1 Pharmaceutics III

Chapter 4

Ophthalmic Preparations
by
Ass. Prof. Abdulla El Madani

Faculty of Pharmacy
Al zaytoonah University

2023/2024
2 Ophthalmic drug delivery

• Topical drug administration to the eye aims to treat conditions such as:
– Bacterial/fungal/viral infections
– Allergic/infectious conjunctivitis
– Elevated intraocular pressure and glaucoma
– Dry eye

• Ophthalmic preparations require special consideration with regard to

sterility, preservation, isotonicity, buffering, viscosity, ocular
bioavailability, and packaging
3 Sterility and preservation

• Autoclaving not always feasible (thermal instability).

• Sterile filtration is used instead.
• Single-use formulations are preservative-free.
• Multi-use formulations should contain antimicrobial preservatives to maintain
sterility during use.
– e.g. benzalkonium chloride, thimerosal, phenylmercuric acetate (none of
these alone is effective against Pseudomonas aeruginosa)
– For P. aeruginosa, a combination of benzalkonium chloride and
polymyxin B or disodium edetate is used
 4 Ophthalmic preparations
 Definition: They are specialized dosage forms designed to be instilled onto the
external surface of the eye (topical), administered inside (intraocular) or
adjacent (periocular) to the eye or used in conjunction with an ophthalmic
device.

 The most commonly employed ophthalmic dosage forms are solutions,

suspensions, and ointments.
 these preparations when instilled into the eye are rapidly drained away from the
ocular cavity due to tear flow and lacrimal nasal drainage.

 The newest dosage forms for ophthalmic drug delivery are: gels, gel-forming
solutions, ocular inserts , intravitreal injections and implants.
5

Anatomy and Physiology of the Eye

6 Anatomy and Physiology of the Eye
7
8
 The sclera: The protective outer layer of the eye, referred to as the “white of the
eye” and it maintains the shape of the eye.

 The cornea: The front portion of the sclera, is transparent and allows light to enter
the eye. The cornea is a powerful refracting surface, providing much of the eye's
focusing power.

 The choroid is the second layer of the eye and lies between the sclera and the
retina. It contains the blood vessels that provide nourishment to the outer layers of
the retina.

 The iris is the part of the eye that gives it color. It consists of muscular tissue that
responds to surrounding light, making the pupil, or circular opening in the center of
the iris, larger or smaller depending on the brightness of the light.
 The lens is a transparent, biconvex structure, encased in a thin transparent covering.
The function of the lens is to refract and focus incoming light onto the retina.

 The retina is the innermost layer in the eye. It converts images into electrical
impulses that are sent along the optic nerve to the brain where the images are
interpreted.

 The macula is located in the back of the eye, in the center of the retina. This area
produces the sharpest vision.
10

 The inside of the eyeball is divided by the lens into two fluid-filled sections.

 The larger section at the back of the eye is filled with a colorless gelatinous mass
called the vitreous humor.

The smaller section in the front contains a clear, water-like material called aqueous
humor.

 The conjunctiva is a mucous membrane that begins at the edge of the cornea and
lines the inside surface of the eyelids and sclera, which serves to lubricate the eye.
11

Conjunctival sac is the space bound by the conjunctival membrane, which is

located between the palpebral and bulbar conjunctiva. It is the space in to
which the lacrimal fluid is secreted and it opens interiorly between the
eyelids.

Why should eye drops be instilled into the lower conjunctival sac? to prevent
injury to the cornea.
 12 Absorption of drugs in the eye

Factors affecting drug availability:

1- Rapid solution drainage by gravity, induced lachrymation, blinking reflex, and
normal tear turnover:

- The normal volume of tears = 7 µl, the blinking eye can accommodate a
volume of up to 30 µl without spillage, the drop volume = 50 ul
13 lacrimal nasal drainage
14
15

2- Superficial absorption of drug into the conjunctiva and sclera and rapid removal
by the peripheral blood flow

3- Low corneal permeability (act as lipid barrier)

16 Important factors to be considered in preparing an ophthalmic
medication include the following

a. Sterility.
b. Tonicity.
c. pH, buffering.
d. Inherent toxicity of the drug.
e. Need for a preservative.
f. Solubility.
g. Stability in an appropriate vehicle.
h. Viscosity.
i. Packaging and storage of the finished product.
17 Why needs sterility of all ophthalmic preparations when the
applications used are topical?
Ophthalmic preparations must be sterile when prepared.
Pseudomonas aeruginosa is very common gram -ve bacteria which is generally
found to be present in ophthalmic products.

