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 drugs 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 drugs 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

 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 problemhighly efficient at nebulizing: water into fine droplets up to 90% of water contaminants (cause respiratory irritation to chronic lung problems )

INHALATION SOLUTIONS

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 crosscontamination between individuals.

NASAL ROUTE FOR SYSTEMIC EFFECTS

Of current interest to develop a non-oral, nonparenteral 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 (swimmers 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.

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