Ophthalmic, Nasal and Otic

preparations
 Ophthalmic preparations
• 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.
• The normal volume of tear fluid of the human eye is
about 7 to 8 μL. An eye that does not blink can
accommodate a maximum of about 30 μL of fluid,
but when blinked can retain only about 10 μL.
• Because the capacity of the eye to retain liquid and
semisolid preparations is limited, topical applications
are administered in small amounts, liquids dropwise,
and ointments as a thin ribbon applied to the margin
of the eyelid. Larger volumes of liquid preparations
may be used to flush or bathe the eye.
• 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.
• This necessitates repeated administration of the
solution. Decreased frequency of dosing, increased
ocular retention time, and greater bioavailability are
achieved by formulations that extend corneal contact
time, such as gel systems, liposomes, polymeric drug
carriers and ophthalmic suspensions and ointments.
 PHARMACOLOGIC CATEGORIES OF
OPHTHALMIC DRUGS
• Anesthetics: Topical anesthetics such as tetracaine,
cocaine, and proparacaine, are employed to provide
pain relief preoperatively, postoperatively, for
ophthalmic trauma, and during ophthalmic
examination.
• Antibiotic and antimicrobial agents: systemically and
locally to combat ophthalmic infection. Among the
agents used topically are azithromycin, gentamicin
sulfate, sodium sulfacetamide, ciprofloxacin
hydrochloride, ofloxacin, polymyxin B-bacitracin, and
tobramycin
• Antifungal agents: amphotericin B
• Anti inflammatory agents: Used to treat
inflammation of the eye, as allergic
conjunctivitis. Among the topical anti-infl
ammatory steroidal agents are fl
uorometholone, prednisolone, and
dexamethasone salts.
• Antiviral agents: trifluridine, ganciclovir, and
vidarabine
• Astringents: Used in the treatment of conjunctivitis.
Zinc sulfate is a commonly used astringent in
ophthalmic solutions.
• Beta-adrenergic blocking agents: timolol maleate are
used topically in the treatment of intraocular
pressure
• Miotics: treatment of glaucoma
• Mydriatics: Mydriatics allow examination of the
fundus by dilating the pupil.
• Protectants and Artificial tears: Solutions
Protectants and artificial tears employed as artificial
tears or as contact lens fluids to lubricate the eye
contain agents such as carboxymethyl cellulose,
methylcellulose, hydroxypropyl methylcellulose, and
polyvinyl alcohol.
 PHARMACEUTICAL REQUIREMENTS
• The preparation of solutions and suspensions for
ophthalmic use requires special consideration with
regard to sterility, preservation, isotonicity, buffering,
viscosity, ocular bioavailability, and packaging.
 STERILITY AND PRESERVATION
• Ophthalmic solutions and suspensions must
be sterilized for safe use. Although it is
preferable to sterilize ophthalmics in their fi
nal containers by autoclaving at 121°C (250°F)
for 15 minutes, this method sometimes is
precluded by thermal instability of the
formulation.
• As an alternative, bacterial filters may be used.
Although bacterial filters work with a high
degree of efficiency, they are not as reliable as
the autoclave. However, because fi nal
product testing is used to validate the absence
of microbes, sterility may be ensured by either
method.
• One advantage of filtration is the retention of
all particulate matter (microbial, dust, fiber),
the removal of which has substantial
importance in the manufacture and use of
ophthalmic solutions.
• To maintain sterility during use, antimicrobial
preservatives generally are included in
ophthalmic formulations; an exception is for
preparations to be used during surgery or in
the treatment of traumatized eyes because
some preservatives irritate the eye. These
preservative-free preparations are packaged in
single-use containers.
 ISOTONICITY VALUE
• Body fluids, including blood and tears, have an
osmotic pressure corresponding to that of a
0.9% solution of sodium chloride. Thus, a 0.9%
sodium chloride solution is said to be
isosmotic, or having an osmotic pressure
equal to that of physiologic fluids.
• The term isotonic, meaning equal tone, is
commonly used interchangeably with
isosmotic, although it is correctly used only
with reference to a specific body fluid,
whereas isosmotic is a physicochemical term
comparing the osmotic pressure of two liquids
that may or may not be physiologic fluids.
• 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. Sodium chloride itself does not
have to be used to establish a solution’s
osmotic pressure. Boric acid in a concentration
of 1.9% produces the same osmotic pressure
as does 0.9% sodium chloride.
 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, but it varies; for example, it is more
acidic in contact lens wearers.
• Tears have some buffer capacity. The
introduction of a medicated solution into the
eye stimulates the flow of tears, which
attempts to neutralize any excess hydrogen or
hydroxyl ions introduced with the solution.
• Most drugs used ophthalmically are weakly
acidic and have only weak buffer capacity.
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.
 VISCOSITY AND THICKENING AGENTS
• In the preparation of ophthalmic solutions, a
suitable grade of methylcellulose or other
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.
• E.g. methyl cellulose, hydroxy methyl propyl
cellulose, polyvinyl alcohol.
• Viscosity for ophthalmic solutions is
considered optimal in the range of 15 to 25 cP.
 OCULAR BIOAVAILABILITY
• Ocular bioavailability is an important factor in
the effectiveness of an applied medication.
Physiologic factors that can affect a drug’s
ocular bioavailability include protein binding,
drug metabolism, and lacrimal drainage.
• In addition to physiologic factors affecting
ocular bioavailability, other factors, such as
the physicochemical characteristics of the
drug substance and product formulation, are
important. Because the cornea is a membrane
barrier containing both lipophilic and
hydrophilic layers, it is permeated most
effectively by drug substances having both
