OPHTHALMIC, NASAL

AND OTIC PREPARATIONS

Prepared by:
Umar Farooq
• Pharmaceutical preparations are applied topically to the
eye to treat surface or intraocular conditions, including
bacterial, fungal, and viral infections of the eye or
eyelids; allergic or infectious conjunctivitis or
inflammation; elevated intraocular pressure and
glaucoma; and dry eye due to inadequate production of
fluids bathing the eye.
• In treating certain ophthalmic conditions, such as
glaucoma, both systemic drug use and topical
treatments may be employed.
• Among the dosage forms used in the topical
treatment of conditions and diseases of the eye are
eye drops (in the form of solutions, suspensions or
emulsions), ointments, gels and inserts.
• The application of medication to the eye or
conjunctiva sac affects the surface of the eye and
underlying tissues as the drug penetrates. The major
route by which drugs enter the eye is simple diffusion
via the cornea. For drugs that are poorly absorbed by
the cornea, the conjunctiva and sclera provide an
alternate route.
• In general, ocular ophthalmic drug penetration is
limited by the short residence time on the surface of
the eye because of rapid removal by tearing and
other natural mechanisms, the small surface area of
the cornea for drug absorption, and the cornea’s
natural resistance to drug penetration.
 Eye Drops
• Drugs which are active at eye or eye surface are widely
administered in the form of Solutions, Emulsion and
Suspension.
• Generally eye drops are used only for anterior segment
disorders as adequate drug concentrations are not
reached in the posterior tissues using this drug delivery
method.
• 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 Percent of the dose is absorbed after
topical administration into the eye..
• Ocular absorption is limited and is only moderately
increased by prolonged ocular contact.
• The reported maximal attainable ocular absorption is
only about 10 Percent of the dose.
Ointments & Gels
• Compared with ophthalmic solutions, ophthalmic
ointments and gels provide extended residence time
on the surface of the eye, increasing the duration of
their surface effects and bioavailability for absorption
into the ocular tissues. Ophthalmic ointments are
cleared from the eye as slowly as 0.5% per minute,
compared with solutions, which can lose up to 16%
of their volume per minute.
• The ointment base selected for an ophthalmic
ointment must not be irritating to the eye and must
permit the diffusion of the medicinal substance
throughout the secretions bathing the eye. Ointment
bases used for ophthalmics, 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 the base in
medicated and unmedicated (lubricating) ophthalmic
ointments. Sometimes a water-miscible agent such as
lanolin is added.
• Medicinal agents are added to an ointment base
either as a solution or as a finely micronized powder.
• The ointment is made uniform and smooth by fine
milling. In addition to the previously stated quality
standards for ointments, ophthalmic ointments must
meet the USP sterility tests and the test for metal
particles in ophthalmic ointments.
• Strict methods of aseptic processing are employed as
each drug and nondrug component is rendered sterile
and then aseptically weighed and incorporated in a
final product that meets the sterility requirement.

