Definition: They 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. Conventional ophthalmic dosage forms (solutions, suspensions, ointments, etc) after instillation into the eye, are rapidly drained away from the ocular cavity due to tear flow and lacrimal nasal drainage. The newest dosage forms for ophthalmic drug delivery are: liposomes, nanoparticles ,mucoadhesives,ocular inserts.
LIMITATIONS OF CONVENTIONAL DRUG DELIVERY Solution drainage by gravity Frequent instillation is necessary Conjuctival absorptionADVANTAGES OF AVANCED DUG DELIVERY Sustained and/or controlled drug release Site-specific targeting Protect the drug from chemical or enzymatic hydrolysis Increasing contact time and thus improving bioavailability Better patient compliance.
• Penetration across Sclera & Conjuctiva into Intra Ocular tissues • Non-Productive: because penetrated drug isNon-Corneal absorbed by general circulation Absorption • Outer Epithelium: rate limiting barrier, with pore size 60å,Only access to small ionic & lipophillic molecules Corneal • Trans cellular transport: transport between corneal epithelium & stroma.Absorption
Mucoadhesives contain the dosage form which remains adhered to cornea until the polymer is degraded or mucus replaces itself. Types-1. Naturally Occurring Mucoadhesives- Lectins, Fibronectins2. Synthetic Mucoadhesives-PVA ,Carbopol, carboxymethylcellulose,cross-linked polyacrylic acidDrugs incorporated in to this are pilocarpine, lidocaine, benzocaine and prednisolone acetate.
• The polymer undergoes swelling in water,• Entanglement of the polymer chains with mucin on the epithelial surface.• The un-ionized carboxylic acid residues on the polymer form hydrogen bonds with the mucin.• The water- swellable yet water- insoluble systems are preferred
Sterile preparations, with a thin, multilayered, drug-impregnated, solid or semisolid consistency devices placed into cul-de-sac or conjunctival sac.Advantages Increasing contact time and thus improving bioavailability. Providing a prolong drug release and thus a better efficacy. Reduction of systemic side effects and thus reduced adverse effects. Reduction of the number of administrations and thus better patient compliance.
* Ease of handling and insertion* Lack of expulsion during wear* Reproducibility of release kinetics (Zero-order drug delivery)* Applicability to variety of drugs* Non-interference with vision and oxygen permeability.* Sterility.* Ease of manufacture
1. Ocusert: is a multilayered structure consisting of a drug containing core surrounded on each side by a layer of copolymer membranes through which the drug diffuses at a constant rate. The rate of drug diffusion is controlled by:- The polymer composition- The membrane thickness- The solubility of the druge.g. The Ocusert® Pilo-20 and Pilo-40 Ocular system- 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 7days.- consists of (a) a drug reservoir, pilocarpine (free base), and a carrier material, alginic acid: (b) a rate controller ethylene vinyl acetate (EVA) copolymer membrane.
2. Contact lens: Presoaked Hydrophilic lens. Drug Release : within 1st 30 Min. Alternate approach : incorporate drug either as soln or suspension .e.g. Pilocarpine. Release rate is up to : 180 hr.
1. SODI (soluble ocular drug insert):• Small water soluble made of soluble synthetic polymers.• Composition : Acryl amide, Vinyl Pyrolidone, Ethylacrylate.• Weight 15-16 mg. In 10-15 sec Softens; In 10-15 min. turns in Viscous Liquids; After 30-60min. Becomes Polymeric Solution. ADVANTAGES:•Single SODI application : replaces 4-12 eye drops Instillation, or 3-6 application of Ointments.•Once a day treatment of Glaucoma.
2.Lacrisert:• Sterile, Rod Shaped device.• Composition: HPC.• Weight:5mg,• Dimension:Diameter:12.5mm, Length:3.5mm• Use:-Dry eye treatment.3.Minidisc: It is made up of counter disc with Convex front & Concave back surface in contact with eye ball. 4-5mm in diameter. Composition : Silicon based polymer. Drug release upto170 hr.
Vesicle composed of phospholipid bilayer enclosing aqueous compartment in alternate fashion. Biodegradable, Non-toxic in nature. Types :1.MLV 2.ULV-SUV( upto 100 nm) 3. LUV(more than 100 nm) Polar drugs are incorporated in aqueous compartment while lipophilic drug are intercalated into the liposome membrane. Phospholipids used- Phophotidylcholine, Phosphotidic acid, Phosphotidyleserine,Cardiolipine
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 OF LIPOSOMES They need many modification for drug delivery to special organs. Cost .
For water soluble drugs Size is about 10-1000 nm Drug is dispersed, encapsulated or absorbed Produced by emulsion polymerization Polymerization is carried out by chemical initiation, or by irradiation with gamma rays, uv or visible light. Polymer used are biodegradable. E.g: Nanoparticles of pilocarpine have shown an enhanced miotic response by about 22-23%.
Advantages of Nanoparticles Sustained drug release and prolonged therapeutic activity Site-specific targeting Higher cellular permeability Protect the drug from chemical or enzymatic hydrolysis Efficient in crossing membrane barriers -blood retinal barrier Act as an inert carrier.