Mastering Ophthalmic Solutions and Suspensions

Ophthalmic Preparations

• The eye is constantly exposed to the atmosphere, dust, pollutants, allergens, bacteria, and foreign bodies, making ophthalmic preparations necessary to treat various eye conditions.

Definition and Purpose

• Ophthalmic products are specialized dosage forms designed to be instilled onto the external surface of the eye (topical), administered inside (intraocular), or adjacent (periocular) to the eye, or used in conjunction with an ophthalmic device.

Dosage Forms

• Commonly employed ophthalmic dosage forms: solutions, gels, suspensions, ointments, ocular inserts, intravitreal injections, and implants.
• Each dosage form has a specific purpose and duration of action:
  • Solutions: most often used, but relatively low duration of action.
  • Suspensions: slightly longer duration of action.
  • Ointments: even larger duration of action.
  • Gels: used for dry eye conditions, with a shorter duration of action.
  • Gel-forming solutions: increases ease of administration.

Lacrimal System and Retention Time

• The normal volume of tear fluid in the cul-de-sac of the human eye is about 7-8 μL.
• A non-blinking eye can accommodate a maximum of about 30 μL of fluid, while a blinked eye can retain only about 10 μL.
• The capacity of the eye to retain liquid and semisolid preparations is limited, therefore, topical applications are administered in small amounts.

Pharmacological Categories of Drugs

• Anesthetics
• Antimicrobials (antibiotics, antifungals, antivirals)
• Anti-inflammatory
• Astringent
• Beta-adrenergic blockers
• Miotics
• Vasoconstrictors

How to Administer Drops and Ointments

• Wash hands with soap and water before and after administration.
• Use a clean dropper or tube, and do not touch the eye or eyelid with the dropper.
• Tilt the head back, and pull the lower eyelid down to form a pocket.
• Put the drops or ointment in the pocket, and then release the eyelid.
• Blink slowly, and then gently close the eye.

Recommendations and Precautions

• Wash hands well before and after administration.
• Use disposable medical gloves if administering to another person.
• Make sure the dropper or tube is clean and does not touch the eye, eyelid, or other surface.
• Do not use drops or ointments of another person.
• Do not use contact lenses while using eye drops or ointments unless authorized by a doctor.

Patient Counselling

• Inform the patient about the correct number of drops to instill, frequency of application, duration of treatment, and proper storage of the medication.
• Warn the patient about potential side effects, such as transient stinging or burning, foreign body sensation, itching, tearing, decreased vision, and margin crusting.

Contact Lenses

• Contact lenses are small lenses that are placed directly in the eye, resting on the cornea.
• They offer aesthetic advantages and, in some cases, better vision than eyeglasses.
• Types of contact lenses: hard, soft, and rigid gas permeable (RGP).

Pharmaceutical Requirements

• Clarity: ophthalmic solutions must be free from foreign particles.
• Sterility: ophthalmic solutions and suspensions must be sterilized for safe use.
• Isotonicity: the concentration of the solution should be equal to or near that of the tear.
• pH and Buffering: the pH should be close to that of the tear drop.
• Viscosity: the solution should have a suitable thickness.
• Ocular Bioavailability: the solution should be able to release the active ingredient in the eye.

Sterilization

• Sterilization by filtration: the retention of all particulate matter, and the removal of microorganisms.
• Examples of sterilizing filters: sterilization by filtration, and the use of a syringe affixed with a microbial filter.

