Ocular Drug Delivery

- Rapid pre-corneal elimination - Solution drainage by gravity - Frequent instillation is necessary - Conjunctival absorption What are some limitations of conventional drug delivery? - Sustained and/or controlled drug release - Site-specific targeting What are some advantages of drug de- - Protect the drug from chemical or enzylivery? matic hydrolysis - Increasing contact time and this improving bioavailability - Better patient compliance. Pre-corneal Constraint: solution drainage, lacrimation, tear dilation, tear turnover, conjunctival absorption What are some barriers in ocular absorpCorneal Constraints: cornea as rate limtion? iting barrier, anatomy of cornea (1. Outer-Epithelium (lipophilic), 2. Middle-Stroma (hydrophilic), 3. Inner-Endothelium (lipophilic) Corneal Absorption - depend on physiochemical properties of drug - only access to small ionic and lipophilic molecules - outer epithelium: rate limiting barrier - trans cellular transport: transport between corneal epithelium and stroma eg Pilocarpine Non-Corneal Absorption - penetration across sclera and conjunctiva into intra ocular tissue - non-productive: because penetrated drug is absorbed by general circulation - minor pathway - important for drug with low corneal permeability 1/5 eg Insulin SLIDE 8 - mucoadhesives contain the dosage form which remains adhered to cornea until the polymer is degraded or mucus replaces itself. Types include: What are mucoadhesives and the differ- 1) Naturally occurring mucoadhesives : ent types: Lectins, Fibronectins 2) Synthetic Mucoadhesives- PVA, Carbopol, Carboxy Methyl Cellulose, Cross-linked polyacrylic acid eg Pilocarpine, Lidocaine, Benzocaine and Prednisolone acetate. MOA of Mucoadhesion - the polymer undergoes swwelling 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-soluble yet water-insoluble system are preferred Nanoparticulate drug delivery - Size 10-1000nm - Types: Nanospheres and nanocapsules - Drug is dispersed, encapsulated or adsorbed - Particulate systems in nanoparticulate drug delivery- 1) Topical system eg chloramphenicol (suspended) 2) local injectable system eg 5FU - Polymers used are biodegradable eg polyalkylacrylates 2/5 - Sustained drug release and prolonged therapeutic activity - Site-specific targeting - higher cellular permeability - protect the drug from chemical or enzyWhat are the advantages of nanoparti- matic hydrolysis cles? - efficient in crossing membrane barriersblood retinal barrier - act as an inert carrier for ophthalmic drugs SLIDE 14 What are ocular inserts? Sterile preparation with a thin, multilayered, drug-impregnated, solid or semisolid consistency devices places into cul-de-sac or conjunctival sac. Advantages of Ocular Inserts - 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) What are the desired criteria for ocular - Applicability to variety of drugs inserts? - non-interference with vision and oxygen permeability - sterility - ease of manufacture What are the different examples of ocular inserts? 3/5 - insoluble inserts - bio-erodible inserts - soluble inserts Examples SLIDE 17 1) Diffusional inserts: - Central reservoir of drug enclosed in semi-permeable or microporous membrane for diffusion of drug - diffusion is controlled by lacrimal fluid penetrating through it Insoluble Inserts: 1) Diffusional Inserts - Release follows: zero order kinetics eg Ocusert 20-40µg/hour for 7 days Annular ring: impregnated with TiO2: for visibility 2) Osmotic Inserts - a central part surrounded by a peripheral part - central part-single reservoir or two distinct compartments. - peripheral part: an insoluble semi permeable polymer - solubilised deposits generate a hydrostatic presssure. - drug is then released through these apertures. 3) Contact Lens: - pre-soaked hydrophilic lens - drug release: within 1st 30 mins - alternate approach: incorporate drug either as solution or suspension eg Pilocarpine - release rate is up to 180 hours Soluble Inserts 1) SODI: Soluble Ocular Drug Insertsmall water soluble made of soluble synthetic polymers. - Composition: Acryl amide, Vinyl Pyrolidone, Ethylacrylate - Weight 15-16 mg. In 10-15 sec Softens; 4/5 In 10-15 min. turns in Viscous Liquids; After 30-60min. Becomes Polymeric Solution Advantages Single SODI application: replaces4-12 eye drops instillation, or 3-6 application of ointments Once a day treatment of Glaucoma Biodegradable Inserts: 1) Lacrisert - sterile, rod shaped device - composition: HPC - weight: 5mg - Dimension:Diameter 12.5mm, Length 3.5mm - Use: dry eye treatment 2) Minidisc - it is made up of counter disc with convex front and concave back surface in contact with eye ball - 4-5mm in diameter - composition: silicon based polymer - drug release up to 170 hours the sustained and controlled release technologies are being proposed and the possible benefits of using liposomes, nanoparticles and inserts will be at store in future. Future targeted drug delivery with modifications of conventional advanced and novel ocular drug deliveries has potential as future drug delivery for eye. Delivery of siRNA via ocular route. 5/5