The document is a comprehensive guide on ocular drug delivery systems, covering various formulations such as solutions, suspensions, ointments, and novel delivery mechanisms like ocular implants and iontophoresis. It discusses anatomical and physiological barriers to drug absorption in the eye, as well as recent advancements aimed at improving bioavailability and therapeutic efficacy. The guide concludes with insights into the future of drug delivery systems in ophthalmology, emphasizing the need for ongoing research and development.

1. OCULAR DRUG DELIVERY
SYSTEM
GUIDE BY PROF.
G.S.LAD
JOGDAND MAHESH PARMESHWAR -15
1

2. CONTENTS
2
 INTRODUCTION
 RELEVANT ANATOMY AND PHYSIOLOGY OF THE EYE
 PATHWAYS OS DRUG ABSORBTION
 FORMULATION SYSTEMS
 RESCENT DEVELOPMENT IN OCULAR INSERT DRUG
DELIVERY SYSTEM
 ADVANTAGES
 CONCLUSION
 REFERENCES

3. INTRODUCTION
3
 Ophthalmic preparations are the sterile product, meant for the instillation in to the eye in the
space between the eyelid and the eyeball. These products must be isotonic with lachrymal
secretion to avoid discomforts and irritations. The pH should be controlled up to 7.4 to avoid
irritations. Vehicles in the preparation must have good wetting ability to penetrate cornea and other
tissues. Ophthalmic products include: -
 Solution
 These are the sterile aqueous solutions used for washing of eyes. The eye solutions are supplied
in concentrated form and are required to be diluted with warm water immediately before use. They
are usually applied with a clean eye- bath or sterilized fabric dressing and a large volume of
solution is allowed to flow quickly over the eye
 E.g.: - Sodium chloride eye lotion B.P.C - Sodium bicarbonate eye lotion
 Suspension
 Eye suspensions are not commonly used, as compared to eye drops. They are prepared only in
those cases, when the drug is insoluble in the desired vehicle or unstable in liquid form they are
also used to produce the sustained action of the preparation. The particle size of the suspension
should be fine to avoid irritation. The preparation shaken thoroughly before use in order to
distribute the drug particles uniformlyE.g.: - Pilocarpien suspension - Nitroglycerin suspension
 Ointment
 Eye ointments are sterile preparations meant for application to the eye. These are prepared under
aseptic conditions and packed in sterile collapsible tubes, which keep the preparation sterile until
whole of it is consumed. The ointments have longer contact time with eye and produce sustained
action. It has greater storage stability. The application of ointment producing film over the eye and
blurring vision may occur.
 E.g.: - Atropine eye ointment B.P - Chloramphenicol eye ointment

4. 4
RELEVANT ANATOMY AND PHYSIOLOGY OF THE EYE

5. PATHWAYS OF DRUG ABSORPTION
5
 DISTRIBUTION AND DISPOSITION OF DRUGS
Physiological barriers to diffusion and productive absorption of
topically applied drug exit in precorneal and corneal space.
The precorneal constraints responsible for poor ocular
bioavailability of conventional ophthalmic dosage forms are
solution drainage, lacrimation, tear dilution, tear turnover and
conjunctival absorption.
 Drug solution drainage away from the precorneal area has
been shown to be most significant factor in reducing the
contact time of the drug with the cornea and consequently
ocular bioavailability of topical dosage forms. The instilled
dose leaves the precorneal area within 2 minutes of instillation
in humans. The drainage allows the drug to be absorbed
across the nasal mucosa into the systemic circulation. The
conjunctiva also possesses a relatively large surface area,
5times the surface of cornea making the loss significant. Both
the conjuctival and nasal mucosa have been indicated as the main
potential sites for systemic absorption of topically applied drugs.


