Ocular ointments, Ocular gels, Ocular Solutions, Ocular Suspensions, Hard and Soft contact lenses, etc.

2. • Ocular administration of drug is associated with the need
to treat opthalmic diseases.
• Eye is most easily accessible site for topical
administration of medication.
• Ideal opthalmic drug delivery system is the one which is
able to sustain the drug release and to remain in the
vicinity of front of the eye for prolonged period of time.
• Most ocular treatments call for the topical administration
of opthalmically active drugs to tissue around the ocular
activity.
• Most prescribed dosage form is the “Eye Drops”.

3. • Good corneal penetration
• Prolonged contact time with the eye
• Less drainage tendency
• Simplicity of instillation for patient
• Non-irritating and comfortable
• Appropriate rheological properties
• Sterile
• Free from foreign particles
• Isotonic with the tear fluid
• Minimum protein binding
• Good bioavailability
• Ideal pH should be 7.4

5. The cornea, lens, vitreous bodies all are transparent media with no blood vessels.
Thin epithelial layer covers the cornea which is continuous with the conjunctiva.
Bulk of cornea is formed of cris-crossing layers of the collagen & is bounded by elastic
laminae on both i.e front & back.
Eye is constantly cleaned & lubricated by the lacrimal apparatus which consists of 4
structures:
1. Lacrimal glands
2. Lacrimal canals
3. Lacrimal sac
4. Nasolacrimal duct
Lacrimal fluid secreted by the lacrimal glands is emptied on the surface of the
conjunctiva of the upper eyelid .
Lacrimal fluid in human has a normal volume of 7mcg.
It contains enzymes ‘lysozymes’ which is bactericidal.
Composition of tear:
a. Water-98.2%,
b. Solids-1.8%,
c. Organic elements- Proteins (0.67), NaCl (0.66%), Sugar (0.65%)

8. • Non- corneal absorption:
Penetration across sclera & conjunctiva into intra ocular
tissues.
Non productive: because penetrated drug is absorbed by
general circulation.
• Corneal absorption:
Outer epithelium: rate limiting barrier, with pore size 60a, only
access to small ionic and lipophilic molecules.
Trans cellular transport: transport between corneal epithelium
and stroma.

13. TYPES OF CONVENTIONAL ODDS
Eye drops
Opthalmic ointments
Opthalmic gels
Eye lotions
Inserts
CATEGORIES OF DRUGS USED IN ODDS:-
Miotics (pupil to contract)
Mydriatics (pupil ton dilate)
Diagnostics
Surgical adjuncts
Anti bacterial / Anti infectives

14. • Eye Drops:-
Drugs which are active at eye or eye surface are widely
administered in the form of Solutions, Emulsion and
Suspension.
Various properties of eye drops like hydrogen ion
concentration, osmolality, viscosity and instilled volume
can influence retention of a solution in the eye.
Less than 5 % of the dose is absorbed after topical
administration into the eye.
The dose is mostly absorbed to the systemic blood
circulation via the conjunctival and nasal blood vessels.
3 Types:-
Solutions, Suspensions, Emulsions

15. 1. Opthalmic solution:-
Sterile homogenous preparation which is free from the foreign particles,
prepared for the instillation of medication into the eye.
Ex. Timolol opthalmic solution (Timoptic, Timoptic-XE), Azithromycin eye
drops (Azasite)
2. Opthalmic Suspension:-
Sterile disperssions of finely divided insoluble API in an aqueous solvent
consisting of suitable suspending and dispersing agent
Its activity is particle size dependent. So if size is optimum then optimal
activity is achieved.
Ex. Tobramycin 0.3% + Dexa 0.05% (TobraDex ST) have very low settling
rate
3. Emulsions:-
Fine sterile dispersion of minute droplets of one liquid into another, in which
it is generally not soluble or miscible.
Ex. (w/o emulsion) Cyclosporin 0.05% opthalmic emulsion (Restasis)
(o/w emulsion) Fluribrophen axetil + Castor oil (Fluribrophen opthalmics)
have better bioavailability and less irritation.

