occular drug delivery system

occular control

1. ocular drug delivery system Submitted by: Pratiksha Srivastava M.Pharm (1 st year) Galgotias university

2. Introduction:- Ocular administration of drug is primarily associated with the need to treat ophthalmic diseases. Meant for local therapy and not for systemic action. Applied topically to the cornea , or instilled in the space between the eyeball and lower eyelid

3. Anatomy of the Eye

4. COMPOSITION OF EYE Water - 98% Solid -1.8% Organic element – Protein - 0.67% Sugar - 0.65% NaCl - 0.66% Other mineral element sodium, potassium and ammonia - 0.79%.

5. DRUG IN TEAR FLUID Ocular Absorption (5% of the dose) Systemic Absorption (50-100% of the dose) Major Routes: -Conjuctiva of eye -Nose Minor Routes: -Lacrimal Drainage -Pharynx -Aqueous Humor -Inner Ocular Tissues Corneal Route: -Primary Route. -Small Lipophilic Drugs. Conjunctival and Sclera Route: - Secondary Route. -Large Hydrophilic Drugs. Aqueous Humor Ocular Tissue Elimination MECHANISM OF OCCULAR DRUG ABSORPTION 5

6. Ideal characteristic Sterility Isotonicity : e.g. : 1.9% boric acid, 0.9% NaCl Buffer/pH adjustment Less drainage tendency Minimum protein binding

7. OCULAR DELIVERY SYSTEMS CONVENTIONAL VESICULAR CONTROL RELEASE PARTICULATE SOLUTION SUSPENTION EMULSION OINTMENT INSERT GELS IMPLANTS IONTOPHORESIS DENDRIMER MICROEMULSION NANOSUSPENSION MICRONEEDLE MUCOADHESIVE POLYMERS 7 MICROPARTICLES NANOPARTICLES LIPOSOMES NIOSOMES DISCOMES CLASSIFICATION OF OCDDS

8. Conventional EYE DROPS: Drugs which are active at eye or eye surface are widely administered in the form of Solutions, Emulsion and Suspension. Various properties of eye drops like hydrogen ion concentration, viscosity and instilled volume can influence retention of a solution in the eye. Less than 5 % of the dose is absorbed after topical administration into the eye. The dose is mostly absorbed to the systemic blood circulation via the conjunctival and nasal blood vessels.

9. Advantages And Disadvantages Of Eye Drops: Dosage form Advantages Disadvantages Solutions Convenience Usually do not interfere with vision of patient. Rapid precorneal elimination. Non sustained action. To be Administered at frequent intervals. Suspension Patient compliance. Best for drug with slow dissolution. Longer contact time Drug properties decide performance loss of both solutions and suspended particles. Irritation potential due to the particle size of the drug. Emulsion Prolonged release of drug from vehicle Blurred vision. patient non compliance.

10. Ointment: Prolongation of drug contact time with the external ocular surface can be achieved using ophthalmic ointment vehicle . 10

11. Advantages: Longer contact time and greater storage stability. Flexibility in drug choice. Improved drug stability. Disadvantages: Sticking of eyes lids. Blurred vision. Poor patient compliance. Matting of eyelids.

12. Vesicular: liposomes :- Liposomes are biocompatible and biodegradable lipid vesicles made up of natural lipids and about 25 –100 nm in diameter. They are having an intimate contact with the corneal and conjunctival surfaces which is desirable for drugs that are poorly absorbed, the drugs with low partition coefficient, poor solubility or those with medium to high molecular weights and thus increases the probability of ocular drug absorption. Vesicle composed of phospholipid bilayer enclosing aqueous compartment in alternate fashion. It is Biodegradable, Non-toxic in nature.

13. ADVANTAGES Drugs delivered intact to various body tissues. Liposomes can be used for both hydrophilic and hydrophobic drug. Possibility of targeting and decrease drug toxicity. The size, charge and other characteristics can be altered according to drug and desired tissue. DISADVANTAGES They need many modification for drug delivery to special organs . Stability problem and oxidative degradation. Requires special packaging and storing facility . Costly.