6. 6

7. 7
 REQUIREMENTS OF CONTROLLED OCULAR DELIVERY
SYSTEM
 To overcome the side effect of pulsed dosing produced by
conventional system
 To provide sustained and controlled drug delivery
 To increase the ocular bioavailablity of drug by increasing
corneal contact time
 To provide targeting with in the ocular globe so as to prevent the
loss of other ocular diseases
 To provide comfort and complaints to the patient and yet improve
therapeutic performance of the drug over conventional systems
 To provide the better housing of the delivery system in the eye so
as the loss to other tissues besides cornea is prevented

8. FORMULATION SYSTEMS
8
 1-Polymeric Solution: -
 The addition of polymers like methylcellulose, polyvinyl alcohol, hydroxypropyle cellulose
and polyvinyl pyrrolidone to the eye drop solution increases the corneal penetrations of
drug. This is presumably due to on increases tear viscosity, which decreases the other
wise rapid initial drainage rate, increases the corneal contact time and thus sustains to
some extant the initial tear concentration of the drug.
 2-Phase Transition Systems: -
 These are liquid dosage forms which shift to the gel or solid phase when instilled in the
cul-de-sac. Polymers that are normally used are Lutrol FC-127and poloxamer 407 whose
viscosity increases when its temperature raised to 37° C. cellulose acetate phthalate too
coagulates when its native pH of 4.5 is raised by tear fluid to pH 7.4.
 3-Mucoadhesive/Bioadhesiv: -
 Any polymer solution/suspension placed in the eye first encounters mucin at the cornea
and conjunctival surface. Bioadhesive/Mucoadhesive systems can be either polymeric
solution or microparticle suspensions.They are retained in the cul-de-sac through adhesive
bonds established with the mucins or the epithelium thus increasing the corneal contact
time. However water-soluble polymers face the disadvantage of having a short half-life.
Muchoadhesive polymers are usually macromolecular hydrocolloids with numerous
hydrophilic functional groups. These groups are, carboxyl, hydroxyl, amide and sulphate.
They establish electrostatic and hydrophobic interactions and hydrogen bonding with the
underlying surface. A good bioadhesive should exhibit a near zero contact angle to allow
maximalcontact with the mucin coat. The structural factors like chain flexibility and
molecular weight also influence the bioadhesion. To diffuse and penetrate into mucin layer,
flexibility in chain of polymer is required. The entanglement with mucin coat increases the
adhesive strength of polymer. Generally, an increase in molecular weight to a critical
value, increases the bioadhesiveness. pH and ionic strength of dosage forms also affect

9. FORMULATION SYSTEMS
9
 4-Collagen Shields: -.Collagen corneal bandages in the shape of a contact lens an alternative to
soft contact lenses. For drug delivery, the shields are rehydrated in a water solution of the drug,
whereby the drug is absorbed by the protein matrix and is released once the shield dissolves in
the eye. Water-soluble drug is incorporated at the time of manufacture. The simplicity of use and
the convenience afforded by shields make them an attractive delivery device.Crosslinking of
collagen corneal shield affects ofloxacin bjoavailability. As the dissolution times for the cross
linked collagen shield are longer than those of the non-cross-linked type, they serve as drug
reservoirs. Therefore, cross-linked collagen shields might be useful ocular drug delivery devices
because they can allow drug concentrations to achieve higher levels in the cornea and aqueous
humor. Some drawbacks of these devices are: application of shield requires to anaesthetize the
cornea and they often produce some discomfort and interfere with vision.
 5-Pseudolatices: -Organic solution of polymer is dispersed in an aqueous phase to form a o/w
type emulsion subsequently using appropiate means, i.e. by applying vacuum, or by using
controlled temperature. Water is removed partially to an extent that residual water is sufficient
enough to keep polymeric phase discrete and dispersed. Such dispersions are referred to a
pseudolatices which on application leave an intact non invasive continuous polymer film which
reserves drug. The drug from such systems is released slowly over a prolonged period if time
ensuring better ocular availability and patient compliance by avoiding frequent instillation of
preparation.
 6-Ocular Penetration Enhancers: -Penetration enhancers like actin filament inhibitors,
surfactants, bile salts, chelators and organic compounds have been used to increase the
bioavailability of topically applied peptides and proteins which ate otherwise poorly absorbed due
to unfavorable molecular size, charge, hydrophilic as well as their susceptibility to degradation by
peptidases in the eye.
 7-Ocular Iontophoresis: -Iontophoresis is the process in which the direct current derives ions
into cell or tissues. Antibiotics, antifungals, Anesthetic agents and adrenergic agents have been
tried by this method