Preservation

• Preservatives are included in multiple-dose eye solutions to maintain product sterility during use.
• Ideal requirements of preservatives: stability, chemical and physical compatibility, and effectiveness.
• Examples of preservatives: cationic wetting agents, organic mercurials, esters of p-hydroxybenzoic acid, and alcohol substitutes.### Microorganisms and the Cornea
• Pseudomonas aeruginosa can invade an abraded or lacerated cornea, causing ulceration and even blindness
• Combinations of benzalkonium chloride, polymyxin B sulfate, and EDTA can be effective against most Pseudomonas strains
• EDTA makes P. aeruginosa more sensitive to benzalkonium chloride

Preservation and Isotonicity

• Thiomersal is an alternative preservative to benzalkonium chloride, suitable for soft contact lens wearers
• Thiomersal is bacteriostatic and fungistatic at neutral and alkaline pHs, but bactericidal at acidic pH levels
• Solutions with an osmotic pressure equal to that of body fluids (0.9% sodium chloride) are considered isotonic
• Hypotonic solutions have a lower osmotic pressure, while hypertonic solutions have a higher osmotic pressure
• Common tonicity adjusting agents include sodium chloride, boric acid, and dextrose

pH Adjustment and Buffering

• pH adjustment is important to provide comfort to the eye, enhance stability of the formulation, and enhance bioavailability
• Most ophthalmic drugs are weakly acidic and have limited buffer capacity
• Ophthalmic solutions are generally buffered at the pH of maximum stability of the drug(s) they contain

Stabilizers, Antioxidants, and Viscosity

• Stabilizers, such as antioxidants, are added to reduce the rate of decomposition of active ingredients
• Examples of antioxidants include sodium sulfite, sodium bisulfite, and sodium metabisulfite
• Viscosity enhancing agents, such as methylcellulose, hydroxyethylcellulose, and polyvinyl alcohol, help solutions remain in the eye for longer periods

Ocular Bioavailability

• Physiologic factors affecting ocular bioavailability include protein binding, drug metabolism, and lacrimal drainage
• Tears contain enzymes capable of metabolic degradation of drug substances
• Ophthalmic suspensions, gels, and ointments mix with lacrimal fluids less readily than low-viscosity solutions, resulting in longer residence time and enhanced bioavailability

Quality Control and Ophthalmic Inserts

• Compounding pharmacists should check the appearance and clarity, sterility, pH, and volume/weight of ophthalmic preparations
• Ophthalmic inserts are sterile, solid dosage forms designed for insertion into the conjunctival sac
• Examples of ophthalmic inserts include non-erodible inserts (e.g., Ocusert) and erodible inserts (e.g., Lacrisert)

Contact Lenses

• Types of contact lenses include daily wear, extended wear, and disposable wear
• Contact lenses can be categorized as hard, soft, rigid gas permeable (RGP), and daily wear lenses
• Advantages and disadvantages of each type of lens are discussed
• Care of contact lenses involves cleaning, rinsing, disinfecting, and storing the lenses properly

Care of Contact Lenses

• Cleaning solutions, soaking solutions, wetting solutions, and combination solutions are used to care for contact lenses

• Enzymatic cleaners break down protein deposits on soft lenses

• Rinsing and storage solutions are used to rinse and store lenses

• Wetting solutions are used for hard lenses to facilitate hydration and improve tear spreading

• Combination solutions are available for convenience, but may have limited cleaning effectiveness### Medications Affecting Contact Lens Use

• Certain medications administered via other routes can affect tears and interact with contact lenses, causing issues such as:

  • Orange stain (rifampin)
  • Turbidity of the lenses (ribavirin)
  • Ocular inflammation (salicylates)
  • Refractive changes (acetazolamide)

Medications with Ocular Side Effects

• Drugs with anticholinergic effects (e.g., antihistamines, tricyclic antidepressants) can:
  • Decrease tear secretion
  • Cause lens intolerance
  • Damage the eye

Medications Interfering with Contact Lens Use

• Isotretinoin (for severe acne) can induce marked dryness of the eye, interfering with contact lens use during therapy
• Medications that promote excessive tearing (e.g., reserpine) or eye/eyelid edema (e.g., primidone, hydrochlorothiazide, chlorthalidone) may also interfere with lens wear

Ophthalmic Vasoconstrictors

• Can cause dilation of the pupil, especially in contact lens wearers
• Effect lasts 1-4 hours, but is not clinically significant
• FDA recommends informing patients of this side effect on the product label