• When an antimicrobial preservative is needed, among

those used are methylparaben (0.05%) and
propylparaben (0.01%) combinations, phenylmercuric
acetate (0.0008%), chlorobutanol (0.5%), and
benzalkonium chloride (0.008%).
• The USP test for metal particles is microscopic
examination of a heat-melted ophthalmic ointment.
Detected metal particles are counted and measured
by a calibrated eyepiece micrometer disk.
• The requirements are met if the total number of
particles 50μm or larger from ten product tubes does
not exceed 50 and none of the tube contains more
than eight such particles.
• Ophthalmic ointments typically are packaged in small
aluminum or collapsible plastic tubes holding 3.5 g
(about 0.125oz) of ointment. The tubes, which are
sterilized before being aseptically filled, are fitted
with narrow-gauge tips which permit extrusion and
placement of narrow bands of ointment on the inner
margin of the eyelid, the usual site of application.
• An eye that does not blink can accommodate a
maximum of about 30μL of fluid, but when blinked can
retain only about 10μL. Because of the dynamics of the
lacrimal system, the retention time of an ophthalmic
solution on the eye surface is short, and the amount of
drug absorbed is usually only a small fraction of the
quantity administered. For example, following
administration of pilocarpine ophthalmic solution, the
solution is flushed from the precorneal area within 1 to
2 minutes, resulting in the ocular absorption of less
than 1% of the administered dose. This necessitates
repeated administration of the solution.
• In practice, the isotonicity limits of an ophthalmic
solution in terms of sodium chloride or its osmotic
equivalent may range from 0.6% to 2.0% without
marked discomfort to the eye.
• Boric acid in a concentration of 1.9% produces the
same osmotic pressure as does 0.9% sodium chloride.
• All solutes of an ophthalmic solutions, including the
active and inactive ingredients, contribute to the
osmotic pressure of a solution.
BUFFERING
The pH of an ophthalmic preparation may be adjusted
and buffered for one or more of the following
purposes:
a) for greater comfort to the eye,
b) to render the formulation more stable,
c) to enhance the aqueous solubility of the drug,
d) to enhance the drug’s bioavailability (i.e., by
favoring unionized molecular species), and
e) to maximize preservative efficacy.
• The pH of normal tears is considered to be about 7.4,
• Normally, the buffering action of the tears neutralizes
the ophthalmic solution and thereby prevents
marked discomfort.
• For maximum comfort, an ophthalmic solution should
have the same pH as the tears.
• An isotonic phosphate vehicle is used to achieve the
desired pH (Monobasic sodium phosphate, Dibasic
sodium phosphate)
• Thickening agent is frequently added to increase the
viscosity and thereby aid in maintaining the drug in
contact with the tissues to enhance therapeutic
effectiveness.
• Generally, methylcellulose of 4,000cP is used in
concentrations of 0.25% and the 25cP type at 1%
concentration.
• Hydroxypropyl methylcellulose and polyvinyl alcohol
are also used as thickeners in ophthalmic solutions.
• Occasionally, a 1% solution of methylcellulose without
medication is used as a tear replacement.
• Viscosity for ophthalmic solutions is considered
optimal in the range of 15 to 25cP.
PACKAGING OPHTHALMIC SOLUTIONS AND SUSPENSIONS
• Although a few commercial ophthalmic solutions and
suspensions are packaged in small glass bottles with
separate glass or plastic droppers, most are packaged in
soft plastic containers with a fixed built-in dropper.
• This type of packaging is preferred both to facilitate
administration and to protect the product from external
contamination.
• Ophthalmic solutions and suspensions are commonly
packaged in containers holding 2, 2.5, 5, 10, 15 and 30
mL of product.
• Ophthalmic solutions used as eyewashes are generally
packaged with an eye cup, which should be cleaned and
dried thoroughly before and after each use.
OPHTHALMIC INSERTS
Lacrisert
• Lacrisert (Merck) is a rod-shaped water- soluble form of
