicpreparationmusthavegood
wettingabilitytopenetratecorneaandother
tissue.
•TheBenzoalkoniumChloride,Polysorbate20,
Polysorbate80,etcaresomeofsurfactant
whicharecommonlyused.

16. EYE DROPS
•EyeDropsaresterileaqueousoroilysolutions
orsuspensionofdrugthatareinstilledinto
eyewiththehelpofdropper.
•TheEyeDropsareusuallycontaindrugs
havingantiseptic,anesthetic,anti
inflammatory,etc.

17. Disadvantages of eye solutions:
•Theveryshorttimethesolutionstaysatthe
eyesurface.
•Theretentionofasolutionintheeyeis
influencedbyviscosity.
•Itspoorbioavailability(amajorportioni.e.
75%islostvianasolacrimaldrainage).
•Examplesoftopicaleyesolutions:Atropine
sulphateeyedrops.Pilocarpineeyedrops.
Silvernitrateeyedrops.Zincsulphateeye
drops.

18. Essential characteristics of Eye Drops
•Theyshouldbesterile.
•Theyshouldbeiso-osmoticwithlachrymal
secretion.
•Theyshouldbefreefromtheforeignparticles,
fibersandfilaments.
•TheyshouldhavealmostneutralpH.
•Theyshouldbepreservedwithsuitable
bacterioside.
•Theyshouldremainstableduringitsstorage.

19. Adjuvant or Formulating Agents
•ThickeningAgent-MethylCellulose,polyvinylalcohol,
polyethyleneglycoltheseareagentsarecommonly
usedforincreasetheviscosityofeyedrop
•Buffers–BuffersareaddedforthemaintainingpHof
theeyedrop.BoricAcid,SodiumAcidPhosphate,
SodiumCitrateareusedasbufferingagent.
•AntiOxidant–Thesearetheagentsareaddedforthe
preventionofoxidation.Sodiummetabisulphate(0.05
–0.5%)andsodiumthiosulphate(0.1–0.2%)

20. •WettingAgent–Theseagentsareusedfor
properpenetrationofeyedropsintothe
corneaoftheeye.Polysorbate20and
Polysorbate80areusedaswettingagent.
•Isotonicityadjustmentsubstances–Eye
dropsaremadeisotonicwiththelachrymal
secretionwiththehelpofvariousbuffersand
othersolutions.

21. Example of Eye Drop
Rx
AtropineSulphate1g
PhenylMercuricNitrate50.0mlSolution0.002
%
PurifiedWateraddupto100ml
•Direction:Tobeusedasdirectedby
Physicians.

22. Manufacturing Techniques
•Manufacturedbydissolutionoftheactive
ingredientsandaportionoftheexcipientsintoall
portionofwater.
•Thesterilizationofthissolutiondonebyheator
bysterilizingFiltrationthroughsteriledepthor
membranefiltermediaIntoasterilereceptacle.
•Thissterilesolutionisthenmixedwiththe
additionalrequiredSterilecomponentssuchas
viscosity–impartingagents,Preservativesandso
andthesolutionisbroughttofinalVolumewith
additionalsterilewater.

23. Packaging
•Eyedropshavebeenpackagedalmostentirelyin
plasticdropperbottles.
•ThemainadvantageoftheDropperare:
convenienceofusebythepatient
decreasedcontaminationpotential
lowerweight
lowercost
•Theplasticbottleanddispensingtipismadeoflow-
densitypolyethylene(LDPE)resin,whichprovidesthe
necessaryflexibilityandinertness.
•Thecapismadeofharderresinthanthebottle.

24. •Aspecialplasticophthalmicpackagemadeof
polypropyleneisintroduced.
•Thebottleisfilledthensterilizedbysteam
underpressureat121°C.
•Powderforreconstitutionalsouseglass
containers,owingtotheirheat-transfer
characteristics,whicharenecessaryduringthe
freeze-dryingprocesses.

25. •The glass bottle is made sterile by dry-heat or
steam autoclave sterilization.
•Amber glass is used for light-resistance.

26. Eye Ointment
•EyeOintmentaresterilepreparationsmeantfor
applicationtotheeye.
•Thesearepreparedunderasepticconditionsand
packedinsterilecollapsibletubes.
•Example
Rx
YellowSoftParaffin80gm
LiquidParaffin10gm
WoolFat10gm

27. •OintmentsOphthalmicointmentsmustbesterile.
•Theointmentbaseselectedforanophthalmic
ointmentmustbenonirritatingtotheeyeand
mustpermitthediffusionoftheactiveingredient
throughoutthesecretionsbathingtheeye.
•Ophthalmicointmentshavealongerocular
contacttimewhencomparedtomany
ophthalmicsolutions.
•Onedisadvantagetoophthalmicointmentsisthe
blurredvisionthatoccursastheointmentbase
meltsandisspreadacrossthelens.