16. • OPTHALMIC OINTMENTS :-
Mixture of semisolid and solid hydrocarbons (parrfins)
which melts at ocular
Temperature of 34 C.
When applied to inferior conjuctival sac, ointments melt
quickly and the excess spread out onto the lid margin,
lashes, skin of lids.
It has a therapeutic effect for 6hr.
Prolongation of drug contact time with the external
ocular surface can be achieved using ophthalmic
ointments, but the major drawback of this dosage form
such as blurring of vision & matting of eyelids can limit
its use.
Ex. Tobramycin opthalmic ointment (Tobrex)

17. • Opthalmic gels:-
Sterile semisolid cross linked system
which is meant for administration of drug
into the eye.
Ex. Pilocarpine gel (Pilopine HS)
• Opthalmic lotion:-
Low to heavy viscosity topical preparation
meant for cleansing of eyes.
Ex. Eye Drops Smile 40 EX Mild Eye
Lotion

19. 2 TYPES OF OPTHALMIC INSERTS :-
Non-erodible inserts- Ocuserts & Contact lens
Erodible inserts- Lacriserts, SODI, Minidisc
DESIRED CRITERIA FOR OCULAR INSERTS :-
Comfortable
Ease of handling & insertion
Non interfering with vision & oxygen permeability
Reproducibility of release kinetics
Sterility
Stability
Ease of manufacture

20. It is medicated novel
ocular drug delivery
system which can be
inserted into the eye.
Ex. Pilocarpine ocusert
(Ocusert Pilo-20, Pilo-
40)

21. Hard contact lenses, soft contact lenses
and intraocular lenses are popular for
correction of refractive errors of the eye and
several kinds of polymer have been used
for the preparation .
Therapeutic soft lenses are often used to aid
corneal wound healing in patient with infection,
corneal, ulcers, characterised by marked
thinning of the cornea.
2 types of contact lenses :-
Disposable lenses
Non-disposable lenses
E.g. Bionite ® was developed by Griffin
laboratory, and Soflens®, was developed by
Bausch & Lomb, They used fluoresce in
as a model drug.
Antiviral idoxuridine (IDU), polymyxin B and
pilocarpine as drug delivery by soft Conact
Lenses to the eye.

22. Sterile rod shaped device
made of hydroxy propyl
cellulose without any
preservative i.e used in
the treatment of dry eye
syndromes.
Advantage:-
Replacement of 4 times
an hour regimen by once
or twice daily regimen is
the benefit achieved by
this dosage form.

23. • Sterile thin films of oval
shape, which after
introduction into the inferior
cul-de-sac are wetted by the
tear & then gets soften in
10-15 mins  viscous
polymer mass (10-15 mins)
 polymer solution (30-60
mins)
• ADVANTAGE:-
SODI application has been
reported to replace 4-12 drops
instillation or 3-6 applications
of ointment for treatment of
glaucoma & trachoma

24. • Ocular therapeutic
system (OTS) consists
of a countered disc
with a convex front
and a concave back
surface in the contact
with eyeball.
• It is like a mimiature
contact lens with a
diameter of 4-5 mm.

25. The inserted ocusert in cul-de-sac, dissolved in lacrimal fluid,
penetrating into system by zero order kinetics.
It can be given by the following equation:-
(dQ/dt)r = Dp.Km.(Cr-Ct)
hm
Where,
(dQ/dt)r = Rate of release of Pilolcarpine
Dp = Diffusivity of Pilocarpine
hm = Thickness of membrane
Km = Partition corefficient
(Cr-Ct) = Difference in the Pilocarpine cone between reservoir in
the core & tear fluid

26. If Cr>>Ct then the above equation can be simplified to:-
(dQ/dt) =Dp.Km.Cs/hm
Where, Cs = Saturated Pilocarpine solution.
ADVANTAGES OF OCUSERTS:-
Accurate and programmed dosing
Provides better patient compliance
Less frequency of dosing
Fewer ocular and systemic side effects
Free from preservatives

