SPECIAL APPLICATION

SOLUTIONS
 OPHTHALMIC DRUG DELiVERY
 Surface or intraocular conditions treated by ophthalmic
preparations:
* bacterial, fungal and viral infections of the eye or eyelids;
*allergic or infectious conjunctivitis or inflammation;
*elevated intraocular pressure and glaucoma
*dry eye due to inadequate production of luids bathing the
eye.
 treating ophthalmic conditions (glaucoma)
-employed: systemic drug use and topical treatments
 normal volume of tear fluid in the cul-de-sac of the human
eye
- 7 to 8 uL.
 OPHTHALMIC DRUG DELiVERY
 capacity of the eye to retain liquid and semisolid preparations is
limited:
- topical applications are administered in small amounts,
(dropwise)
- ointments as a thin ribbon applied to the margin of the eyelid.
 Larger volumes of liquid preparations
- used to flush or bathe the eye.
 dynamics of the lacrimal system:
- short retention time of an ophthalmic solution on the eye surface
- amount of drug absorbed: small fraction of the quantity
administered.

 OPHTHALMIC DRUG DELiVERY

 formulations that extend corneal contact time:

Decreased frequency of dosing
increased ocular retention time
greater bioavailability
achieved by:
gel systems liposomes polymeric drug carriers
ophthalmic suspensions ointments.
 PHARMACOLOGIC CATEGORIES OF
OPHTHALMIC DRUGS
 Anesthetics
 Antibiotic & antimicrobial agents
 Antifungal agents
 Anti-inflammatory agents
 Antiviral agents
 Astringents
 Beta-adrenergic blocking agents
 Miotics and other glaucoma agents
 Mydriatics and cycloplegics
 Protectant and artificial tears
 Vasoconstrictors & ocular decongestants
 PHARMACEUTICAL REQUIREMENTS
 STERILITY AND PRESERVATION
*Ophthalmic solutions and suspensions sterilized for
safe use.
*sterilize ophthalmics in their final containers by
autoclaving (121oC (250oF) for 15 minutes)
-method unacceptable by thermal instability of the
formulation.
-Bacterial filters : alternative with high degree of
efficiency, not as reliable as the autoclave.
- advantage of filtration: removalof all particulate
matter (microbial, dust, fiber) important in the
manufacture and use of ophthalmic solutions.
STERILITY AND PRESERVATION
 maintaining sterility during use:
- antimicrobial preservatives are included
- exception: preparations used during surgery or in the
treatment of traumatized eyes (preservatives irritate the eye)
- preservative free preparations are packaged in single-use
containers.
 antimicrobial preservatives used in ophthalmic solutions and
suspensions:
benzalkonium chloride, benzethonium chloride,
chlorobutanol, phenylmercuric acetate, phenylmercuric
nitrite, thimerosal.
Disadvantages of these preservatives:
- ineffective against some strains of Pseudomonas aeruginosa
- invade an abraded cornea and cause ulceration and even
blindness.
STERILITY AND PRESERVATION

 effective against most strains of Pseudomonas

- mixtures of benzalkonium chloride + polymyxin B
sulfate / disodium EDTA (chelating agent for
metals)
Isotonicity Value
 body fluids (blood & tears):
osmotic pressure corresponding to that of a 0.9% solution of
sodium chloride.
 isosmotic
- osm press = physiologic fluids
- compares osmotic pressure of two liquids that may or may not
be physiologic fluids.
- ex. 0.9% NaCl solution
 Isotonic (equal tone)
- used with reference to a specific body fluid
- limits of an ophthalmic solution in terms of NaCl or its osmotic
equivalent ranging from 0.6 to 2.0% without marked discomfort
to the eye.
Isotonicity Value
 hypotonic
– solutions with a lower osmotic pressure than body fluids
or a 0.9% NaCl solution.
- induce hemolysis of red blood cells or passage of water
from the site of an ophthalmic application → tissues of the
eye
 hypertonic
– solutions having a greater osmotic pressure
- water from the body tissues toward the solution
- cause crenation (shrinking) of blood cells, solution can
draw water in the eye→ site of the topical application