It may cause serious infections of cornea. It can cause complete loss of eye sight
in 24-48 hrs.
To maintain sterility in multi dose container, containing ophthalmic products, a
suitable preservative is added. The preservative should be non-toxic, non-irritant
and should be compatible with medicaments.

The ophthalmic products are generally sterilized by autoclaving, filtration through

bacteria proof filters and addition of bactericides at low temperature.
18

General safety considerations

19 General safety considerations

A. Sterility
- Ideally, all ophthalmic products should be terminally sterilized in the
final packaging.

- Only a few ophthalmic drugs formulated in simple aqueous vehicles are

stable to normal autoclaving temperatures and times (121°C for 20-30
min).
*Such heat-resistant drugs may be packaged in glass or other heat-
deformation-resistant packaging and thus can be sterilized in this
manner.

-Most ophthalmic products, however cannot be heat sterilized due to the active
principle or polymers used to increase viscosity are not stable to heat.

Most ophthalmic products are aseptically manufactured and filled into

previously sterilized containers in aseptic environments using aseptic
filling-and-capping techniques.
20

B. Ocular toxicity and irritation

- Albino rabbits are used to test the ocular toxicity and irritation of
ophthalmic formulations.
- The procedure based on the examination of the conjunctiva, the cornea
or the iris.
- E.g. USP procedure for plastic containers:
1- Containers are cleaned and sterilized as in the final packaged product.
2- Extracted by submersion in saline and cottonseed oil.
3- Topical ocular instillation of the extracts and blanks in rabbits is
maintained and ocular changes examined.
21

C. Preservation and preservatives

 Preservatives are included in multiple-dose eye solutions for

maintaining the product sterility during use.
 Preservatives not included in unit-dose package.
 The use of preservatives is prohibited in ophthalmic products that are
used at the of eye surgery
So these products should be packaged in sterile, unit-of-use containers.
 The most common organism is Pseudomonas aeruginosa that grow in
the cornea and cause loss of vision.
22

Examples of the preservatives:

1- Cationic wetting agents:
• Benzalkonium chloride (0.01%)
• It is generally used in combination with 0.01-0.1% disodium edetate
(EDTA). The chelating, EDTA has the ability to render the resistant strains
of PS aeruginosa more sensitive to benzalkonium chloride.
2- Organic mercurials:
• Phenylmercuric nitrate 0.002-0.004%
phenylmercuric acetate 0.005-0.02%.
3-Esters of p-hydroxybenzoic acid:
• Mixture of 0.1% of both methyl and propyl hydroxybenzoate (2:1)

4- Alcohol Substitutes:
• Chlorobutanol(0.5%). Effective only at pH 5-6.
• Phenylethanol (0.5%)
23

Ideal ophthalmic delivery system

24 Ideal ophthalmic delivery system

Following characteristics are required to optimize ocular drug

delivery system:
 Good corneal penetration.
 Prolong contact time with corneal tissue.
 Simplicity of instillation for the patient.
 Non irritative and comfortable form
 Appropriate rheological properties
25
26

Classification of ocular drug delivery systems

27 Classification of ocular drug delivery systems

Liquid dosage forms:

Solutions,
Suspensions,
Powders reconstitution ,
Sol to gel systems

Semisolid:
Ointments, gels.

Solid :
Ocular inserts.