27. 1. Inflow & Outflow of Lacrimal fluids.
2. Efficient naso-lacrimal drainage.
3. Interaction of drug with proteins of Lacrimal fluid.
4. Dilution with tears.
5. Limited and poor corneal permeability
6. Metabolism

28. RESCENT FORMULATION TRENDS IN
OCDDS FOR THE ENHANCEMENT OF
BIOAVAILABILITY :-
1. ADDITION OF VISCOSITY ENHANCER
Increases viscosity of the solution  there by decreasing solution
drainage
Slows elimination rate from the precorneal area and enhances
contact time.
Generally hydrophilic polymers- ex. Methyl cellulose, polyvinyl
alcohols, polyacrylic acids, sodium carboxy methyl cellulose,
carbomer are used.
A minimum viscosity of 20 cst is needed for optimum corneal
absorption.

29. 2. USE OF PENETRATION ENHANCER
Substances which increase the permeability characteristics of the
cornea by modifying the integrity of corneal epithelium are
known as penetration enhancers.
Modes of action:-
Penetration enhancers act mainly on tight junctions, modify the
integrity of the corneal epithelium & hence increase the
permeability of the cell membrane.

30.  Chelators :
e.g. EDTA, Salicylates
 Surfactants :
e.g. palmiloyl carnitine , sodium caprate, Sodium dodecyl sulphate
 Bile acids and salts :
e.g. Sodium deoxycholate, Sodium taurocholate, Sodium taurodeoxycholate, Taurocholic acid
 Glycosides :
e.g. Saponins, Digitonon
 Fatty acids :
e.g. Caprylic acid
 Miscellaneous :
e.g. Azone, Cytochalasins
 Preservatives :
e.g. Benzalkonium chloride
 Glycosides:-
e.g. Saponin, Digitonin

31. 3. PRODRUGS
Prodrugs enhance corneal drug permeability through
modification of the hydrophilicity or lipophilicity of the drug.
The method includes modification of chemical structure of the
drug molecule, thus making it selective, site specific and a safe
ocular drug delivery system.
Drugs with increased penetrability through prodrug formulations
are epinehrine, phenylephrine, timolol, pilocarpine

32. 4. USE OF MUCOADHESIVES IN OCULAR DRUG
DELIVERY SYSTEMS
Polymeric mucoadhesive vehicle: Retained in the eye due to non-
covalent bonding with conjunctival mucine.
Mucine is capable of picking of 40-80 times of weight of water.
Thus prolongs the residence time of drug in the conjuctival sac.
Mucoadhesives contain the dosage form which remains adhered to
cornea until the polymer is degraded or mucus replaces itself.
Types-
1. Naturally Occurring Mucoadhesives- Lectins, Fibronectins
2. Synthetic Mucoadhesives-PVA,Carbopol, carboxy methyl
cellulose, cross-linked polyacrylic acid
Drugs incarporated in to these are pilocarpine, lidocaine, benzocaine
and prednisolone acetate.

33. • The polymer undergoes
swelling in water,
• Entanglement of the
polymer chains with
mucin on the epithelial
surface.
• The un-ionized carboxylic
acid residues on the
polymer form hydrogen
bonds with the mucin.
• The water-swellable yet
water-insoluble systems
are preferred

34. 5. USE OF POLYMERS
Incorporation of polymers into an aqueous medium increases the
viscosity there by improving the ocular contact time of drug
solution .
An optimal viscosity of 12-15 cps has been suggested for ocular
drug absorption.
Hydrophilic polymers- Ethyl acetate, Poly vinyl acetate, Poly
acrylic acid
Hydrophobic polymers- Shellac, Glycerin monostearate, Nylon,
Poly vinyl chloride

36. 6. PHASE TRANSITION SYSTEM
Temperature dependent phase transition system e.g. Lutrol
FC 127 and Poloxamer 407
Triggered transition system PH e.g. Cellulose acetate
phthalate, Carbopol, Chitosan
Ion activated system gelrite - An ion activated in situ
gelling polymer forms a clear gel in the presence of cation.
e.g. Calcium or sodium ions present in the tears increase
the corneal residence time & bioavailability of drugs.