 
BUFFERING
 purposes of adjusting and buffering the pH of
ophthalmic preparation:
- greater comfort to the eye
- renders the formulation more stable
- enhances the aqueous solubility of the drug
- enhances the drug’s bioavailability
- maximizes preservative efficacy
 pH of normal tears - 7.4
- for contact lens wearers - more acidic.
 tears – with some buffer capacity.
BUFFERING
 Ophthalmic drugs
- weakly acidic and weaker buffer capacity
 buffering action of the tears
- neutralizes the ophthalmic solution
- prevents marked discomfort.
 eye tolerate a greater deviation from physiologic pH
toward alkalinity (less discomfort) than acidic range.
 ophthalmic solution for maximum comfort:
- same pH as the tears.
- a compromise pH is selected and maintained by
buffers (greater activity & maintain stability)
VISCOSITY AND THICKENING AGENTS
 PROPERTY OF LIQUIDS RELATED TO THE RESISTANCE
TO FLOW.
 Viscosity: force required to move one plane surface
past another under specified conditions when the
space between is filled by the liquid in question.
- Reciprocal is fluidity.
- optimal in range for ophthalmic solutions: 15 – 25 cp
- changes with temp
- decreases with increasing temperature.
THICKENING AGENTS
 Added in the preparation of ophthalmic solutions:
- to increase the viscosity
- aid in maintaining the drug - contact with the tissues
to enhance therapeutic effectiveness
- thickening agents used:
methylcellulose hydroxypropyl methylcellulose
polyvinyl alcohol
OCULAR BIOAVAILABILITY
 factor in the effectiveness of an applied medication.
 physiologic factors affecting drug’s ocular bioavailability:
protein binding, drug metabolism, lacrimal drainage:
 other factors affecting ocular bioavailability:
- physicochemical characteristics of the drug substance
and product formulation
reason: cornea (membrane barrier) contains both
lipophilic and hydrophilic layers
- permeated effectively by drug substances with
lipophilic and hydrophilic characteristics
ADDITIONAL CONSIDERATIONS
 ophthalmic solutions
- sparkling clear and free of particulate matter for
comfort and safety.
 ophthalmic suspension
- drug particles finely subdivided (micronized), to
minimize eye irritation and/or scratching of the
cornea.
 suspended particles
- not associateD into larger particles upon storage
- easily and uniformly redistributed by gentle shaking
of the container prior to use.
 PACKAGING OPHTHALMIC SOLUTIONS
AND SUSPENSIONS
 packaging:
small glass bottles with separate glass
plastic droppers
soft plastic containers with a fixed built in dropper
 Protected from external contamination
 packaged with an eye cup, cleaned and dried
thoroughly before and after each use.
PROPER ADMINISTRATION OF OPHTHALMIC
SOLUTIONS AND SUSPENSIONS
 WASH THE HANDS THOROUGHLY
 check for chips or cracks
-IF SUPPLIED WITH A SEPARATE DROPPER
 Inspect for color and clarity
 shake suspensions prior to administration to distribute
suspensoid evenly.
 Remove cap of an eyedrop container prior to use and
return after use.
PROPER ADMINISTRATION OF OPHTHALMIC
SOLUTIONS AND SUSPENSIONS
 Dropper not to touch the eye, eyelid, or any other
surface
 correct no. of drops to be instilled
- frequency of application
- duration of treatment
- proper storage of the medication
- side effects specific to the product (stinging or
burning
- foreign body sensation, itching, tearing, decreased
vision, margin crusting, and occasionally a bad
(drug) taste (examples – table)
 NASAL PREPARATIONS

