Ocular Drug Delivery Srinivasulu reddy

Ocular Drug Delivery Introduction Ophthalmic preparation Applied topically to the cornea, or instilled in the space between the eyeball and lower eyelid Solution Dilute with tear and wash away through lacrimal apparatus Administer at frequent intervals Suspension Longer contact time Irritation potential due to the particle size of drug Ointment Longer contact time and greater storage stability Producing film over the eye and blurring vision

Controlled delivery system Release at a constant rate for a long time Enhanced corneal absorption Drug with not serious side effect or tolerate by the patient

Distribution and disposition of drugs Precorneal area The cornea The interior of eye Determinant in drug disposition kinetics Binding to aqueous humor and tissue Aqueous flow and turnover Partitioning into and binding within tissues Distribution equilibria

Topical dosage forms Solution Straightforward to make, filter and sterilize Suspension Drug for treatment of inflammatory disease Ointment Oil-stable microbial filter : filter and sterile Amorphous group Topically instilled drug Penetration to the corneal epithelium Tear dilution and washout Preservatives Suck-back contamination Benzalkonium chloride, thimerosal, chlorobutanol

C. Examples of Ocular Drug Delivery Systems Ocusert Pilocarpine, a parasympathomimetic agent for glaucoma Act on target organs in the iris, ciliary body and trabecular meshwork Ethylene-vinylacetate copolymer Carrier for pilocarpine : alginic acid in the core of Ocusert White annular border :EVA membrane with titanium dioxide (pigment) (easy for patient to visualize)

Ocusert collagen shields hydrogel lenses cyclodextrins

Fig. 6. Schematic diagram of the Occusert.

Lacrisert by Merck Patients with dry eyes (keratitis sicca) A substitute for artificial tears Placed in the conjunctival sac and softens within 1 h and completely dissolves within 14 to 18 h Stabilize and thicken the precorneal tear film and prolong the tear film break-up time Ophthalmic gel for pilocarpine Poloxamer 407 (low viscosity, optical clearity, mucomimetic property) onchocerciasis

Ocular indication of controlled-release systems Short, topical ocular half-life (e.g., heparin for ligneous disease) Small, topical ocular, therapeutic index (e.g., pilocarpine for chronic open-angle glaucoma, possibly nucleside, antiviral) Systemic side effects (e.g., timolol for glaucoma and cyclosporin A for graft rejection) Need for combination therapy (e.g., cromoglycate and corticosteroid for asthma and allergies)

D. Conclusion and Future Outlook Advantages of the ocular routes of administration Rapid absorption Ease of administration Good local tolerance

Drug Delivery - Posterior Segment Eye Disease topical, Systemic intraocular periocular (including subconjunctival, sub- Tenon’s, and retrobulbar).

less than 5% of a topically applied drug permeates the cornea and reaches intraocular tissues. SYSTEMIC administration needs more amount of doses to be concentrated in the eye to reach its therapeutic levels.so this aproach may leads to other complications (adverse and side effects)

An intravitreal injection provides the most direct approach to delivering drugs to the tissues of the posterior segment, and therapeutic tissue drug levels can be achieved. Intravitreal injections, however, have the inherent potential side effects of retinal detachment, hemorrhage,endophthalmitis, and cataract.

Vitrasert implant devices, microspheres, and liposomes, are exciting new modalities of drug delivery that offer effective treatment of visually devastating diseases. The devices, however, do require intraocular surgery, must be replaced periodically, and have potential side effects similar to those associated with intravitreal injection.

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