occular ppt.pptx
- 2. • The novel approach of drug delivery in which the drug is instilled on the cul de sac cavity of the eye (space between eyelids and eyeballs) is known as Ocular Drug Delivery System.
- 3. • INTRODUCTION • Ocular administration of drug is primarily associated with the need to treat ophthalmic diseases. • Eye is the most easily accessible site for topical administration of a medication. • Ideal ophthalmic drug delivery must be able to sustain the drug release and to remain in the vicinity of front of the eye for prolong period of time.
- 4. The eye is a complex organ with unique anatomy and physiology. The structure of the eye can be divided into two main parts: the anterior segment and the posterior segment. The anterior segment of the eye occupies approximately one-third while the remaining portion is occupied by the posterior segment. Tissues such as the cornea, conjunctiva, aqueous humor, iris, ciliary body, and lens make up the anterior portion. Back of the eye or posterior segment of the eye include; sclera, choroid, retinal pigment epithelium, neural retina, optic nerve, and vitreous humor.
- 5. • The anterior and posterior segment of the eye is affected by various vision-threatening diseases. • glaucoma, allergic conjunctivitis, anterior uveitis, and cataract. • Age-related macular degeneration (AMD) and diabetic retinopathy
- 6. • Eye is composed of • Water – 98%, • Solid – 1.8%, • Protein – 0.67%, • Sugar – 0.65%, • NaCl – 0.66%, • other mineral element Sodium, Potassium and Ammonia – 0.79%.
- 8. Nasolachrymal drainage system Nasolachrymal drainage system consists of three parts; the secretory system, the distributive system and the excretory system. The secretory portion is composed of the lacrimal gland that secreted tears are spread over the ocular surface by the eyelids during blinking. The secretory system is stimulated by blinking and temperature change due to the tear evaporation and reflux secretors that have an efferent parasympathetic nerve supply and secrete in response to physical and emotional stimulation e.g. crying.
- 9. The distributive system consists of the eyelids and the tear meniscus around the lid edges of the open eye, which spread tears over the ocular surface by blinking, thus preventing dry areas from developing. The excretory part of the Nasolachrymal drainage system consists of the lachrymal puncta, the superior, inferior and common canaliculi; the lachrymal sac, and the nasochrymal duct. In humans, the two puncta are the openings of the lachrymal canaliculi and are situated on an elevated area known as the lachrymal papilla. It is thought that tears are largely absorbed by the mucous membrane that lines the ducts andthe lachrymal sac; only a small amount reaches the nasal passage
- 10. Tearfilm The exposed part of the eye is covered by a thin fluid layer, the so- called precorneal tear film. The film thickness is reported to be about 3–10 Am depending on the measurement method used. The resident volume amounts to about 10μl. The osmolality of the tear film equals 310–350 mOsm/kg in normal eyes and is adjusted by the monovalent and divalent inorganic ions such as Na+, K+, Cl-, HCO3-, and proteins. The mean pH value of normal tears is about 7.4.
- 11. • There are specialized dosage forms designed to be instilled onto the • external surface of the eye (topical), • administered inside (intraocular) or • adjacent (periocular) to the eye, or • used in conjunction with an ophthalmic device.
- 12. • The most commonly used employed dosage forms are the Solutions, Suspensions, and Ointments. • Topical administration is most popular and well accepted route of administration • The newest dosage forms are the • Gels, Gel forming Solutions, Ocular inserts, intravitreal injections, and implants.
- 13. • Mechanism of Ocular Drug Absorption • Drugs administered by instillation must penetrate the eye and do so primarily through the cornea followed by the non-corneal routes.These non-corneal routes involve drug diffusion across the conjunctiva and sclera and appear to be particularly important for drugs that are poorly absorbed across the cornea
- 14. • Corneal permeation • The permeation of drugs across the corneal membrane occurs from the precorneal space. Transcellular transport occurs i.e. transport between corneal epithelium and stroma. • The productive absorption of most ophthalmic drugs results from diffusional process across corneal membrane. • Maximum absorption thus takes place through cornea, which leads the drug into aqueous humor. • Outer epithelium has only access to small ionic and lipophilic molecules.
- 15. • Non-corneal permeation • Primary mechanism of drug permeation is diffusion across sclera & conjunctiva into intra ocular tissues. • Although like cornea, the conjunctiva is composed of an epithelial layer covering an underlying stroma, the conjunctival epithelium offers substantially less resistance than does the corneal epithelium. • This route is however, not productive as it restrains the entry of drug into aqueous humor. • This route is important for hydrophilic and large molecules, such as insulin and p-aminoclonidine, which have poor corneal permeability.
- 16. Factors Affecting Intraocular Bioavailability • Lacrimal fluids. • Naso-lacrimal drainage. • Interaction of drug with proteins of lacrimal fluids. • Dilution with tears. • Corneal barriers. • Active ion transport at the cornea.