37. POLYMERS MECHANISM
Lutrol FC –
127 and
Poloxamer
407
Viscosity increased when their
temperature raised to eye
temperature.
Cellulose
acetate
phthalate latex
Coagulates when its native pH 4.5
raised by tear fluid to pH 7.4
Gelrite Forms clear gel in the presence of
cations
37

38. 7. COLLAGEN
SHIELDS:-
Collagen is the structural
protein of bones, tendons,
ligaments, & skin and
comprises more than 25% of
the total body weight.
Collagen shields belong to
soluble ophthalmic inserts
manufactured from Procine
scleral tissue.
Cross linked collagen shields
might be useful in ocular drug
delivery devices because they
can allow drug concentrations
to achieve higher levels in
cornea & aqueous humor.

39. ADVANTAGES
• Appropriate delivery system for both hydrophilic and
hydrophobic drugs with poor penetration properties
• Biological inertness, structural stability, good
biocompatibility and low cost of production.
DISADVANTAGES
• Insertion technique is difficult & expulsion of shields may
occur
• Not individually fit for each patient
• Shields are not fully transparent & thus reduce visual
activity.

40. 8. PSEUDOLATICES :-
Organic solution of polymers is dispersed in an
aqueous phase to form O/W emulsion
Water is removed partially to an extent that
residual water is removed sufficient enough to
keep polymeric phase discrete & dispersed
On application leave an intact noninvasive
continuous polymer film which reserves drugs
Drug released slowly over prolonged period of
time , better ocular bioavailability patient
compliance

41. 9. PARTICULATE SYSEM :-
(NANOPARTICLES & MICROSPHERES)
Nanoparticle- <1 micrometre
Microparticle- >1 micrometre
The maximum size limit for microparticles for ophthalmic
administration is about 5-10 micrometer above which a
scratching feeling in the eye can result upon ocular instillation.
That is why micro and nanoparticles are promising drug
carriers for ophthalmic application.

42. The drugs are bound to
small particles which
are then dispensed in
aqueous vehicles
Polybutylcyanoacrylate
nanoparticles have
been used for human
being as a drug carrier

43. 10. VESICULAR SYSTEM TYPES
1.- LIPOSOMES
2.- NIOSOMES
3.- DISCOSOMES
4.- PHARMACOSOMES

44. LIPOSOMES:-
Liposomes are biocompatible
& biodegradable lipid vesicles
made up of natural lipids and
about 25–10 000 nm in
diameter.
They are having an intimate contact with the corneal and conjunctival
surfaces which is desirable for drugs that are poorly absorbed, the drugs
with low partition coefficient,
poor solubility or those with medium to high molecular weights and
thus increases the probability of ocular drug absorption.
Advantage:-
Acurate dosing & improved bioavailability for lipophillic drugs.

45. NIOSOMES :-
The major limitations of liposomes are chemical instability, oxidative degradation
of phospholipids, cost and purity of natural phospholipids.
To avoid this niosomes are developed as they are chemically stable as compared to
liposomes and can entrap both hydrophobic and hydrophilic drugs.
They are non toxic and do not require special handling techniques.
Niosomes are nonionic surfactant vesicles that have potential applications in the
delivery of hydrophobic or amphiphilic drugs.

46. Non ionic surface active agent
Phospholipid
Hydrophilic drugs in aqueous
region encapsulated
Lipophilic drugs located in the
hydrophobic lamella
Niosomes are microscopic lamellar structures, which are formed on the
admixture of non-ionic surfactant of the alkyl or dialkyl polyglycerol ether
class and cholesterol with subsequent hydration in aqueous media.
Structurally, niosomes are similar to liposomes, in that they are also made up
of a bilayer. However, the bilayer in the case of niosomes is made up of non-
ionic surface active agents rather than phospholipids as seen in the case of
liposomes.