hydroxypropyl cellulose. The insert is placed in the inferior
cul-de-sac of the eye once or twice daily for the treatment
of dry eyes. The inserts soften and slowly dissolve,
thickening the precorneal tear film and prolonging the tear
film breakup.
Pilocarpine Insert
• Pilocarpine is available in a membrane- controlled reservoir
system that is used in the treatment of glaucoma.
Pilocarpine is sandwiched between two ethylene vinyl
acetate membranes. It also contains alginic acid, a seaweed
carbohydrate, that serves as a carrier for pilocarpine.
• The small, clear device has a white annular border made of
ethylene vinyl acetate copolymer impregnated with
titanium dioxide (pigment) that makes it easier for the
patient to see.
• The insert is placed in the cul-de-sac, where it will float with
the tears. The pilocarpine will diffuse from the device and
exert its pharmacologic effect.
• The tear fluid penetrates the micro porous membrane,
dissolving the pilocarpine. The release rate of pilocarpine is
in the range of 20 or 40 μg per hour for 4 to 7 days. The
units contain either 5 mg or 11 mg of drug (3.4 or 6.7 mg
drug is released). One advantage to this system is enhanced
compliance, as the patient does not have to remember to
instill the drops and has no blurred vision or slight
discomfort that occurs when applying drops to the eyes.
CONTACT LENSES
• The number of persons wearing contact lenses grows
each year.
• About 87% of these persons utilize soft, hydrogel
lenses while the remainder use rigid lenses (Rigid gas
permeable [RGP]) with varying degrees of oxygen
permeability.
• Over 50% of contact lens wearers use 1- to 2-week
disposable lenses and 15% use extended wear (up to
30 days).
• The three basic types of contact lenses are classified by
their chemical composition and physical properties as
hard, soft, and RGP.
PRODUCTS FOR CONTACT LENSES
Cleaners
• Because of their porous composition, soft lenses tend
to accumulate proteinaceous material that forms a film
on the lens, decreasing clarity and serving as a
potential medium for microbial growth.
• The two main categories of cleaners are surfactants,
which emulsify accumulated oils, lipids, and inorganic
compounds, and enzymatic
cleaners, which break down and
remove protein deposits.
• Surfactant agents are used in a mechanical washing device,
by placing several drops of the solution on the lens surface
and gently rubbing the lens with the thumb and forefinger,
or by placing the lens in the palm of the hand and rubbing
gently with a fingertip (about a 20- to 30-second
procedure). The ingredients in these cleaners usually
include a nonionic detergent, wetting agent, chelating
agent, buffers, and preservatives.
• Enzymatic cleaning is accomplished by soaking the lenses in
a solution prepared from enzyme tablets. This procedure is
recommended at least once a week or twice a month in
conjunction with regular surfactant cleansing. The enzyme
tablets contain papain, pancreatin, or subtilisin, which
causes hydrolysis of protein to peptides and amino acids.
Disinfection and Neutralization
• Disinfection can be accomplished by either of two
methods:
• thermal (heat) or
• chemical (no heat).
• For thermal disinfection, the lenses are placed in a
specially designed heating unit with saline solution. The
solution is heated sufficiently to kill microorganisms,
perhaps for 10 minutes at a minimum of 80°C (176°F).
• The wearer must also ensure that the lenses
have been thoroughly cleaned before using
heat disinfection. Otherwise, heating can
hasten lens deterioration.
• In years past, chemical disinfection was conducted with
products that contained thimerosal in combination with
either chlorhexidine or a quaternary ammonium
compound. Unfortunately, many wearers had
sensitivity reactions, and these products and chemical
disinfection fell into disfavor. The introduction of
hydrogen peroxide systems for chemical disinfection
revitalized this method of disinfection.
• In the past, both methods were equally used; however,
with the introduction of hydrogen peroxide systems for
chemical disinfection, has become more popular.
Rinsing and Storage Solutions