lipophilic and hydrophilic characteristics.
• ophthalmic suspensions, gels, and ointments
mix with lacrimal fluids less readily than do
low-viscosity solutions and so remain longer,
enhancing drug activity
 ADDITIONAL CONSIDERATIONS
• Ophthalmic solutions must be sparkling clear
and free of all particulate matter for comfort
and safety.
 PACKAGING
• 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
 Proper administration
• To instill eyedrops, the person should tilt the head
back and with the index finger of the free hand gently
pull downward the lower eyelid of the affected eye to
form a pocket or cup. While looking up, and without
touching the dropper to the eye, the prescribed
number of drops should be instilled into the formed
pocket. The lower eyelid should be released and the
eye closed to allow the medication to spread over the
eye. The eye should be held closed, preferably for a
full minute, without blinking, rubbing, or wiping.
 NASAL PREPARATIONS
• Most preparations intended for intranasal use
contain adrenergic agents and are employed
for their decongestant activity on the nasal
mucosa.
• Most of these preparations are in solution
form and are administered as nose drops or
sprays; however, a few are available as jellies.
 NASAL DECONGESTANT SOLUTIONS
• Nasal decongestant solutions are employed in
the treatment of rhinitis of the common cold
and allergic rhinitis.
• 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.
• Most solutions for nasal use are packaged in
dropper bottles or in plastic spray bottles,
usually containing 15 to 30 mL of medication.
• The products should be determined to be
stable in the container and the package tightly
closed while not in use. The patient should be
advised to discard the solution if it becomes
discolored and/or contains precipitated matter
 INHALATION SOLUTIONS
• 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.
• Example: nebulizers
• used to relieve bronchial spasms of bronchial
asthma and related conditions.
 PROPER ADMINISTRATION AND USE OF
NASAL DROPS AND SPRAYS
• To minimize the possibility of contamination,
the pharmacist should point out to the patient
that the nasal product should be used by one
person only and kept out of the reach of
children.
• Before using the drops, the patient should be
advised to blow the nose gently and wash the
hands thoroughly with soap and water. For
maximum penetration with drops, a patient
should lie down on a flat surface, such as a
bed, hanging the head over the edge, and
tilting the head back as far as comfortable.
• The prescribed number of drops are then
gently placed in the nostrils, and to allow the
medication to spread in the nose, the patient
should remain in this position for a few
minutes. After this, the dropper should be
replaced in the bottle and tightened.
• Before using the spray, the patient should
gently blow the nose to clear the nostrils and
wash the hands thoroughly with soap and
water. The patient should be told not to shake
the plastic squeeze bottle but be sure to
remove the plastic cap.
• While holding the head upright, the patient
should insert the nose piece into the nostril,
pointing it slightly backward, and close the
other nostril with one finger. The patient
should then spray the prescribed or
recommended amount, squeezing the bottle
sharply.
 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.
CERUMEN-REMOVING SOLUTIONS
• Cerumen is a combination of the secretions of
the sweat and sebaceous glands of the
external auditory canal.
• The secretions, if allowed to dry, form a sticky
semisolid that holds shed epithelial cells,
fallen hair, dust, and other foreign bodies that
make their way into the ear canal. Excessive
accumulation of cerumen in the ear may
cause itching, pain, and impaired hearing.
• If not removed periodically, the cerumen may
become impacted and its removal made more
difficult and painful.
• Through the years, light mineral oil, vegetable
oils, and hydrogen peroxide have been
commonly used agents to soften impacted
cerumen for its removal. Recently, solutions of
synthetic surfactants have been developed for
their ability to remove earwax.
• On contact with the cerumen, the carbamide
peroxide releases oxygen, which disrupts the
integrity of the impacted wax, allowing its
easy removal.
 ANTI-INFECTIVE, ANTI-INFLAMMATORY, AND
ANALGESIC EAR PREPARATIONS
• Drugs used topically in the ear for their anti-
infective activity include such agents as ciprofl
oxacin,ofloxacin, polymyxin B sulfate, and
nystatin, the latter agent used to combat
fungal infections. These agents are formulated
into eardrops (solutions or suspensions) in a
vehicle of anhydrous glycerin or propylene
glycol.
• Liquid ear preparations of the anti-infl
ammatory agents hydrocortisone and
dexamethasone sodium phosphate are
prescribed for their effects against the
swelling and inflammation that frequently
accompany allergic and irritative
manifestations of the ear and for the infl
ammation and pruritus that sometimes follow
treatment of ear infections.
• Pain in the ear frequently accompanies ear
infection or inflamed or swollen ear tissue.
Because the ear canal is so narrow, even a
slight inflammation can cause intense pain and
discomfort. Topical analgesic agents generally
are employed together with internally
administered analgesics, such as aspirin, and
other agents, such as anti-infectives, to
combat the cause of the problem.
PROPER ADMINISTRATION AND USE OF OTIC DROPS

• Cerumen removal usually involves placing the

otic solution in the ear canal with the patient’s
head tilted at a 45° angle, inserting a cotton
plug to retain the medication in the ear for 15
to 30 minutes, followed by gentle flushing of
the ear canal with lukewarm water using a soft
rubber ear syringe.
• Drops intended to treat external otitis
infection are intended to be instilled and left
in the ear.
• When instilled into the ear, to allow the drops
to run in deeper, the earlobe should be held
up and back. For a child, the earlobe should be
held gently down and back.