ocular drug

1. SEMINAR ON
Ocular Drug Delivery System
PRESENTED BY:
MR. SURDAS RATHWA
M.PHARM (1ST YEAR)
DEPARTMENT OF PHARMACEUTICS
GUIDED BY:
Dr. BHAVESH AKBARI (M.PHARM, PH.D)
DEPARTMENT OF PHARMACEUTICS

2. CONTENT
 Introduction
 Anatomy of eye
 Composition of eye
 Mechanism of ocular absorption
 General pathway for ocular absorption
 Formulation of ocular drug delivery system
 Formulation of ophthalmic preparations
 Marketed formulation
 Evaluation of OCDDS
 Advantages & disadvantages
 References

3. Introduction
 Ocular administration of drug is primarily associated with the need to treat
ophthalmic deseases.
 E.g. Glaucoma , hypoplasia , cataract , anophthalmos , microphthalmos
• Major class of drugs are ;
Miotics : cholinergic agent
Mydriatics: Anti-cholinergics (atropine)
Anti- inflammatory
Anti- infectives
• These drugs are meant for local therapy not for systemic action.

4. Anatomy of eye

5. Anatomy of eye
 The eye is composed of two segments:
1. Anterior segment: It consist of front one-thired part of eye that mainly included
pupil,cornea,iris,ciliary body, aqueous humor and lens.
2. Posterior segment: It consist of back two-thired part of eye that include vitreous humor ,
choroid , retina macula and optic nerve.
 Human eye:
• Diameter 23 mm
• Structure comprise three layers;
1. Outermost layer: The clear transparent cornea and white opaque sclera.
2. Middle layer: The iris anteriorly , choroid posteriorly and ciliary body is intermediate part.
3. Inner layer: Retina

6. Con…
 Cornea
• Epithelium-stroma-endothelium
• Penetration of drug are depends on oil-water partition coefficient.
 Fluid system in eye
1. Aqueous humor: Secreted from blood through epithelium of ciliary body.
2. Vitreous humor: Secreted from blood through epithelium of ciliary body and
diffused through the vitreous body.
 Lachrymal gland
• Secrete tear and wash foreign bodies.
• Moisten the cornea from drying out.

7. Composition of eye
 Water : 98%
 Solids: 1.8%
 Organic elements- protein: 0.67%
 Sugar: 0.65%
 Nacl: 0.66%
 Other mineral elements sodium potassium and amonium: 0.79%

8. Mechanism of ocular absorption
Non- corneal absorption:
 Penetration of drug is across sclera & conjuctiva in intra ocular tissues.
 Non productive: because of penetrated drug is absorbed by general
circulation.
Corneal absorption:
 Outer epithelium: they are rate limiting barrier with pore size is 60A which
are only access small ionic and lipophilic molecules.
 Trans cellular transport: transport between corneal epithelium and stroma.

9. General path way for ocular absorption

10. Formulation of ocular drug delivery system
Dosage form Advantages Disadvantages
Solutions Convenience Rapid precorneal elimination, loss
of drug by drainage, non sustain
action.
Suspension Blurred vision , patient non
compliance.
Drug properties decide
performance loss of both solution
and suspended solids.
Emulsion Prolonged release of drug from
vehicles.

11. Fluoroquinolone are used in ophthalmic delivery
Ant biotic generation Example Activity
1st generation Naladixic acid • Limited activity against gram
negative & gram positive
organism
2nd generation Oxalinic acid
Cinoxacine
Pipemic acid
• Improvement in gram negative
,anti pseudomonal activity.
• Shows limited activity against
gram positive organism.
3rd generation Norfloxacin
Ciprofloxacin
Levofloxacin
Ofloxacin
• Anti pseudomonal activity against
gram negative bacilli.
4th generation Ciprofloxacin
Moxifloxacin
Gatifloxacin
• Dual mechanism of action in
gram negative organism in
addition reducing efflux from the
bacterial cell.
• Improved spectrum of activity.