Intraocular dosage forms:

Injections,
Irrigating solutions,
Implants
28

Topical Eye drops

29
Drug delivery to ocular mucosa for local treatment is associated with great
possibilities, but often also with many challenges. The physiological constraints
imposed by the protective mechanisms of the eye also result in low absorption of
drugs.
In addition, the most common means to deliver drugs to the eye is via instillation of
an aqueous solution of the drug. However, the bioavailability of a drug introduced in
this way is often very low, typically <5%, depending on its physicochemical
properties. Such low bioavailability is attributed to extensive pre-corneal drug loss
by nasolacrimal drainage. The rapid elimination of the instilled drug often results in
a short duration of therapeutic effect and, consequently, the need for a frequent
dosing regimen.
Moreover, 50–100% of instilled dose may be absorbed systemically through
drainage via the nasolacrimal duct. This could cause possible increased risk for
undesirable side effects.

For example, topical administration of beta-blockers for treatment of wide-angle

glaucoma causes systemic side effects on the heart. Accordingly, systemic
absorption of E2 solution drained through the nasolacrimal duct may increase the
risk for undesirable side effects (e.g., increased risk of breast cancer, endometrial
434 PHT Ophthalmic preparations 5/15/2024
cancer, gynecomastia, etc.).
30
A. Topical Eye drops:

Nearly all the major ophthalmic therapeutic agents are water-soluble salts.

The selection of the appropriate salt form depends on:

- Solubility
- Ocular toxicity
- The effect of pH, tonicity, and buffer capacity
- Compatibility with the total formulation
- The intensity of any possible burning sensations

The most common salt forms used are:

- Hydrochloride, sulfate, nitrate, and phosphate.
- Salicylate, hydrobromide, and bitartrate salts may used.
- For drugs that are acidic such as the sulfonamides, sodium salts is used
31 1-Solutions
- Ophthalmic solutions are sterile solutions, essentially free from
foreign particles, suitably compounded and packaged for instillation
into the eye.

Disadvantages of eye solutions:

1-The very short time the solution stays at the eye surface.
The retention of a solution in the eye is influenced by viscosity,
hydrogen ion concentration and the instilled volume.
2- Its poor bioavailability (a major portion i.e. 75% is lost via
nasolacrimal drainage)
3- The instability of the dissolved drug
4- The necessity of using preservatives.
 32
Preservatives are added to multi-dose medication bottles to inhibit microbial contamination. An
assortment of different preservative formulations has been used in ophthalmic medicines and many of
these preservatives have been linked to unwanted ocular surface side effects. Benzalkonium chloride
in particular has been linked to a number of different adverse effects, such as disruption of the tear
film as well as damage to ocular surface epithelial cells.

434 PHT Ophthalmic preparations 5/15/2024

33

434 PHT Ophthalmic preparations 5/15/2024

 34 2- suspensions
- If the drug is not sufficiently soluble, it can be formulated as a suspension.
- A suspension may also be desired to improve stability, bioavailability, or efficacy.

- The major topical ophthalmic suspension are the steroid anti-inflammatory agents
prednisolone acetate, dexamethasone, fluorometholone and rimexolone.

- Water-soluble salts of prednisolone phosphate and dexamethasone phosphate are

available; however, they have a lower steroid potency and are poorly absorbed.

- An ophthalmic suspension should use the drug in a micro fine form: usually 95% or
more of the particles have a
35
Eye drops of poorly soluble drugs are frequently formulated as suspensions.
Bioavailability of suspended drug depends on the retention and dissolution of drug
particles in the tear fluid, but these factors are still poorly understood.

434 PHT Ophthalmic preparations 5/15/2024

36 3- Powders for Reconstitution

drugs that have only limited stability in liquid form are prepared as sterile powder
for reconstitution by the pharmacist prior to dispensing to the patient.
These drugs include α-chymotrypsin, and acetylcholine.

The sterile powder is usually manufactured by lyophilization (Freeze Drying) in

individual glass vails.

Mannitol is usually used as a bulking agent and lyophilization (Freeze Drying) aid
and is dissolved in the solution with the drug prior to drying.

It was found that potassium acetate used in place of mannitol as a drying aid
product a more stable product and allows freeze- drying to lower residual moisture
content.
37 4- Gel-Forming Solutions

Solution that are liquid in the container and thus can be instilled as eye drops
but gel contact with the tear fluid and provide increased contact time with
the possibility of improved drug absorption and increased duration of
therapeutic effect.