47. DISCOMES:-
Soluble surface active agents when added in critical amount to
vesicular dispersion leads to solubilization or breakdown of
vesicles & translates them into mixed micellar systems
E.g: Egg yolk phosphatidyl choline liposomes by the addition of
non ionic surfactants of poly oxy ethylene cetyl ether till the
lamellar and mixed lamellar coexist
Advantages:
Minimal opacity imposes no hinderance to vision
Increased patient compliance
Zero order release can be easily attained

48. PHARMACOSOMES:-
This term is used for pure drug vesicles formed by the amphiphilic
drugs.
The amphiphilic prodrug is converted to pharmacosomes on dilution
with water.
The vesicle formation takesplace not only just by association of
phospholipids but also by amphiphilic molecular association
Since many drugs are also amphiphiles, they can form the vesicles
Advantages:
Drug metabolism can be decreased
Controled release profile can be achieved

49. The new ophthalmic delivery
system (NODS) is a method of
method of presenting drugs to
the eye within a water soluble
drug loaded film.
It provide for accurate,
reproducible, dosing in an
easily administered
preservative free form.
Each NODS consists of a drug
loaded film or (flag) attached to
a handle film by means of thin
membrane.
Shape and Area – 22 mm2
Thickness – 20 µm
Total weight - 500 µg (of which
40% can be drug. )

50. 1. Implants:
For chronic ocular diseases like cytomegalovirus (CMV) retinitis, implants
are effective drug delivery system. Earlier non biodegradable polymers
were used but they needed surgical procedures for insertion and
removal.
Presently biodegradable polymers such as Poly Lactic Acid (PLA) are
safe and effective to deliver drugs in the vitreous cavity and show no
toxic signs.
Ex. Retisert® (non-biodegradable fluocinolone acetonide intravitreal
implant; Bausch & Lomb) sterile implant consists of a tablet containing
0.59 mg fluocinolone acetonide.
Ozurdex® (biodegradable dexamethasone intravitreal implant;
Allergan, Irvine, CA.) is composed of a biodegradable copolymer of lactic
acid and glycolic acid with micronized dexamethasone. This implant is
placed into the vitreous cavity using a single-use applicator.
2. Dendrimer:
Dendrimers can successfully used for different routes of drug
administration and have better water-solubility, bioavailability and
biocompatibility.

51. 2. Iontophoresis:
In Iontophoresis direct current drives ions
into cells or tissues. For iontophoresis the
ions of importance should be charged
molecules of the drug.
Positively charged of drug are driven into
the tissues at the anode and vice versa.
Ocular iontophoresis delivery is not only
fast, painless and safe but it can also
deliver high concentration of the drug to a
specific site.

52. • 4. Microemulsion:
Microemulsion is dispersion of water and oil stabilized using surfactant and co-
surfactant to reduce interfacial tension and usually characterized by small
droplet size (100 nm), higher thermodynamic stability and clear appearance.
Selection of aqueous phase, organic phase and surfactant/co-surfactant
systems are critical parameters which can affect stability of the system.
• 5. Nanosuspensions:
Nanosuspensions have emerged as a promising strategy for the efficient
delivery of hydrophobic drugs because they enhanced not only the rate and
extent of ophthalmic drug absorption but also the intensity of drug action with
significant extended duration of drug effect.
For commercial preparation of nanosuspensions, techniques like media milling
and high-pressure homogenization have been used.

53. • 6. Microneedle:
Microneedle had shown prominent in vitro penetration into sclera and rapid
dissolution of coating solution after insertion while in vivo drug level was
found to be significantly higher than the level observed following topical
drug administration like pilocarpine.
• 7. Mucoadhesive Polymers:
They are basically macromolecular hydrocolloids with plentiful hydrophilic
functional groups, such as hydroxyl, carboxyl, amide and sulphate having
capability for establishing electrostatic interactions.
A mucoadhesive drug formulation for the treatment of glaucoma was
developed using a highly potent beta blocker drug, levobetaxolol (LB)
hydrochloride and partially neutralized poly acrylic acid .

