Unformatted text preview: PHCY 6100-2007 DOSE FORM DESIGN OPHTHALMIC, NASAL AND OTIC PREPARATIONS
OPHTHALMIC PREPARATIONS: aqueous solutions, suspensions, ointments, inserts
applied topically to the eye (for localized effect on the surface or on its interior).
Application is by dropwise, by adding a thin ribbon of preparation to the lid margin, or
by inserting a device for continuous release of drug.
EYE: has limited capacity to retain liquid. Normal volume of tears is 7 L; non-blinking
eye accommodates ~ 30 L; blinking eye, 10 L. Usual drop size is 50 L so much of a
drop is lost. Use multiple drop therapy with few minutes interval. Sometimes, for
serious infections, oral and parenteral therapies are used to attain effective dose of a
Characteristics of Ophthalmics
1. STERILITY: achieved by autoclaving (121°C for 15 min.) whenever possible or by
bacterial filtration (0.2 µm pore size).
Preservation: antibacterial agents are usually added to ensure sterility during
the course of use of preparations for intact corneal membranes (multiple dose
containers). No preservative is added to: preparations used during surgery;
inserts; eye washes used in large quantities on burned or abnormal cornea; any
preparation on single dose containers. Preservatives: benzalkonium chloride, chlorobutanol, phenylmercuric acetate/nitrate, and thimerosal. Most of these agents, in concentrations
tolerated by the eye, are ineffective against some strains of PSEUDOMONAS
AERUGINOSA, which can cause ulceration and blindness. Also, some are
incompatible with certain agents used in ophthalmics. Mixtures of preservatives
and other agents (antibiotics, chelating agents) have proved to be effective
against these strains. Typical examples are Benzalkonium + polymixin B and
Benzalkonium + EDTA.
2. ISOTONICITY: preparations for ophthalmic use must exert the same osmotic
pressure as the lachrymal fluid (corresponding to 0.9% NaCl) for efficacy, safety
and comfort (no burning, tingling, swelling sensation).
o A given volume of a solution of electrolyte (e.g. KCl) will exert a greater osmotic
pressure (due to a greater number of particles) than the same volume of a nonelectrolyte solution (e.g. Dextrose).
o If two liquids have the same osmotic pressure they are called ISOSMOTIC but
a liquid is ISOTONIC only when it has the same osmotic pressure as some body
fluid. Teixeira 1 PHCY 6100-2007 o o
o DOSE FORM DESIGN In ophthalmic preparations, all solutes contribute to the osmotic pressure.
When a combination of drugs is used, each agent's contribution to the tonicity
must be taken in consideration. The sodium chloride equivalent method is the
most popular method used to calculate tonicity of ophthalmic solutions but the
USP provides pre-calculated volumes of sterile water to be added to 1 g of some
common ophthalmic drugs to prepare isotonic solutions.
Hypertonic solutions added to the eye will draw water out of the cells and cause
shrinking (Crenation in blood).
Hypotonic solutions added to the eye will cause water to enter the cells and
they may burst (Hemolysis in blood). 3. BUFFERING: many ophthalmic products require a buffer to maintain stability of
drug, control therapeutic activity and reduce discomfort to the patient. The pH of
lachrymal fluid is 7.4 and some buffering capacity is available at eye level.
USP buffer vehicles for ophthalmics: BORIC ACID vehicle: 1.9 % boric acid solution, pH ~5.0. ISOTONIC PHOSPHATE vehicle: mixture of monobasic and dibasic salts of
phosphate, pH 5.9-8.0.
4. VISCOSITY: due to fast lachrymal drainage, liquids with low viscosity will have
little contact time with the corneal membranes. Thickening agents are frequently
added to ophthalmic solutions and suspensions to help the drug remain in cul-de-sac
and enhance the therapeutic effect. METHYLCELLULOSE and several cellulose
derivatives are largely used as thickening agents in ophthalmics.
5. BIOAVAILABILITY: several factors may affect the ocular bioavailability of drugs.
Protein binding: proteins present in tears (0.6 - 2%) make drug unavailable for
absorption. Also certain diseases increase ocular protein levels (uveitis=
inflammation of the uveal tract of the eye, may lead to visual impairment and
blindness). Drug metabolism: presence of enzymes (lysozyme) in lachrymal fluid may
destroy drug before absorption. Lachrymal drainage: may remove drug too fast and
contact with tissue will be too brief for absorption. Product formulation with
unionized drugs will permeate the cornea easier (greater lipid solubility) than
ionized drugs which will become hydrated. OPHTHALMIC SUSPENSIONS: less used than solutions but may increase the corneal
contact and improve drug action. Same requirements as solutions. Particle size of
suspensoid should be very small and non-irritating to the eyes (no agglomeration upon
storage) Teixeira 2 PHCY 6100-2007 DOSE FORM DESIGN OPHTHALMIC OINTMENTS: manufactured from sterile ingredients or sterilized
after preparation. Provide increased ocular contact time of the drug when compared to
liquid forms. Blurred vision is the main disadvantage.
OPHTHALMIC INSERTS: flexible and 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. OCUSERT® is an insert containing
pilocarpine for glaucoma therapy; LACRISERT® is an insert with a cellulose derivative
for dry eye states. CONTACT LENS PRODUCTS
NASAL PREPARATIONS: solutions (applied as drops, sprays or inhalers) and jellies for
Decongestant (vasoconstrictor) adrenergic agents: tx of rhinitis and sinusitis.
Synthetic Oxytocin: breast feeding
Solutions: isotonic, buffered, and preserved. Frequent and prolonged use cause chronic
edema of nasal mucosa (Rhinitis medicamentosa) also known as "rebound congestion"
(continual stimulus of adrenergic receptors located in nasal canal). Nasal decongestants
are not addictive, the relief they bring is addictive. Use of topical saline provides
psychological assistance for withdrawal of nasal vasoconstrictors.
Inhalers: drugs with high vapor pressure (volatilize slowly). EX: Benzedrex, Amylnitrite
EAR/OTIC/AURAL PREPARATIONS: solutions, suspensions, ointments, placed in ear
Treatment of infections, inflammation, pain: antibiotics, analgesics and
Removal of excessive cerumen (ear wax): mixture of secretions of sweat glands,
sebaceous glands, epithelial cells, hair, dust, foreign bodies which may cause
itching, hearing problems and pain. Preparations for removal of cerumen contain
cerumenolytic surfactants (triethanolamine polypeptide oleate-condensate,
carbamide peroxide) or light mineral oil, vegetable oils or hydrogen peroxide,
which dissolve the cerumen.
*Anhydrous Glycerin and polyethylene glycol (PEG) are commonly used as
vehicles for ear preparations because their hygroscopicity reduces moisture,
bacterial growth and inflammation secretions. Teixeira 3 ...
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