Liquid-gel phase transition- dependent delivery systems vary according to

the particular polymers employed and their mechanisms for triggering the
transition to a gel phase in the eye take advantage of changes in temperature,
pH, ion sensitivity or lysozymes upon contact tear fluid.
38

Delivery systems based on in situ gel-formation offer an attractive alternative to

instillation of solutions because the in-situ gel increases pre-corneal drug residence
time.
The gelling process involves a phase transition in which the instilled solution forms
a gel in the cul-de-sac of the eye as a result of response to some stimuli by the
polymer. Therefore, these systems offer the dual advantage of an easy to administer
liquid formulation along with the increased residence time of a gel.
Parameters that can change and trigger this sol-gel phase transition include pH,
temperature or ionic strength of the tear fluid.
Among all in situ gel-forming systems, activation by change in ionic strength is
most effective. The advantage is based on the fact that fluctuations in pH and
temperature, which could cause changes in the gelation process, are not associated
with the ion-activated system. These fluctuations in pH could cause ocular irritation,
and storage conditions could lead to changes in temperature.

434 PHT Ophthalmic preparations 5/15/2024

39

Example of gel-forming ophthalmic solutions in the markets is:

Timolol maleate, which is used to reduce elevated intraocular pressure
(IOP) in the management of Glaucoma with the gel-forming solutions,
IOP-lowering efficacy was extended from 12 to 24 hours and thus
required only once-a-day dosing

Why should you not use Timolol eye drops with contact lenses ...

Contact lenses can absorb the medication and decrease the amount of Timolol
entering the cornea. This will affect the intraocular pressure by potentially increasing
it, thereby putting the eye at a higher risk for glaucoma progression.
 40

Inactive Ingredients in Topical Drops

The inactive ingredients in ophthalmic solution and suspension

dosage forms are necessary to perform one r more of the following
functions:
Adjust concentration and tonicity,
Buffer and adjust pH,
Stabilize the active ingredients against decomposition,
Increase solubility,
Impart viscosity,
and act as solvent or increase solubility.
The use of ingredients to impart a color, odor, or flavor is prohibited.
41 1- Tonicity and Tonicity-Adjusting Agents

The pharmacist should adjust the tonicity of an ophthalmic solution correctly

(i.e., exert an osmotic pressure equal to that of tear fluids, generally agreed to
be -qua! to O. 9% Mac).

*A range of 0.5-2.0% Na CI equivalency does not cause a marked pain

response and a range of about 0.7-1.5% should be acceptable to most persons.

* The eye seems to tolerate hypertonic solutions better than hypotonic ones.

Common tonicity adjusting ingredients include:

NaCI, KCI, buffer salts, dextrose, glycerin, propylene glycol, and mannitol.
42

The hydrogen ion concentration of the solution in which an ophthalmic drug is dissolved
may alter the therapeutic results of the drug itself. A variation of the pH often determines
the speed and the quantity of absorption of the drug and the amount of irritation which the
patient experiences on instillation.

However, not only the pH but the osmotic pressure of the resultant solution is important.
The lacrimal fluid is alkaline, with a pH of 7.4, and is isotonic with a 1.4 per cent solution of
sodium chloride. This means that the two fluids have the same osmotic pressure and in this
instance the same freezing point, at 0.9 C.

A hypotonic solution will cause passage of fluid into the ocular tissues, bringing about
congestion in an attempt to reach an osmotic balance.

A hypertonic solution, on the other hand, will cause the removal from the tissues
43
2- pH Adjustment and Buffers

 pH adjustment is very important as pH can:

1- render the formulation more stable
2- improve the comfort, safety and activity of the product.
3- enhance aqueous solubility of the drug.
4- enhance the drug bioavailability
5- maximize preservative efficacy

• The pH of normal tears is ~7.4, but it is more acidic in contact lens

wearers
• Ideally, ophthalmic preparations should be buffered to pH 7.4, but a
compromise is needed to balance solubility, stability, and drug
absorption
44 3- Stabilizers & Antioxidants

• Stabilizers are ingredients added to a formula to decrease the

rate of decomposition of the active ingredients.