54. % MOISTURE ABSORPTION :
It was carried out to check the physical stability or integrity
at wet condition.
The prepared ocusert was accurately weighed and placed in a
dessicator containing aluminium chloride with 79.5% moisture
and it was kept for 3 days.
The ocusert was taken out and reweighed after 3 days.
% Moisture absorption = Final weight – Initial weight x 100
Initial weight

55. • % MOISTURE LOSS:
The prepared ocusert was initially weighed and kept in a
dessicator containing fused anhydrous calcium chloride and it
was kept for 3 days.
The ocusert was taken out and reweighed after 3 days.
% Moisture loss = Final weight – Initial weight x 100
Initial weight

56. • UNIFORMITY OF THICKNESS:
The thickness of the insert was determined using a Vernier
caliper at five separate points of each insert.
For each formulation, five randomly selected inserts were
tested for their thickness.
• UNIFORMITY OF WEIGHT:
From each batch, five inserts are taken out and weighed
individually using digital balance (Asco, India). The mean
weight of the insert is noted.

57. • IN-VITRO EVALUATION METHODS
• BOTTLE METHOD:
In this, dosage forms are placed in the bottle containing
dissolution medium maintained at specified temperature and
pH.
The bottle is then shaken.
A sample of medium is taken out at appropriate intervals and
analyzed for the drug content.
• DIFFUSION METHOD:
Drug solution is placed in the donor compartment and buffer
medium is placed in between donor and receptor compartment.
Drug diffused in receptor compartment is measured at various
time intervals.

58. • MODIFIED ROTATING BASKET METHOD:
Dosage form is placed in a basket assembly connected to a stirrer.
The assembly is lowered into a jacketed beaker containing buffer
medium and temperature 37 degrees Centigrade.
Samples are taken at appropriate time intervals and analyzed for
drug content.
• MODIFIED ROTATING PADDLE APPARATUS:
Here, dosage form is placed into a diffusion cell which is placed in
the flask of rotating paddle apparatus.
The buffer medium is placed in the flask and paddle is rotated at 50
rpm.
The entire unit is maintained at 37 degree C.
Aliquots of sample are removed at appropriate time intervals and
analyzed for drug content.

59. Then the dosage form is removed carefully at regular time
interval and are analyzed for drug content.
The drug remaining is subtracted from the initial drug content,
which will give the amount of the drug absorbed in the eye of
animal at particular time.
After one week of washed period, the experiment was
repeated for two time as before.
Here, the dosage form is applied to one eye of animals and the
other eye serves as control.

60. These are carried out to predict the breakdown that may
occur over prolonged periods of storage at normal shelf
condition.
Here, the dosage form is kept at elevated temperature or
humidity or intensity of light, or oxygen.
Then after regular intervals of time sample is taken and
analyzed for drug content.
From these results, graphical data treatment is plotted and
shelf life and expiry date are determined.

61. DRUG BRAND NAME FORM USE
Ozurdex Dexamethasone Intravitreal
implant
To treat swelling due to
blockage of certain blood
vessels
Lotemax Ioteprednol Eye drops To treat post operative
inflammation
Omnipred ,
Pred Forte
Prednisolone
acetate
Eye drops To treat inflammation of eyes,
eyelids.
Treatment of keratitis
Retisert Fluconazole Ophthalmic
implant
Treat inflammation within eye
due to infection & diseases
Atropine care Atropine Ophthalmic
solution
Mydriaticts, Treatment of
certain inflammation
conditions within the eye
Alrex Ioteprednol Eye drops Relief of temporary itching,
redness, swelling & irritation
of eye caused by seasonal
allergies
Volaren Diclofenac Eye drops
(NSAID)
Treating pain, redness,
swelling & sensitivity to light
after certain eye surgeries

62. Biopharmaceutics & Pharmacokinetics; Brahmankar &
Jaiswal, 1st Edition, 368-369.
Novel drug delivery systems: Y. W. Chein, 2nd Edition, 269-
300.
Controlled and Novel drug delivery; N. K. Jain, 1st Edition,
82-92.
Advances in controlled and novel drug delivery system,
N.K. Jain, 1st Edition, 218-223.
Encyclopedia of controlled drug delivery system, Edith
Mathionwitz, Vol.2, 1563-1576.
Modern Pharmaceutics; Banker & Rhods, 3rd Edition, 489-
541.