10. 10
 Ocusert by Alza.
 Pilocarpine, a parasympathomimetic agent for glaucoma .Act on target organs in the iris, ciliary body and
trabecular meshwork Copolym
Ethylene-vinylacetate
 Carrier for pilocarpine : alginic acid in the core of Ocusert
 White annular border : EVA membrane with titanium dioxide (pigment) (easy for patient to visualize)
 Lacrisert by Merck:
 Patients with dry eyes (keratitis sicca) A substitute for artificial tears Placed in the conjunctival sac and softens
within 1 h and completely dissolves within 14 to 18 hr .Stabilize and thicken the precorneal tear film and prolong
the tear film break-up time
 Ophthalmic gel for pilocarpine:
 Poloxamer 407 (low viscosity, optical clearity, mucomimetic property)
 Ophthalmic prodrug:
 Dipivalylepinephrine (Dipivefrin)
 Lipophilic :- increase in corneal absorption
 Esterase within cornea and aqueous humor
 Fig 5. Ocusert ocular therapeutic systems are thin, flexible wafers placed under the eyelid to provide a week's
dosage of pilocarpine in the treatment of glaucoma. Ocuset system cause less blurring of vision than pilocarpine
eye drops, which must be used 4 times daily
EXAMPLES OF OCULAR DRUG DELIVERY SYSTEMS

11. Recent developments in ocular insert drug-
delivery systems:
11
 Ocular implants
 Treating the posterior segment
 Historically, the posterior segment has been exceptionally difficult to treat owing to
the many barriers that obstruct ingress of foreign matter into the eye. The
development of ocular implants has allowed these external barriers to be overcome.
Modern devices allow long-term treatments for otherwise impossible to treat
conditions, and many devices provide medication for years from a single procedure
 Drug delivery by intravitreal injection
 There are many debilitating and sight threatening conditions resulting from
posterior segment diseases and in most cases the only way these can be treated is
by invasive procedures, for example, ‘intravitreal injection’. In the main this still
remains so, however, developments have brought a diverse range of effective
implantable drug-delivery systems targeting posterior segment disease and the
various options will now be considered
 Intraocular implants
 In an attempt to overcome the problem of frequent injections biodegradable and
nonbiodegradable drug depot devices that can offer long-term drug release into the posterior
chamber have been developed and further research in this area is ongoing. Solutions,
liposomes, micelles, nanoparticles and vectosomes are suitable for intravitreal injection,
although these dosage forms only give short-term drug availability, generally days to several
weeks

12. ADVANTAGES AND DISADVANTAGES
12
Table 1. Advantages and disadvantages using ocular inserts.
Advantages Disadvantages
•• Increased residence
time/bioavailability
•• Precision dosing with controlled
release, avoids pulsate drug
delivery
•• Minimal systemic absorption
•• Administration frequency
reduced
•• Conjunctival/scleral route to
internal target
•• Better shelf life and no
preservatives
•• Combinational therapeutic
approaches
•• Physical and psychological
obstacles of placing solid objects
on the eye, foreign body sensation.
•• Movement around the eye could
interfere with vision.
•• Potential accidental loss
•• Some devices difficult to insert
or remove
•• Potential burst release upon
insertion prior to controlled delivery

13. Conclusion And Future outlook
13
 Ocular indication of controlled-release systems
 Short, topical ocular half-life
 e.g., heparin for ligneous disease
 Small, topical ocular, therapeutic index
 e.g., pilocarpine for chronic open-angle glaucoma , possibly nucleside, antiviral
 Systemic side effects
 e.g., timolol for glaucoma and cyclosporin A for graft rejection
 Need for combination therapy
 e.g., cromoglycate and corticosteroid for asthma and allergies
 The need for a predetermined profile of drug delivery over a prolonged period of days, weeks, or
months
 e.g., acute corneal infections, acute-becoming chronic inflammation, and corneal graft rejection
episodes
 Long-continued low dosage for therapy or prophylaxis
 e.g., for prevention of corneal graft rejection, prevention of recrudescence of inflammation, and
prevention of, or recurrence of, herpetic disease.
The technologies described here represent small fraction of the development of drug delivery
systems and few of them are still at experiment level. The need for research into drug delivery
systems extends beyond ways to administer new pharmaceutical therapies. The safety and efficacy
of current systems can be improved if their delivery rate, biodegradation, and site-specific targeting
can be predicted, monitored, and controlled. Which the help of rapid advances in biotechnology,
chemistry, and chemical engineering, it will be possible for researchers to obtain drug delivery
systems with minimum side effects and maximum effectiveness

14. Reference
14
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