 for intranasal
- contain adrenergic agents
- employed for their decongestant activity on the nasal
mucosa
 Forms:
solution, nose drops or sprays, nasal jellies
 NASAL DECONGESTANT SOLUTIONS
 Aq. prepns. rendered isotonic to nasal fluids (approximately
equivalent to 0.9% NaCl)
-buffered to maintain drugs stability
- normal pH range of nasal fluids (pH 5.5 – 6.5)
- stabilized & preserved as required.
 Uses:
- treatment of rhinitis of the common cold and for vasomotor
and allergic rhinitis including hay fever, and for sinusitis.
 Frequent / prolonged use
- lead to chronic edema of the nasal mucosa (rhinitis
medicamentosa)
 Best used for short periods ( 3 to 5 days)
- not to exceed the recommended dosage & frequency of use.
 INHALATION SOLUTIONS
 Administered by the nasal or oral respiratory route
 administered by:
inhalation aerosols (Pressure packaged) nebulizer
other apparatus
 Effects:For local action (bronchial tree)
systemic effects (lungs)
 administered by inhalation:
gases (oxygen and ether)
finely powdered drug substances
solutions of drugs as fine mists.
 Used as vehicles: Sterile Water for Inhalation, USP
NaCl Inhalation, USP
 INHALATION SOLUTIONS
 To reach the bronchial tree inhaled drug substance or
solution:
particle size few microns in size
 Instruments used:
*Nebulizer - fine particles for inhalation aerosols
*vaporizer - a fine mist of steam volatile medication
added to the water or to a special medication cup, the
medication volatilizes
*heat generated - kills the mold & bacteria that may be in
the water tank
*humidifiers – provides cool mist to the air in a room
– prevents mucous membranes (nose & throat)
from becoming dry & irritated
 INHALATION SOLUTIONS
 Humidifiers:
costly, but less electricity
noisier during operation,
leave a deposition of minerals on woodwork & furniture
cool down a room by 1o to 3o (a problem with young
children)
 Vaporizers & humidifiers – for colds, coughs, & chest congestion
 Vaporizer – produces a fine mist of steam used to humidify a
room
 Ultrasonic humidifiers – noiseless level
pose a health problem-
highly efficient at nebulizing:
water into fine droplets
up to 90% of water contaminants (cause
respiratory irritation to chronic lung problems )
 EXAMPLES OF MEDICATED INHALATION
SOLUTIONS


 
Isoetharine inhalation solution (Bronkosol, Sanofi)
isoproterenol inhalation solution (Isuprel Solution,
Sanofi)
- For bronchial spasms treatment of bronchial asthma
& related conditionsas propellant of aerosols
 INHALANTS
 drugs with high vapor pressure carried by an air
current into the nasal passage
 inhaler:
- device volatile drug is contained & by virtue of its
high vapour pressure are carried by air current into
the nasal passage to exert its effect
- placed in the nostril & vapor inhaled to relieve
nasal congestion
- effective so long as the volatile drug remains
present.
- caps should be tightly closed
Example: propylhexedrine (Benzedrex, Menley &
James Labs)
 AMYL NITRITE INHALANT

Acts as a vasodilator
rapid effects - treatment of
anginal pain
Prepared in sealed glass vials covered
with a protective gauze cloth
 PROPYLHEXEDRINE INHALANT
 Liquid adrenergic (vasoconstrictor)agent that volatilizes
slowly at room temperature

 Uses: relieve nasal congestion due to colds & hayfever

relieve ear block & the pressure pain in air travelers

 Commercial product: Benzedrex Inhaler (Menley & James

Labs)
 PROPER ADMINISTRATION & USE OF
NASAL DROPS & SPRAYS
 Before using the:
* drops
- gently blow the nose & wash hands thoroughly with
soap and water.

*spray
- gently blow the nose to clear the nostrils & wash
hands thoroughly with soap and water.