28. Manufacturing Techniques
•Ophthalmicointment:Theointmentbaseissterilized
byheatandappropriatelyfilteredwhilemoltento
removeforeignparticulatematter.
•Itisthenplacedintoasterilesteamjacketkettleto
maintaintheointmentinamoltenstateunderaseptic
conditions,andthepreviouslysterilizedactive
ingredient(s)andexcipientsareaddedaseptically.
•Theentireointmentmaybepassedthrougha
previouslysterilizedcolloidmillforadequate
dispersionoftheinsolublecomponents.
•Aftertheproductiscompoundedinanasepticmanner
,itisfilledintoapreviouslysterilizedcontainer.

29. Examples
•Chloramphenicol ointment.
•Tetracycline ointment.
•Hydrocortisone ointment.

30. Packaging
Ophthalmicointmentarepackagedin:
1.Smallcollapsibletintubeusuallyholding3.5g
ofproduct.thepuretintubeiscompatible
withawiderangeofdrugsinpetrolatum-
basedointments.
2.Aluminumtubeshavebeenusedbecauseof
theirlowercost

31. 3.PlastictubesmadefromflexibleLDPEresins
havealsobeenconsideredasanalternative
material.Filledtubesmaybetestedfor
leakers.
4.Thescrewcapismadeofpolyethyleneor
polypropylene.
5.Thetubecanbeasourceofmetalparticles
andmustbecleanedcarefullybefore
sterilization(byautoclavingorethyleneoxide).

32. Evaluation of Ophthalmic
preparations
Metal Particles:
•Thistestisrequiredonlyforophthalmic
ointments.
•Thepresenceofmetalparticleswillirritatethe
cornealorconjunctivalsurfacesoftheeye.
•Itisperformedusing10ointmenttubes.
•Thecontentfromeachtubeiscompletely
removedontoaclean60-mm-diameter
Petridishwhichpossessesaflatbottom

33. •Thelidisclosedandtheproductisheatedat
85°Cfor2h.
•Oncetheproductismeltedanddistributed
uniformly,itiscooledtoroomtemperature.
•Thelidisremovedaftersolidification.
•Thebottomsurfaceisthenviewedthroughan
opticalmicroscopeat30×magnification.

34. •Theviewingsurfaceisilluminatedusingan
externallightsourcepositionedat45°onthe
top.
•Theentirebottomsurfaceoftheointmentis
examined,Andthenumberofparticles50μmor
abovearecountedusingacalibratedeyepiece
micrometer.
•TheUSPrecommendsthatthenumberofsuch
particlesin10tubesshouldnotexceed50,with
notmorethan8particlesinanyindividualtube.

35. •Limitsarenotmet,thetestisrepeatedwith
anadditional20tubes.
•Inthiscase,thetotalnumberofparticlesin30
tubesshouldnotexceed150,andnotmore
than3tubesareallowedtocontainmorethan
8particles.

36. Leakage test
•Thistestismandatoryforophthalmic
ointments,whichevaluatestheintactnessof
theointmenttubeanditsseal.
•Tensealedcontainersareselected,andtheir
exteriorsurfacesarecleaned.
•Theyarehorizontallyplacedoverabsorbent
blottingpaper.
•Maintainedat60±3°Cfor8h.

37. •Thetestpassesifleakageisnotobservedfrom
anytube.
•Ifleakageisobserved,thetestisrepeated
withanadditional20tubes.
•Thetestpassesifnotmorethan1tubeshows
leakageoutof30tubes.

38. Sterility Tests
•Ophthalmicsemisolidsshouldbefreefrom
anaerobicandaerobicbacteriaandfungi.
•Sterilitytestsarethereforeperformedbythe:
1.Membranefiltrationtechnique.
2.Direct-inoculationtechniques.

39. •IntheMembranefiltrationmethod:
•Asolutionoftestproduct(1%)ispreparedin
isopropylmyristateandallowedtopenetrate
throughcellulosenitratefilterwithporesize
lessthan0.45μm.
•Ifnecessary,gradualsuctionorpressureis
appliedtoaidfiltration.

40. •Themembraneisthenwashedthreetimes
with100-mLquantitiesofsteriledilutingand
rinsingfluidandtransferredasepticallyinto
fluidthioglycolate(FTG)andsoybean–casein
digestmedium(SBCD).
•Themembraneisfinallyincubatedfor14days.
•GrowthonFTGmediumindicatesthe
presenceofanaerobicbacteria.

41. •Soybean casein digest medium indicates fungi
and aerobic bacteria.
•Absence of any growth in both these media
establishes the sterility of the product.

42. •IntheDirect-inoculationtechnique:
1partoftheproductisdilutedwith10parts
ofsteriledilutingandrinsingfluidwiththe
helpofanemulsifyingagent.
IncubatedinFluidthioglycolate(FTG)and
soybean–caseindigestmedium(SBCD)media
for14days.

43. •Inbothtechniques,thenumberoftestarticles
isbasedonthebatchsizeoftheproduct.
•Ifthebatchsizeislessthan200the
containers,either5%ofthecontainersor2
containers(whicheverisgreater)areused.
•Ifthebatchsizeismorethan200,10
containersareusedforsterilitytesting.

44. Thank you