• Antioxidants are the principal stabilizers added to some

ophthalmic solutions, primarily those containing epinephrine
and other oxidizable drugs.

Sodium bisulfite or metabisulfite are used in concentration up to

0.3% in epinephrine hydrochloride and bitartrate solutions.

Several antioxidant systems have been developed. These consist of

ascorbic acid and acetyl cysteine, and Sodium thiosulfate.
 45 4- Surfactants

The order of surfactant toxicity is:

anionic > cationic >> nonionic.

•Several nonionic surfactants are used in relatively low concentrations to aid in

dispersing steroids in suspensions and to achieve or to improve solution clarity.

Those principally used are the Sorbitan ether esters of oleic acid (Polysorbate or
Tween 20 and 80),

Nonionic surfactant is a term used to describe active molecules that have no

electric charge.
They are usually not affected by the hardness of the water.

Nonionic surfactant is a combination of alcohols and fatty acids.

46 5- Viscosity-Imparting Agents

• A thickening agent such as methylcellulose is frequently added to the

ophthalmic solution to increase contact time
• Optimal viscosity range: 15 – 25 cP

Polyvinyl alcohol, methylcellulose, hydroxypropyl methylcellulose,

hydroxyethylcellulose, and carbomers are commonly used to increase the
viscosity of ophthalmic solutions and suspensions.

They increase the ocular contact time, thereby decreasing the drainage
rate,increase the mucosadesiveness and increasing drug bioavailablity.

A secondary benefit of the polymer solutions is lubricating effect. the major

commercial viscous vehicles are hydroxypropylmeth;cellulose (isopto) and
polyvinyl alcohol (Liquifilm)
47 6- Vehicles

Ophthalmic drops using purified water USP as the solvent.

Purified water meeting USP standards may be obtained by: distillation,
deionization, or reverse osmosis (RO).

Oils have been used as vehicles for several topical eye drop products that are
extremely sensitive to moisture.

When oils are used as vehicles in ophthalmic fluid , they must be of the highest
purity.

Vegetable oils such as olive oil, castor oil, and sesame oil have been used for
extemporaneous compounding.
These oils are subject to rancidity and therefor must be used carefully.

5/15/2024
48 Ocular bioavailability
• Ocular absorption may be affected by:
– Protein binding
• Normally, tears contain low % of albumin and other proteins, but they are
increased in some disease states
Protein-bound drugs cannot be absorbed by the corneal epithelium
– Drug metabolism (not very significant)
– Lacrimal drainage (decreases residence time)
– Drug solubility
– The cornea contains lipophilic and hydrophilic layers → drugs with both
lipophilic and hydrophilic characteristics permeate more readily
– Residence time of the formulation
49 Topical Eye Drops Packaging
 Eyedrops have been packaged almost entirely in plastic dropper bottles (the Drop-Tainer®
plastic dispenser).
 The main advantage of the Drop-Tainer are:
- convenience of use by the patient
- decreased contamination potential
- lower weight
- lower cost
 The plastic bottle and dispensing tip is made of low-density polyethylene (LDPE) resin,
which provides the necessary flexibility and inertness.
 The cap is made of harder resin than the bottle.
** Advantage of LDPE resin:
- Compatible with a very wide range of drugs
- and formulation components

** Disadvantage of LDPE resin:

- Sorption and permeability characteristics e.g. volatile preservatives such as
chlorobutanol
- Weight loss by water vapor transmission
- LDPE resin is translucent, if the drug is light sensitive, additional package
protection is required (using opacifying agent such as titanium dioxide)
-- LDPE resin sterilized by gamma irradiation or ethylene oxide

50
 51

 A special plastic ophthalmic package made of polypropylene is introduced.