*remove the plastic cap & to never to shake the plastic

squeeze bottle for use
 PROPER ADMINISTRATION & USE OF
NASAL DROPS & SPRAYS
 Spraying medicine into the nostrils NEVER :
*performed with the head over the edge of a bed
-result in the systemic absorption of the drug rather
than a local effect.
*overuse the product (oxymetazoline & xylometazoline
– rebound congestion for more than 3-5 days)
*share the medicated spray to prevent cross-
contamination between individuals.
 NASAL ROUTE FOR SYSTEMIC EFFECTS
 Of current interest to develop a non-oral, non-
parenteral route for newly developed:
* synthetic biologically active peptides
*polypeptides (insulin -destructed by gastrointestinal
fluids, administered by injection)
 Advantages:
- amenable to the systemic absorption of:
*peptides
*nonpeptide drug molecules, poorly absorbed orally
(scopolamine, hydralazine, progesterone and
propranolol).
 OTIC SOLUTIONS
 ear or aural preparations.
 used with suspensions and ointments
 placed in the ear canal (drops/small amounts)
-removal of excessive cerumen (ear wax)
- treatment of ear infections, inflammation, or
pain.
 CERUMEN-REMOVING SOLUTIONS
 Cerumen
- combination of secretions of the sweat and sebaceous
glands of the external auditory canal.
- formed:
*secretions when dried →sticky semisolid (holds shed
epithelial cells, fallen hair, dust and other foreign
bodies) → ear canal.
- cause itching, pain, impaired hearing and a deterrent
to otologic examination.
- impacted and removal made more difficult and
painful.
 CERUMEN-REMOVING SOLUTIONS
 commonly used agents to soften impacted cerumen:

*light mineral vegetable oils hydrogen peroxide

*solutions of synthetic surfactants:

- triethanolamine polypeptide oleate-condensate,
in propylene glycol (Cerumenex Drops).
- carbamide peroxide in glycerin/propylene glycol
(Debrox Drops) - releases oxygen which
disrupts
the integrity of the impacted wax
ANTI-INFECTIVE, ANTI-INFLAMMATORY &
ANALGESIC EAR PREPARATIONS
 used topically for their anti-infective activity:
chloramphenicol, colistin sulfate, neomycin,
polymyxin B sulfate, and nystatin (combat fungal
infections).
- formulated into ear drops (solutions or suspensions)
in a vehicle of anhydrous glycerin or propylene glycol.
ANTI-INFECTIVE, ANTI-INFLAMMATORY &
ANALGESIC EAR PREPARATIONS
 hygroscopic
- draw moisture from the tissues
- reducing inflammation and diminishing the moisture
available for the life process of the microorganisms
present.
 assist in relieving the pain
 contain analgesic agents as antipyrine and local
anesthetics as lidocaine, dibucaine and benzocaine.
ANTI-INFLAMMATORY EAR PREPARATIONS

 Liquid ear preparations of the anti-inflammatory

agents:
- hydrocortisone and dexamethasone sodium
phosphate
ANTI-INFECTIVE, ANTI-INFLAMMATORY &
ANALGESIC EAR PREPARATIONS
 used to treat otitis externa (swimmer’s ear)
-antibiotic-steroid combinations
-acetic acid (2%) in aluminum acetate solution
-boric acid (2.75%) in isopropyl alcohol
- re-acidify the ear canal and the vehicles serve to
help dry (offending microorganisms - Pseudomonas
aeruginosa, is checked)the ear canal
 ANALGESIC EAR PREPARATIONS
 solutions containing
- analgesic (antipyrine)
- local anesthetic benzocaine
- vehicle of propylene glycol or anhydrous glycerin
(Auralgan Otic Solution)
*hygroscopic vehicles reduce the swelling of tissues
(and thus some pain) and the growth of microorganisms
 commonly employed to relieve the symptoms of acute
otitis media. (examples table)
PROPER ADMINISTRATION & USE OF OTIC
DROPS
 determine how the drops are to be used
 When instilled into the ear, allow to run in deeper,
the earlobe held up and back.
- For a child, the earlobe held down and back
- easier to have someone administer the drops.
END