- 17. • Ophthalmic dosage forms are sterile products essentially free from foreign particles, suitably compounded, and packaged for instillation into the eye. • Some of the dosage forms have been developed for Ocular drug delivery systems.
- 18. Ocular Drug Delivery Systems
- 19. Advantages of Ocular Drug Delivery System • 1. Increased accurate dosing. To overcome the side effects of pulsed dosing produced by conventional systems. 2. To provide sustained and controlled drug delivery. 3. To increase the ocular bioavailability of drug by increasing the corneal contact time. This can be achieved by effective adherence to corneal surface. 4. To provide targeting within the ocular globe so as to prevent the loss to other ocular tissues. 5. To circumvent the protective barriers like drainage, lacrimation and conjunctival absorption.
- 20. Disadvantages of Ocular Drug Delivery System • The residence time of the drug at the eye surface is less. • Poor bioavailability. • The instability of the dissolved drug. • The low concentration of preservatives reduces shelf life after opening the bottle.
- 21. Ideal Characteristics of Ocular Drug Delivery System • It should be sterile. • It should be isotonic to body fluids. • Buffer/pH adjustment. • Less drainage tendency. • Minimum protein binding.
- 22. Barriers to Ocular Drug Delivery System • When a dosage form is either administered topically or systemically, it faces multiple obstacles before it reaches its site of action. As a result, ocular bioavailability from topically administered drugs is usually only 1%-7% of the applied dose. These barriers can be broadly classified as anatomical barriers and physiological barriers.
- 23. Barriers of Ocular Drug Delivery System
- 24. Drug loss from the ocular surface After instillation, the flow of lacrimal fluid removes instilled compounds from the surface of eye. Even though the lacrimal turnover rate is only about 1 µl/min the excess volume of the instilled fluid is flown to the nasolacrimal duct rapidly in a couple of minutes. Another source of non-productive drug removal is its systemic absorption instead of ocular absorption. Systemic absorption may take place either directly from the conjunctival sac via local blood capillaries or after the solution flow to the nasal cavity.
- 25. • Lacrimal fluid-eye barriers Corneal epithelium limits drug absorption from the lacrimal fluid into the eye. The corneal epithelial cells form tight junctions that limit the paracellular drug permeation. • Therefore, lipophilic drugs have typically at least an order of magnitude higher permeability in the cornea than the hydrophilic drugs. In general, the conjunctiva is leakier epithelium than the cornea and its surface area is also nearly 20 times greater than that of the cornea
- 26. Blood-ocular barriers The eye is protected from the xenobiotics in the blood stream by blood-ocular barriers. These barriers have two parts: blood-aqueous barrier and blood-retina barrier. The anterior blood-eye barrier is composed of the endothelial cells in the uveam (The middle layer of the eye beneath the sclera. It consists of the iris, ciliary body, and choroid). This barrier prevents the access of plasma albumin into the aqueous humor, and also limits the access of hydrophilic drugs from plasma into the aqueous humor. The posterior barrier between blood stream and eye is comprised of retinal pigment epithelium (RPE) and the tight walls of retinal capillaries. Unlike retinal capillaries the vasculature of the choroid has extensive blood flow and leaky walls. Drugs easily gain access to the choroidal extravascular space, but thereafter distribution into the retina is limited by the RPE and retinal endothelia.
- 27. • 3. Blood Ocular Barrier: • This barrier normally keeps most drugs out of the eye, but inflammation breaks down this barrier allowing drugs and large molecules to penetrate the eye. • (a) Blood aqueous barrier: The ciliary epithelium and capillaries of the iris. • (b) Blood retinal barrier: Non-fenestrated capillaries of the retinal circulation and tight junctions between retinal epithelial cells preventing passage of large molecules from choriocapillaris into the retina.
- 28. • 2. Physiological Barriers: • The eye’s primary line of defense is its tear film. • The bioavailability of topically administered drugs is further reduced by precorneal factors such as; solution drainage, tear dilution, tear turnover, and increased lacrimation. • This in turn lowers the exact time for absorption leading to reduced bioavailability. • Prevention: So, the drugs administered as eye drops need to be isotonic and nonirritating to prevent significant precorneal loss.
- 29. Methods to Overcome Barriers to Ocular Drug Delivery • 1. Intravitreal Injections: Intravitreal injection (IVI) involves delivering the drug formulation directly into the vitreous humor through pars plana. • This method provides direct access to the vitreous and avoids both the cornea and also the scleral blood vessels. Formulations such as; solution, suspension, or a depot formulation can be administered through this route. Drug elimination occurs either through the retina or the anterior chamber through the aqueous humor following a first- order rate of decline.