• Saline solutions for soft lenses should have a neutral

pH and be isotonic with human tears, that is, 0.9%
sodium chloride.
• Besides rinsing the lenses, these solutions are used for
storage, because saline maintains their curvature,
diameter, and optical characteristics.
• The solutions also facilitate lens hydration, preventing
the lens from drying out and becoming brittle.
Patients counseling
• Contact lens wearers should wash their hands
thoroughly with a nonabrasive, noncosmetic soap
before and after handling lenses.
• Wearers should not rub the eyes when the lenses are in
place, and if irritation develops, the lenses should be
removed until these symptoms subside.
• Only contact lens care products specifically
recommended for the type of lens worn should be used.
Also, to avoid differences between products of different
manufacturers, it is preferable to use solutions made by
a single manufacturer.
• Cleaning and storing lenses should be performed in the
specific solution for that purpose. The patient should be
instructed to discard cleansers and other lens care
products if the labeled expiration date is exceeded.
• Lenses should not be stored in tap water, nor should saliva
be used to help reinsert a lens into the eye. Saliva is not
sterile and contains numerous microorganisms, including P.
aeruginosa.
• The lens should be inspected for any particulate matter,
particles, warpage, and/or discoloration. The patient must
ensure the lens is cleaned thoroughly and rinsed
thoroughly. Otherwise, these factors can lead to eye
discomfort and irritation.
• When cleaning a lens, the patient should be instructed
to clean it back and forth and not in a circular
direction.
• To avoid the “left-lens syndrome,” the patient should
be instructed to clean the second lens as thoroughly
as the first lens.
• Mascara and pearlized eye shadow should be avoided
by women wearing hard lenses because particles of
these products can get into the eye and cause
irritation, with corneal damage a possibility.
• Aerosol hairsprays should be used before the lens is
inserted and preferably applied in another room,
since airborne particles may attach to the lens during
insertion and cause irritation. Lenses should be
inserted before makeup application because oily
substances on the fingertips can smudge the lenses
when they are handled. For similar reasons, lenses
should be removed before makeup. it is important
that all contact lens wearers have their eyes
examined regularly to make certain that no damage
has occurred.
OTIC PREPARATIONS
Otic Preparation
• From Greek ōtikos; of, relating to, or located near the ear;
auricular.
• Otic preparations are pharmaceutical products (drugs) that
are used inside, outsides, or around the ears to exert
therapeutic effect.
• In general, otic preparation are products applied to or in the
ear to treat conditions of the external and middle ear.
 Ear Physiology
• The auricle is the opening to the ear;
• The ear lobe surrounds the auricle;
• The external auditory canal starts at the auricle and ends at
the tympanic membrane
 Otic Preparations
• Otic preparations are sometimes referred to as ear or aural
preparations.
• Solutions are most frequently used in the ear, with suspensions
and ointments also finding some application.
• Ear preparations are usually placed in the ear canal by drops in
small amounts for removal of excessive cerumen (earwax) or
for treatment of ear infections, inflammation, or pain.
• In cerumen-removing solutions light mineral oil, vegetable
oils, and hydrogen peroxide have been commonly used which
softens impacted cerumen for easy removal.
• Carbamide peroxide in glycerin and propylene glycol may be
used.
 Ear Wax
• The waxy material of the ear is called cerumen, or
commonly known as ear wax.
• Cerumen is formed from the combination of the oily
secretions from the exocrine glands with fatty fluid from
the apocrine glands in the external auditory canal.
• Cerumen contains lysosomes, and enzyme that inhibits
bacterial growth.
• The cerumen helps in the lubrication of the ear canal.
• Cerumen traps dust and other materials from reaching the
inner ear.
• Cerumen can also decrease auditory sounds, thus requiring
removal.
Disorders Facing Human Ear

1. Extrenal Otitis (External)

2. Mastoiditis Acute Otitis Media (Middle)

3. Vestibular Neuronitis (Inner)

1. OTITIS EXTERNA
• Definition: This is a generalized infection involving the
whole skin of the external canal of the ear
• Causes: A common source of the infection is increased
moisture trapped in the ear canal, from baths, showers,
swimming, or moist environments . When water is trapped in
the ear canal, bacteria that normally inhabit the skin and ear
canal multiply, causing infection of the ear canal. Swimmer’s
ear needs to be treated to reduce pain and eliminate any effect
it may have on your hearing, as well as to prevent the spread of
infection..
 CAUSES
Other factors that may contribute to swimmer’s ear include:
• hot, humid climate
• Excessive cleaning of the ear canal with cotton swabs or
anything else
• Contact with certain chemicals such as hair spray or hair dye
(Avoid this by placing cotton balls in your ears when using
these products.)
• Insertion of foreign objects (dust, scratching of the ears,
cotton swabs, fingernails, hearing aids, earplugs)
• Damage to the skin of the ear canal following water irrigation
to remove wax.
• A cut in the skin of the ear canal
• Fungus or bacteria
• Perspiration
SYMPTOMS
• The outer is acutely inflamed and tender.
• It is extremely painful to handle and nothing can be seen of the
interior of the canal without causing the patient acute pain.
• Purulent discharges
• Slight hearing loss
• Drainage
• Fever
• Itchiness
 TREATMENT
• Treatment for the early stages of swimmer’s ear includes careful
cleaning of the ear canal and use of eardrops that inhibit bacterial
or fungal growth and reduce inflammation. Before using any
drops in the ear, it is important to be sure you do not have a
perforated eardrum, Check with your otolaryngologist if you have
ever had a perforated, punctured, or injured eardrum, or if you
have had ear surgery.
• Ear drops - Drops are more easily administered if done by
someone other than the patient.
• The patient should lie down with the affected ear facing upwards.
• Drops should be placed in the ear until the ear is full.
• After drops are administered, the patient should remain lying down for a few
minutes so the drops can be absorbed.
• Topical antibiotics , Analgesics, antipruritics, and antihistamines -
may be indicated.
 OTITIS MEDIA
• It is the inflammation of the middle ear (the cavity between the
eardrum and the inner ear that causes the tubes to close causing
the fluid to become trapped. Bacteria from the back of the nose
travel through the eustachian tube directly into the middle ear
cavity and multiply in the fluid. This tube may become blocked
by a bacterial or viral infection.
• Otitis media can only be detected by examining the ear with an
otoscope. Only by directly looking in the ear and seeing how the
eardrum responds to gentle pressure can the diagnosis be
confirmed. Definition
CAUSES
• Allergy- Studies have shown that food and airborne allergies
can cause otitis media.
• Infection - bacteria to cause this infection are Streptococcus
pneumoniae, Haemophilus influenzae and moraxella
catarrhalis.
• Nutritional deficiency -Vitamin A, zinc and iron deficiencies
are more susceptible to upper respiratory and ear infection.
SYMPTOMS
• Fluid remaining in the middle ear for a long period of time
may result in:
• Severe earache
• Hearing loss
• Tinnitus
• Deafness
• Headache
• Rise in temperature
• Purulent discharge
• Burst of the eardrum.
TREATMENT OF OTITIS MEDIA
Medicine:

• Antibiotic
• Ear drops
• Antihistamine
• Anti-inflammatory
• Anti-Pain
Otic Preparations
• Anti-infective preparations used topically in the ear are
formulated as eardrops (solutions or suspensions) in a vehicle
of anhydrous glycerin or propylene glycol.
• These viscous vehicles permit maximum contact time between
the medication and the tissues of the ear.
• In addition, their hygroscopicity causes them to draw moisture
from the tissues, reducing inflammation and diminishing the
moisture available for the life process of the microorganisms.
• To assist in relieving the pain, a number of anti-infective otic
preparations also contain analgesic agents, such as antipyrine,
and local anesthetics, such as pramoxine hydrochloride and
benzocaine.
• When preservation is required, such agents as chlorobutanol
0.5%, thimerosal 0.01%, and combinations of the parabens are
commonly used.
• Antioxidants, such as sodium bisulfite, and other stabilizers are
also included in otic formulations as required.
• Ear preparations are usually packaged in 5 -15 mL glass or
plastic containers with a dropper.
NASAL PREPARATIONS
 NASAL ROUTE
- medical aspects
• The respiratory tract, which includes the

• nasal mucosa
• hypopharynx
• large airways &
• small airways

• provides a relatively large mucosal surface area of approx. 100

m2 (in normal adult) for drug absorption
Nasal Cavity
 The nasal cavity extends from the nostrils in front to the
posterior nasal apertures or choanae behind

 This is where the nose opens into the nasopharynx

 The nasal vestibule is the area of the nasal cavity lying just
inside the nostril
 Cross-sectional view

a – nasal vestibule d – middle turbinate

b – palate e – superior turbinate (olfactory mucosa)
c – inferior turbinate f – nasopharynx

54
 Site of drug
spray &
absorption

03/10/2009 55
Nasal Septum
 The nasal cavity is divided into right and left halves by the
nasal septum

 The septum is made up of the septal cartilage, the vertical plate

of the ethmoid, and the vomer
Mucous Membrane
 The vestibule is lined with modified skin and has coarse
hairs

 The area above the superior concha is lined with olfactory

mucous membrane and contains nerve endings sensitive to
the reception of smell

 The lower part of the nasal cavity is lined with respiratory

mucous membrane

 A large plexus of veins in the submucous connective tissue is

present in the respiratory region
Mucous Membrane
 The presence of warm blood in the venous plexuses serves to
heat up the inspired air as it enters the respiratory system