12. Ophthalmic preparations
• Ophthalmic preparation are sterile products that are intended to be applied
topically to cornea instilled space between eyeball and lower eyelid.
Conventional ocular formulation:
 Suspensions
 Solutions
 Ointment
 Gel
 Emulsions

13. Cont.…
Solutions:
 Dilute with tear and wash away through lacrimal apparatus.
 Usually do not interfere with vision of patients.
 To be administered at frequent interval.
 E.g. Brimo
Suspensions :
 Irritation potential due to the particle size of the drug.
 Longer contact time.
 E.g. Prednisolone acetate suspension
Ointment:
 Longer contact time and greater storage stability.
 Producing film over the eye and blurring vision.
 Interfere with attachment of new corneal epithelial cell to there normal
base.

14. Marketed formulation
• Simbrinza :
It is first combination eye drops which containing carbonic
anhydrous inhibitors and alpha2 agonist for the treatment of
glaucoma.

15. Cont…
• Taptiqom:
 It is fixed dose combination of prostaglandin analogue tafluprost and beta
blocker timolol for the treatment of glaucoma.

16. Marketed products
Brand name Drug Dosage form Use
DICHOL Carbachol Sterile solution and
prefield syringe
Use in ophthalmic
surgery
REFRESH TEARES Hydroxypropyle
methylcellulose
Drops Eye lubricants and
dryness of eye
CELTEAR/
VISCOTEAR
Corbomer Bioadhesive gel Treatment of burning of
eye
TIMOLOL XE Timolol maleate In situ gel Keratocunctivitis
PRED
FORTE
Prednisolone acetate Suspension Anti-allergic and anti-
inflamatories
ACIVIR EYE Acyclovir Ointment Anti-infective
RESTASIS Cyclosporine Emulsion Chronic dry eye diseases

17. Cont...

18. Control drug delivery system
 Implants
• Implant have been widely use in extended the release of drug in ocular fluid
and tissues particularly in posterior segments.
• Implant can be broadly classified in to two categories based on their
degradation properties.
1. Biodegradable
2. Non biodegradable
• Implant can be solid , semisolid , or particulate-based delivery system.

19. Cont..
• For chronic ocular diseases like cytomegalo virus (CMV) in implants are
effective drug delivery system, earlier non biodegradable polymer were used
but they are needed for surgical procedure for insertion and removal.
• Presently biodegradable polymer such as poly lactic acid (PLA) are safe and
effective to delivery drug in to vitreous cavity and show no toxic sing.

20. Iontophoresis
• In iotophoresis direct current devices ions in to cells or tissues.
• If the drug molecule carry positive charge they are driven into the tissues at
the anode ,if negative charged at the cathode.
• Requires mild electric current which is applied to enhance the ionized drug
into tissues.
• Ocular iontophoresis is a drug delivery system is fast , painless , safe and
result in the delivery in high concentration of drug to a specific site.

21. Cont…
• Iontophoresis is useful for the treatment of
bacterial keratitis.

22. Microemulsion
• Microemulsion is dispersion of water and oil solubilized using surfactant and
co-surfactant to reduced interfacial tension and usually characterised by small
droplet size (100nm) higher thermodynamically stability and clear
appearance.
• Selection of aqueous phase organic phase and surfactant co-surfactant system
are critical parameter which can affect stability of system.

23. Nanosuspension
• Nanosuspension have emerged as promising strategies of for the sufficient
delivery of hydrophobic drugs because they enhanced not only the rate and
extend of ophthalmic drug absorption but also the intensity of drug action
with significant extended duration of drug effects.
• For commercial preparation f nanosuspension technique like media milling
and high pressure homogenization have been used.

