Ophthalmic Drug Delivery and Dosage Forms

Ophthalmic Drug Delivery

• The primary goal of ophthalmic drugs is local treatment, not systemic absorption. Absorption's significance depends on drug potency and strength.

• Systemic absorption pathways include:

  • Nasolacrimal drainage: Drops drain through the nasal cavity.
  • Nasal structures: Absorption in the nasal cavity, nasopharynx, and lacrimal sac is possible, including absorption through mixing with saliva.
  • Gastrointestinal tract: Swallowed drugs are absorbed.
  • Conjunctival absorption: Rich blood supply allows for more permeable absorption.
  • Trabecular meshwork: Drainage through this meshwork allows drugs to enter the bloodstream.

• Over 50% of ophthalmic drugs can be systemically absorbed. Drugs absorbed via the GI tract bypass the hepatic first-pass effect.

Dosage Form Considerations

• Sterility: Crucial for ophthalmic products, similar to injectable drugs. Contamination can lead to serious consequences, including blindness.
• Pseudomonas aeruginosa is a significant corneal ulcer-causing organism.
• Sterility testing is mandated for commercially manufactured ophthalmic medications.
• Antimicrobial preservatives are necessary in multi-dose eye drops for sterility maintenance; single-use drops typically don't need these preservatives.

Preservatives

• Benzalkonium Chloride (BAK): Is the most commonly used preservative, effective against Pseudomonas aeruginosa, but can damage corneal epithelium at high concentrations.
• Alternatives include polyquad (polyquaternium 1), which is less sensitizing, and thimerosal.
• Oxidizing agents like sodium perborate are newer and act via oxidation of microbes.

pH and Osmolarity

• Ideal pH for ophthalmic products is around 6.6-7.8, matching tear film pH.
• Buffers (acetate, phosphate, citrate, borate) help maintain product pH stability, solubility, and patient comfort.
• Maintaining isotonicity (300mOsm/kg) like tears is crucial for patient comfort, although some products are intentionally hypertonic. (eg 5% NaCl)
• Viscosity Modifiers: Viscosity affects residence time and drug diffusion; increased viscosity can cause blurred vision, while prolonged contact and reduced drainage are benefits. (eg glycerin, cellulose derivatives, polyvinyl alcohol, polyethylene glycols (PEGs))

Ophthalmic Formulations

• Solutions: Most common form, involving dissolving the drug and excipients, followed by sterilization (heat or 0.2 micron membrane filtration).
• Suspensions: Finely micronized particles for minimized irritation and improved dissolution. Used for poorly soluble drugs or to enhance drug stability.
• Emulsions: Less common, employ lipophilic drugs dissolved in oil phase and emulsifiers for stabilization.
• Ointments/Gels: Prolonged contact time, commonly petrolatum-based ointments that can be sterilized. Gels use gelling agents like carbomers and cellulose derivatives to achieve extended contact.

Administration

• Wash hands, tilt head back, and pull down lower eyelid to create a pouch.
• Instill one drop precisely into the conjunctival sac and keep eye closed for 30 seconds.
• Avoid rubbing, wiping, or squeezing the eye. Replace the dropper tip cap without touching it.
• Consider waiting at least five minutes between consecutive drops.