 The presence of mucus on the surfaces of the conchae traps

foreign particles and organisms in the inspired air

 These particles are then swallowed and destroyed by gastric

acid
NASAL ROUTE FOR SYSTEMIC EFFECTS
• Nasal preparations may be absorbed, and systemic effects after
the intranasal application of solution are fairly common.
• The adult nasal cavity has about a 20-mL capacity, with a large
surface area (about 180 cm2) for drug absorption.
• The nasal tissue is highly vascularized, providing an attractive
site for rapid and efficient systemic absorption.
• One great advantage to nasal absorption is that it avoids first-
pass metabolism by the liver.
• For some peptides and small molecular compounds, intranasal
bioavailability has been comparable to that of injections.
However, bioavailability decreases as the molecular weight of a
compound increases, and for proteins composed of more than
27 amino acids bioavailability may be low .
• Various pharmaceutical techniques and formulation adjuncts,
such as surface active agents, have been shown to enhance
nasal absorption of large molecules.
• Pharmaceuticals on the market or in various stages of clinical
investigation for nasal delivery include lypressin (Diapid,
Sandoz), oxytocin (Syntocinon, Sandoz), progesterone, insulin,
calcitonin (Miacalcin, Novartis), propranolol, and butorphanol
(Stadol, Mead-Johnson) .
Therapeutic class of drugs for nasal
route

• 2 adrenergic agonists
• Corticosteroids
• Antiviral
• Antibiotics
• Antifungal
• More recently, vaccines
Drugs commonly administered through pulmonary
route include

1. Terbutaline Sulphate - 2 adrenergic agonist

2. Salbutamol - 2 adrenergic agonist

3. Budesonide - corticosteroid

4. Ipratropium Bromide - anticholinergic

5. Sodium Chromoglycate – mast cell stabilizer

DOSAGE FORMS
Liquid drop

Liquid spray/nebulizers

Aerosol

Suspension spray/nebulizers

Gel

Sustained release

65
 Drug concentration

Factors affecting
Vehicle of drug delivery
drug absorption
Mucosal contact time

Degree of drug’s ionization

pH of the absorption site

Size of the drug molecule

Relative lipid solubility

66
 NASAL PREPARATIONS
• Most nasal preparations are solutions or suspensions
administered by drops or as a fine mist.
• Most of these preparations are in solution form and are
administered as nose drops or sprays.
• Nasal decongestant solutions are employed in the
treatment of rhinitis of the common cold.
• Most nasal decongestant solutions are aqueous,
rendered isotonic to nasal fluids (approximately
equivalent to 0.9% sodium chloride), buffered to
maintain drug stability while approximating the
normal pH range of the nasal fluids (pH 5.5 to 6.5),
and stabilized and preserved as required. The
antimicrobial preservatives are the same as those
used in ophthalmic solutions.
• The concentration of adrenergic agent in most nasal
decongestant solutions is quite low, ranging from about 0.05%
to 1.0%.
• Most solutions for nasal use are packaged in dropper bottles
or in plastic spray bottles, usually containing 15 to 30 mL of
medication.
• Inhalations are drugs or solutions of drugs administered by
the nasal or oral respiratory route.
• The drugs may be administered for local action on the
bronchial tree or for systemic effects through absorption from
the lungs.
• Certain gases, such as oxygen and ether, are administered by
inhalation, as are finely powdered drug substances and
solutions of drugs administered as fine mists.
• Sterile Water for Inhalation, USP, and Sodium Chloride
Inhalation, USP, may be used as vehicles for inhalation
solutions.
• A widely used instrument capable of
producing fine particles for inhalation
therapy is the nebulizer. This apparatus
contains an atomizing unit in a bulbous
glass chamber.
• A rubber bulb at the end of the apparatus
is depressed and the medicated solution is
drawn up a narrow glass tube and broken
into fine particles by the passing
airstream. The particles produced range
between 0.5 and 5 μm. The larger, heavier
droplets of the mist do not exit the
apparatus but fall back into the reservoir
of medicated liquid. The lighter particles
do escape with the airstream and are
inhaled by the patient.
• Inhalants are drugs or combinations of drugs
that by virtue of their high vapor pressure can
be carried by an air current into the nasal
passage, where they exert their effect. The
device that holds the drug or drugs and from
which they are administered is an inhaler.
• For instance, propylhexedrine (Benzedrex,
Menley & James Labs) is a liquid that volatilizes
slowly at room temperature. The inhaler is
placed in the nostril and vapor inhaled to relieve
nasal congestion. The inhalers are effective so
long as the volatile drug remains present. To
ensure that the drug does not escape during
periods of nonuse, the caps on the inhalers
should be tightly closed.