ocular, skeletal, and periodontal drug delivery - minko

ocular drug delivery

• cornea = protects the front of the eye

• blood-retina barrier = protects the back of the eye

• eye is uniquely shielded from foreign substance penetration by its natural anatomic barriers → makes effect drug delivery to the inside of the eye difficult

dry delivery by eye drops (local, topical)

• limited by inefficient penetration into front of eye

• virtually NO penetration to the back of the eye

systemic medications (oral tablets, IV admin)

limited by inefficient penetration into the back of the eye (blood-retina barrier)

intraocular innjection

circulatory process quickly reduces bioavailability

drug delivery to the eye

• topical medications are frequently impeded in reaching a targeted site due to the eye’s natural protective surface

• in many situations, less than 1% of the medication applied to the surface of the eye will actually reach the disease site

• to achieve sufficient concentration of drug delivered to the back of the eye, medications are frequently administered systemically at very high doses → levels are necessary to overcome the blood-retina barrier than protects the eye from select molecules coming from blood stream

• drug injections into the back of the eye are occasionally used but are quickly removed by the eye’s natural circulatory process, often necessitating frequent injections that can carry toxicity risks

drug elimination from the eye

• the solution instilled as eye drops into the ocular cavity may disappear from the pre-corneal area of the eye by any of a composite of the following routes

  • nasolacrimal drainage

  • tear turnover

  • productive corneal absorption

  • non-productve conjunctival uptake

topical ocular delivery

• traditional dosage forms for delivery of drugs in the eye have been solutions and ointments; however, as a consequence of its function as the visual apparatus, mechanisms are strongly developed for the clearance offering materials from the cornea to preserve visual acuity → presents problems in the development of formulations for ophthalmic therapy

• large proportion of topically applied drug is immediately diluted in the tear film and excess fluid spills over the lid margin and the remainder is rapidly drained into the nasolacrimal duct → proportion of the drug is NOT available for therapeutic action since it binds to the surrounding extraorbital tissues → these processes lead to a typical corneal contact time of about 1-2 mins in humans for all instilled solution and an ocular bioavailability that is <10%

• to optimize ocular drug delivery, following characteristics are required:

  • good corneal penetration

  • prolonged contact time with corneal epithelium

  • simplicity of instillation for patient

  • a non-irritative and comfortable form (system should NOT provoke lacrymation and reflex blinking)

  • appropriate rheological properties

ocular drug delivery: overview

• eye = logical choice for site-specific drug therapy

• eye drops

  • limited by inefficient penetration into the front of the eye

  • virtually NO penetration to the back of the eye

• systemic medications (oral tablets, IV injections)

  • limited by inefficient penetration into the back of the eye

  • required high doses

• drug injections

  • circulatory process quickly reduces bioavailability

• inserts and diffusion controlled systems

  • non-compliance, esp in elderly people

• biodegradable DDS (BDD)

  • BDD systems are placed in the eye at the time of elective surgery

  • BDD systems dissolve as they release the active drug

• ophthalmic gels/hydrogels

• iontophoresis

global ocular drug delivery technology market

• market is mainly topical

• ocular inserts, iontophoresis, intraocular implants, hydrogel systems, others = equal amounts

• in general more ocular drug delivery as years go on

skeletal drug delivery

systemic drug delievry

• high dose of drugs → high systemic toxicity

• bone targeted drug delivery

  • skeletal drug delivery system (SDDS)

  • osteotropic drug delivery system (ODDS)

local drug delivery

• sustained drug release