- 30. This rate of elimination has a linear correlation with the molecular weight of the drug. Larger molecules tend to have longer half-lives as high as several weeks as compared to less than 3 days for low molecular weight compounds. IVI administration is associated with adverse effects such as; retinal detachment, cataract, hyperemia, and endophthalmitis. Sustained release drug delivery systems can help by lowering the frequency of administration and thus allow for better patient complianc
- 31. • 2. Subconjunctival Injections: • This injection delivers the drug beneath the conjunctival membrane that lines the inner surface of the eyelid. • It allows for circumvention of both cornea and conjunctiva allowing the drug direct access to the sclera. It is much less invasive with lesser side effects when compared to intravitreal injections. • The method is an excellent route for delivering hydrophilic drugs as it bypasses their rate-limiting barriers allowing more drugs to enter into the vitreous.
- 32. • 3. Retrobulbar and Peribulbar Route: Retrobulbar injection is given through eyelid and orbital fascia and it places the drug into retrobulbar space. This mode administers the drug to the back of the eyeball and is used to deliver drugs such as; antibiotics and corticosteroids. This route is especially applicable for the delivery of anesthetic agents as it causes minor or no change in IOP though in certain orbital diseases the reverse is also possible. Yet, it is a very delicate procedure as it may damage the optic nerve and thus requires proper expertise and equipment.
- 33. • It is also a viable route for the delivery of anesthesia, especially in cases of cataract surgery. It is a safer route compared to the retrobulbar route with a reduced risk of injury. Though it is a safer method, unlike retrobulbar injection multiple cases of elevated intraocular pressure after peribulbar injections have been reported.
- 34. • 4. Sub-Tenon Injections: Sub-tenon injections are administered into a cavity between the tenon’s capsule and sclera using a blunt cannula. Pre-operative deep sedation is also not a requirement for this procedure. The sub-tenon route appears to be a better and safer route for delivering anesthesia relative to retrobulbar and peribulbar administration since it does not require sharp needles. Steroids injected through this route have also been shown to be effective in the treatment of uveitis, cystoid macular edema, complicating uveitis, and non-necrotizing scleritis.
- 35. • 5. Intracameral Injections: Intracameral route is similar to intravitreal injections, but this injection delivers the drug to the anterior chamber. Drugs administered through this route are limited to an anterior chamber with very limited access to the posterior segment. It is generally employed for anterior segment procedures such as cataract surgery. Clinical studies have reported that intracamerally delivered dexamethasone is effective in reducing postoperative inflammation in glaucomatous and non-glaucomatous patients. It is an efficient and often more cost-effective method of delivering antibiotics relative to topical antibiotics and antifungal agents.
- 36. Formulations for Ocular Drug Delivery System • . Conventional Delivery Systems • Eye drops • Ointments and Gels • Ocuserts and Lacriserts • 2. Vesicular Systems • Liposomes • Niosomes and Discomes (Giant Niosomes) • 3. Controlled Delivery Systems • Implants • Iontophoresis • Dentrimer • Microemulsion • Nanosuspension • Microneedle • Mucoadhesive Polymers
- 37. Inserts • Classification of Inserts • Non-Erodible Inserts: • (a) Ocusert • (b) Contact Lens • Erodible Inserts: • (a) Lacriserts • (b) SODI • (c) Mindisc
- 38. 1. Non-Erodible Inserts: (a)Ocuserts: It is a flat, flexible, elliptical device designed to be placed in the inferior cul-de-sac between (b) the sclera and eyelid which releases Pilocarpine continuously at a steady state for 7 days. It comprises 3 layers: 1.Outer Layer: Ethylene-vinyl acetate copolymer layer. 2.Inner Layer: Pilocarpine gelled with alginate main polymer. 3.A retaining ring of EVA impregnated with titanium dioxide. Example: Pilo 20 (20 mg/hr), Pilo 40 (40 mg/hr).
- 39. ocusert
- 40. b) Contact Lens: These are circular-shaped structures; dyes may be added during the polymerization. Drug incorporation depends on whether the structure is Hydrophilic or Hydrophobic.
- 41. 2. Erodible Inserts: (a) Lacriserts: It is a sterile rod-shaped device composed of HPC without preservatives. Its weight is 5 mg, its diameter is 12.5 mm and length is 3.5 mm. It is used in dry eye treatment, Keratitis Sica.
- 42. (b) SODI (Soluble Ocular Drug Insert): Inserted in Inferior Fornix. It is a small water-soluble wafer-like insert, composed of acrylamide vinyl Pyrrolidone, Ethyl acrylate. It weighs 15-16 mg. It softens in 10-15 sec., turns in viscous liquids in 10-15 minutes, and after 30-60 minutes becomes the polymeric solution. It is used in the treatment of Glaucoma and Trachoma.
- 43. • (c) Minidisc: It is made up of a counter disc with a convex front and concave back surface in contact with the eyeball. It measures 4-5 mm in diameter. It is composed of silicon-based prepolymer. E.g. Pilocarpine, Chloramphenicol.