GT Kulkarni

Department of Pharmaceutical Technology MIET, Meerut

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

Human eye

Diameter of 23 mm Three layers

Outermost coat : the clear, transparent cornea and the

white, opaque sclera Middle layer : the iris anteriorly, the choroid posteriorly, and the ciliary body at the intermediate part Inner layer : retina (extension of CNS)

Fig. 3. Cross-sectional view of the eye.

Cornea

Epithelium-stroma-epithelium (fat-water-fat structure) Oil-water partition coefficient Aqueous humor

Fill the anterior and posterior chamber of eye Secrete from blood through epithelium of the ciliary

body Transport from the posterior to the anterior chamber and escape through Schlemms canal

Vitreous humor
Diffuse through the vitreous body and escape from the

eye through the uveo-scleral route

Fig. 4. Corneal cross-section.

Fig. 5. Structural detail of the retina.

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

Precorneal factor

Available instilled or applied dose to exert pharmacologic effect Effect of tear production and instilled fluid drainage Protein binding and metabolism Tear evaporation Nonproductive absorption/adsorption

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 Penetration to the corneal epithelium Tear dilution and washout Suck-back contamination Benzalkonium chloride, thimerosal, chlorobutanol

Topically instilled drug

Preservatives

Ocusert by Alza

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)

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) Ophthalmic prodrug Dipivalylepinephrine (Dipivefrin) Lipophilic increase in corneal absorption Esterase within cornea and aqueous humor Continuous delivery system based upon the osmotic property Thin flat layer, contoured three-dimensional unit Conform to the supratarsal space of the upper cul-de-sac Delivery of diethylcarbamazine in ocular onchocerciasis

Topically applied peptides

Via the blood vessels in the conjunctival mucosa [D-ala2]met-enkephalinamide Prolonged by increasing the viscosity Prevent the peptidase-mediated degradation of peptide in the corneal epithelium

Advantages of the nasal and ocular routes of administration

Rapid absorption Ease of administration Good local tolerance Application of peptides Reducing side effects Treatment of infants and children

Nasal spray formulation

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) The need for a predetermined profile of drug delivery over a prolonged period of days, weeks, or months (e.g., acute corneal infections, acute-becoming chronic inflammation, and corneal graft rejection episodes) Long-continued low dosage for therapy or prophylaxis (e.g., for prevention of corneal graft rejection, prevention of recrudescence of inflammation, and prevention of , or recurrence of, herpetic disease)