24. I-VATION
• This are the solid triamicilone acetnoide implant , can delivered up to 24
months.

25. Ocular inserts

26. Nonerodible inserts
 Ocuserts
• The ocusert therapeutic system is flat , flexible , elliptical devises designed to
the place between the sclera and eyelid and to release pilocarpine
continuously steady rate for 7 days.
• The system is consist of three layers:
 Outer layer
 Inner layer
 A retaining ring

27. Erodible inserts
• The solid inserts absorbed in aqueous tear fluid and gradually erode or
disintegrate. The drug is slowly reached from the hydrophilic matrix
• They rapidly loss the solid integrity.
 Three types:
1. Lacriserts
2. SODI
3. Minidisc

28. Lacriserts
• It is sterile rod shape devices made up of hydroxyl methyl cellulose without
any preservatives.
• For treatment of dry eye syndrome.

29. SODI
• It is sterile thin film of oval shape.
• Weight 15-16 mg.
• Used in glaucoma.

30. Minidisc
• Counter disc with a convex front and concave back surface.
• Diameter 4-5 mm.
 Composition
• Silicone based prepolymer
• M-methyle cryloxy butyl functionalities.
• Pilocarpine , chloramphenicol

31. Evaluation of OCDDS
 Thickness of the film:
• Measured by dial caliper at different point and the mean value is calculate.
 Drug content uniformity:
• The cast film cut at different places and tested for drug as per monograph.
 Uniformity of weight:
• Three patches are weighed.

32. Cont….
Percentage moisture absorption:
• In that ocular film are weighed and place in dessicator containing 100ml of
saturated solution of aluminum cloride at 73.5% humidity was maintained.
• After 3 days the ocular film are reweighed and the percentage moisture is
absorbed is calculated using the formula:-
% Moisture absorbed= final weight – initial weight x 100
initial weight

33. Cont….
Percentage moisture loss:
• Ocular film are weighed and kept in a dessicator containg anhydrous calcium
chloride.
• After 3 days these film are reweighed and the percentage moisture loss is
calculated using formula:-
% Moisture loss= initial weight – final weight x 100
initial weight

34. In- vitro evaluation method
 Bottle method:
• In this method drug are placed in bottle containing dissolution medium
maintained at specified temperature and PH.
• Then bottle is shaken.
• A sample of medium is taken out at appropriate intervals and analyzed for the
drug content.

35. Cont…
 Diffusion method:
• Drug solution is placed on the donor compartment and buffer medium is
placed between donor and receptor compartment.
• Drug diffused in receptor compartment is measured at various time intervals.

36. Cont…
 Rotating basket method:
• In this method the dosage form are placed in basket assembly
which connected with the stirrer.
• The basket is lower in to the jacketed beaker containing in to the
buffer medium and temperature at 37 degree centigrade.
• Sample is taken appropriate time interval and analyzed for drug
content.

37. Advantages
• Increase ocular residence, hence improving bioavailability.
• Improving prolonged drug realse and thus better efficacy.
• Increase self life with respect to aqueous solution.
• Reduction of systemic side effect thus reduced adverse effects in case of
topical application.
• Reduction of number of doses administration and thus better patient
compliance.

38. Disadvantages
• Insertion technique is difficult & expulsion of shield may occur
not individually for for each patient.
• Difficult to handle foreign body sensation.
• Occasional loss during sleep or while rubbing eye.
• Interference with vision.
• Difficulty in placement and removal.

39. References
1) https://www.ncbi.nlm.nih.govt/pubmed/19552545
2) Advances controlled and novel drug delivery,CBS publication, N.K Jain,
page no: 219-223.
3) Chein Y.W , Novel drug delivery system, 2nd edition , page no: 269-320.
4) http://youtube.com , EndoSert MDEA Finalist 2012- youtube.flv.
5) www.slideshare.com .
6) Ocular drug delivery system ; an overview, ashim k mitra, world j
pharmacol, June 2013,page no: 47-64.
7) International journal of research and development in pharmacy and life
science june-july-2013,vol-2, p.g.no:464-474

40. THANK YOU