14. Niosomes and Discomes They are non toxic and do not require special handling techniques: Niosomes are nonionic surfactant vesicles that have potential applications in the delivery of hydrophobic or amphiphilic drugs. Discomes act as potential drug delivery carriers as they released drug in a sustained manner at the ocular site.

15. Advantages: The vesicles can act as a depot to release the drug slowly and offer a controlled release. They are osmotically active and stable. They increase the stability of the entrapped drug. Improves therapeutic performance of the drug by protecting it from the biological environment and restricting effects to target cells, thereby reducing the clearance of the drug.

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17. Non erodible inserts: OCUSERT: The Ocusert therapeutic system is a flat, flexible, elliptical device designed to be placed in the inferior cul-de-sac between the sclera and the eyelid and to release Pilocarpine continuously at a steady rate for 7 days. The device consists of 3 layers. 1. Outer layer - ethylene vinyl acetate copolymer layer. 2. Inner Core - Pilocarpine gelled with alginate main polymer. 3. A retaining ring - of EVA impregnated with titanium dioxide.

18. ADVANTAGES Reduced local side effects and toxicity. Around the clock control of drug. Improved compliance. DISADVANTAGES Retention in the eye for the full 7 days. Periodical check of unit. Replacement of contaminated unit Expensive.

19. Contact lens: Contact lenses can be a way of providing extended release of drugs into the eye. Conventional hydrogel soft contact lenses have the ability to absorb some drugs and release them into the post lens lachrymal fluid, minimizing clearance through the conjunctiva. Their ability to be a drug reservoir strongly depends on the water content and thickness of the lens, the molecular weight of the drug, the concentration of the drug loading solution and the time the lens remains in it.

20. Erodible inserts: The solid inserts absorb the aqueous tear fluid and gradually erode or disintegrate. The drug is slowly leached from the hydrophilic matrix. They quickly lose their solid integrity and are squeezed out of the eye with eye movement and blinking. Do not have to be removed at the end of their use.

21. LACRISERTS Sterile rod shaped device made up of hydroxyl propyl cellulose without any preservative. For the treatment of dry eye syndromes. It weighs 5 mg and measures 1.27 mm in diameter with a length of 3.5 mm. It is inserted into the inferior fornix. SODI Soluble ocular drug inserts. Small oval wafer. Sterile thin film of oval shape. Weighs 15-16 mg. Use – glaucoma. Lacriserts

22. Minidisc Countered disc with a convex front and a concave back surface. Diameter – 4 to 5 mm. Composition Silicone based prepolymer (4-methacryloxy)-butyl poly di methyl siloxane . (M2DX) M-Methyl a cryloxy butyl functionalities. D – Di methyl siloxane functionalities. Pilocarpine , chloramphenicol .

23. Type Advantages Disadvantages Erodible inserts Effective. Flexiblility in drug type & dissolution rate. Need only be introduced into eye & not removed. Patient discomfort . Requires patient insertion. Non-erodible inserts Controlled rate of release. Prolonged delivery. Flexibility for type of drug selected. Sustained release. Patient discomfort. Irritation to eye. Tissue fibrosis. Advantages And Disadvantages Of Ocular Inserts

24. 1. Implants Implants have been widely employed to extend the release of drugs in ocular fluids and tissues particularly in the posterior segment. Implants can be broadly classified into two categories based on their degradation properties: (1) Biodegradable (2) Nonbiodegradable Implants can be solids, semisolids or particulate-based delivery systems.

25. For chronic ocular diseases like cytomegalo virus (CMV) retinitis, implants are effective drug delivery system. Earlier non biodegradable polymers were used but they needed surgical procedures for insertion and removal. Presently biodegradable polymers such as Poly Lactic Acid (PLA) are safe and effective to deliver drugs in the vitreous cavity and show no toxic signs.

26. EVALUATION OF OCDDS . Thickness of film 2. Content uniformity 3. Uniformity of Weight 4. Percentage moisture absorption 5. Percentage moisture loss 6. In-vitro drug release 7. In-vivo drug release 8. Accelerated stability studies