The bottle is filled then sterilized by steam under pressure at 121°c.
 The glass bottle is made sterile by dry-heat or steam autoclave sterilization.
 Amber glass is used for light-sensitive products.
 A few products still remain in glass dropper bottles because of special stability
considerations ( drugs that are sensitive to oxygen or contain permeable
components that are not sufficiently stable in plastic).
 Powder for reconstitutions also use glass containers, owing to their heat-
transfer characteristics, which are necessary during the freeze drying
processes.
 A sterile dropper assembly is usually supplied separately.
52 Administration of eye drops

1. Wash hands thoroughly

2. Shake well (suspensions)
3. Inspect solution for color and clarity
4. Don’t let the dropper touch the eye, eyelid or any other surface
53

B. Semisolid Dosage Forms Ophthalmic Ointments and Gels

54 Ophthalmic ointments
• Compared with ophthalmic solutions, ophthalmic ointments provide extended residence time on
the surface of the eye → increased duration and absorption
• Formulation requirements:
1. The base must not be irritating to the eye and must permit the diffusion of the drug
2. The base should have a softening point close to body temperature, both for comfort and
for drug release
• Most often mixtures of white petrolatum and liquid petrolatum (mineral oil) are used as bases
• Drugs are added as solutions or finely micronized powders
• Ophthalmic ointments must meet USP sterility tests and the test for metal particles
• Terminal sterilization is not generally performed
– Steam sterilization and ethylene oxide are ineffective (cannot penetrate the ointment base)
– Dry heat sterilization affects the chemical and physical stability of the formulation
• Instead, ointment ingredients are separately sterilized and then aseptically combined into a final
product
 55  Ointments Formulation:

-Ointments are used as vehicles for antibiotics, sulfonamides,

antifungals and anti-inflammatories.

-Petrolatum vehicle used as an ocular lubricant to treat dry eye

syndromes.

The ointment vehicle used in ophthalmology is usually a mixture of Mneral oil and
petrolatum base. The mineral oil is added to reduce the melting point and modify
the consistency.

*The chief disadvantages of the use of ophthalmic ointments are their greasy
nature, the blurring of vision produced, imprecise dosing, and difficult self
administration.

. They are most often used as adjunctive night time therapy, while eyedrops
administered during the day.
56

*The anhydrous petrolatum base may be made more miscible with water
through the use of an anhydrous liquid lanolin derivative.

*The carbomer polymeric gel base itself has been used successfully to treat
moderate to severe cases of dry eye.

Ophthalmic ointment must be free from large particles and must meet the
requirements for "leakage" and for "metal particles“

Gels have increased residence time and enhanced bioavailability

Than eye drops.

N.B. Emulsion bases should not be used in the eye owing to ocular
irritation produced by the soaps and surfactants used to form the
Emulsion.
57

 It is suitable for moisture sensitive drugs and has

 longer contact time than drops.
 Chlorobutanol and methyl- and propylparaben are the
most commonly used preservatives in ophthalmic ointments.
58
Ointments Packaging
Ophthalmic ointments are packaged in:

(1) small collapsible tin tube, usually holding 3.5 g of product. The pure tin
tube is compatible with a wide range of drugs in petrolatum-based
ointments.
(2) Aluminum tubes have been used because of their lower cost and as an
alternative should the supply of tin.

(3) Plastic tubes made from flexible LDPE resins have also been considered as
an alternative material.

•Filled tubes may be tested for leakers.

The screw cap is made of polyethylene or polypropylene. The tube can be a
source of metal particles and must be cleaned carefully before sterilization.

(By autoclaving or by ethylene oxide)

59
How to Use Eye Ointments and
Gels Properly?
60

C. Solid Dosage Forms: Ocular Inserts

 61 C. Solid Dosage Forms: Ocular Inserts

 Ophthalmic inserts are defined as sterile solid or semisolid

preparations, with a thin, flexible and multilayered structure,
for insertion in the conjunctival sac.
62

Ophthalmic preparations 5/15/2024

63

 Advantages:
 Increasing contact time and improving bioavailability.
 Providing a prolong drug release and thus a better efficacy.
 Reduction of adverse effects.
 Reduction of the number administrations and thus better
patient compliance.
 64 C. Ocular Inserts Insoluble inserts

 Insoluble insert is a multilayered structure consisting of a drug containing core

surrounded on each side by a layer of copolymer membranes through which the
drug diffuses at a constant rate.
 The rate of drug diffusion is controlled by:
- The polymer composition
- The membrane thickness
- The solubility of the drug

e.g. The Ocusert® Pilo-20 and Pilo-40 Ocular system

- Designed to be placed in the inferior cul-de-sac between the sclera and the eyelid
and to release pilocarpine continuously at a steady rate for 7 days for treatment of
glucoma.

- consists of
- (a) a drug reservoir, pilocarpine (free base), and a carrier material, alginic acid:
- (b) a rate controller ethylene vinyl acetate (EVA) copolymer membrane.
65
66

Advantages of pilocarpine ocuserts over drops :

The ocusert exposes the patient to a lower amount of the drug leading to reduced side
effects
The ocusert provide a continuous control of the intra-ocular pressure
The ocusert is administered only once per week & this will imporve patient compliance
The ocusert contain no preservative so they will be suitable for patients sensitive to
preservatives in opthalmic solutions

Disadvantages of pilocarpine ocuserts:

They are more expensive than drops It may be inconvenient for the patient to retain the
ocusert in the eye for the full 7 days
The ocusert must be checked periodically by the patient to see that the unit is still in
place
67

D. Intraocular Dosage Forms

 68 D. Intraocular Dosage Forms

 They are Ophthalmic products that introduced into the interior structures of
the eye primarily during ocular surgery.
 Requirements for formulation:
1- sterile and pyrogen-free
2- strict control of particulate matter
3- compatible with sensitive internal tissues
4- packaged as preservative-free single dosage
69 1- Irrigating Solutions

 It is a balanced salt solution was developed for hydration and clarity of the cornea
during surgery.
 It contains the five essential ions: sodium, potassium, calcium, magnesium and
chloride.it also contains citrate, acetate ions, and a potential source of bicarbonate.
 It is formulated to be iso osmotic with aqueous humor and has a neutral to slightly
alkaline physiological pH.
 They are required to be preservative- free to prevent toxicity they must be non-
pyrogenic, therefore requiring sterile water for injection (WFI) as a vehicle.
 These irrigating solutions have been developed to be used without the addition of
any drugs or some drugs such as epinephrine are added to the irrigating solution
prior to surgery and used by cataract surgeons.
70
2- Intraocular Injections

The ophthalmologist use available parenteral dosage forms to deliver anti-infective,

corticosteroids, and anesthetic products to achieve higher therapeutic concentrations
intraocular than can ordinarily be achieved by topical or systemic administration.
FDA approved intraocular injections include miotics viscoelastic and an antiviral
agent for intravitreal injection.
71 3- Intravitral Implant

An intravitreal sterile implant containing ganciclovir or antineoplastic agents

is a tablet of ganciclovir with magnesium stearate and is coated drug release
with polyvinyl alcohol and ethylene vinyl acetate polymers such that the
device when surgically implanted in the vitreous cavity release drug over a 5
to 8 months period
72 Drugs used in the eye:

 Miotics e.g. pilocarpine Hcl

 Mydriatics e.g. atropine
 Cycloplegics e.g. atropine
 Anti-inflammatories e.g. corticosteroids
 Anti-infectives (antibiotics, antivirals and antibacterials)
 Anti-glucoma drugs e.g. pilocarpine Hcl
 Surgical adjuncts e.g. irrigating solutions
 Diagnostic drugs e.g. sodiumfluorescein
 Anesthetics e.g. tetracaine
 73

Miotics e.g. pilocarpine Hcl

is used alone or with other medications to treat high pressure inside the eye due
to glaucoma or other eye diseases (e.g., ocular hypertension). Lowering high
pressure inside the eye helps to prevent blindness, vision loss, and nerve damage.
This medication may also be used during certain eye surgeries and to reverse the
effects of drugs used to enlarge the pupil (e.g., during an eye
exam).Pilocarpine works by causing the pupil of the eye to shrink and decreasing
the amount of fluid within the eye.

How to use pilocarpine HCl ophtTo apply eye drops, wash your hands first. To
avoid contamination, be careful not to touch the dropper to any surface or let it
touch your eye.
If you are wearing contact lenses, remove them before using eye drops. Wait at
least 15 minutes before replacing your contact lenses.
74

Contact lenses
75 Contact lenses
• To counsel patients properly, it is important for pharmacists to know the
characteristics and features of the types of contact lenses and the products
available for their care and use
• Contact lenses are classified by their chemical composition and physical
properties as hard, soft, and rigid gas permeable (RGP)

Hard contact lenses

Durable, provide clear vision
Made of a rigid material (polymethylmethacrylate; PMMA)
Cover only a part of the cornea, float on a tear layer
Require an adaptation period
Impermeable to O2 and moisture
76 Soft contact lenses

• More comfortable, more popular

• Cover the entire cornea → Less likely to dislodge spontaneously
• Vision is not as clear as with hard lenses, less durable
• May absorb medication applied to the eye
• Made of hydrophilic cross-linked hydroxyethylmethacrylate (hydrogel)
with high water % → permeable to O2
• Available as daily wear (disposable) or extended wear (up to 30 days)
• Extended wear lenses should be removed every 4-7 days for cleaning
and disinfection
77 Rigid gas permeable (RGP) lenses

• O2 permeable
• Hydrophobic
• Durable
• Good vision clarity
• More comfortable than hard lenses
• Mostly for daily wear (disposable)
78 Care of contact lenses

• Extended wear soft contact lenses:

– Cleaning to remove lipid and protein deposits
– Rinsing
– disinfection
• Hard contact lenses:
– Cleaning to remove debris and deposits
– Soaking in a storage disinfecting solution
– Wetting the lenses prior to insertion to decrease their hydrophobicity
79 Products for soft contact lenses
• Cleaning solutions:
– Surfactant solutions (nonionic detergent, buffer, chelating agent,
preservative)
– Enzymatic cleaners (to remove protein deposits, recommended at least once
a week) – enzyme tablets dissolved in saline or 3% hydrogen peroxide
• Rinsing and storage solutions:
– Isotonic saline buffered to pH 7
– Packaged in aerosol cans or single use vials to avoid the need for
preservatives
• Disinfection solutions:
– Hydrogen peroxide (must be neutralized to prevent eye irritation)
80 Products for hard contact lenses
• Cleaning solutions
• Soaking and storage solutions:
– Contain a disinfectant such as benzalkonium chloride and
disodium edetate
– Overnight soaking is recommended
• Wetting solutions:
– Contain a surfactant to promote lens hydration and provide
cushioning between the lens and the cornea and eyelid
– Also contain a thickening agent, preservatives, and buffering
agents
81 Products for RGP contact lenses

• Similar to hard contact lenses but RGP-specific solutions must be used

• After cleansing, lenses should be rinsed and soaked in a wetting or
soaking solution overnight
• Lenses should be weekly cleaned with enzymatic cleaners similar to soft
contact lenses
82 Clinical considerations in the use of contact lenses

• Soft contact lenses can absorb certain topically administered drugs and
affect their bioavailability
• Ophthalmic suspensions and ointments may cause some vision problems
→ patient should be prescribed an eye solution or stop wearing the lens
during the treatment
• Some drugs administered systemically may cause drug-lens interactions
(discoloration, clouding, ocular inflammation)
• Some drugs have ocular side effects (increased/decreased lacrimation,
ocular edema)
83 Important counseling points for patients

1. Wash hands thoroughly with a nonabrasive soap before and after handling
lenses
2. Do not rub the eyes when the lenses are in place, and if irritation develops,
they should be removed until it subsides
3. Use care products specific to the type of lens used
4. Discard expired cleansers and care products
5. Never use saliva to wet the lens for reinsertion
6. Check the lens for scratches, chips, particles, and discoloration
7. If wearing the lens is causing pain, consult your ophthalmologist
8. Have your eyes examined regularly to ensure that no corneal damage has
occurred due to lens wear
 Thank You
84

With my Best wishes