IMPROVEMENTS IN OPTHALMIC DRUG DELIVERY SYSTEM

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<ol><li> 1. IJPRD, 2014; Vol 6(02): April-2014 (100 110) International Standard Serial Number 0974 9446 Available online on www.ijprd.com 100 -------------------------------------------------------------------------------------------------------------------------------------------------- IMPROVEMENTS IN OPTHALMIC DRUG DELIVERY SYSTEM: A REVIEW P. R. Patil*, K. J. Shivsharan, V.K.Salve and S. S. Shaikh 1 Department of Pharmaceutics, Government College of Pharmacy, Opposite Govt. Polytechnic, Osmanpura, Aurangabad (431 005), Maharashtra, India. ABSTRACT This article is a discussion to the question, what are the different methods of preparing conventional ocular drug delivery system, its major setbacks and steps to overcome those setbacks?The answer to this kind of question takes the route of lengthy research processes and gives the outcomes in the form of advancement of techniques in ophthalmic drug delivery system. In situ-gel, Ocusert, Osmotic minipumps, Implants, Ocufit, NODS (new ophthalmic delivery system) and gene delivery are some of the examples of recent advancements in the field of ocular drug delivery system. Now a days above mentioned formulations are playing a significant role in the treatment of anterior and posterior segment of eye diseases .This review also helps to select the drugs and polymer combinations while formulating inserts. Key words Eye, Ocular drug delivery, Conventional formulations, Ocusert, NODS New ophthalmic delivery system), Gene delivery etc. INTRODUCTION Anatomy, physiology and biochemistry of the eye renders this organ exquisitely impervious to foreign substances.In the treatment of eye disorders topical route is widely accepted. But the bioavailability of drugs through this route is very poor. The main cause behind this is protective mechanism of eye such as blinking, baseline and reflex lacrimation, and drainage that removes foreign substance from eye including drugs. Day by day formulation developers are doing many adjustments in formulation to overcome the problems related to bioavailability. Some of the good examples of that would be in situ gelling, increase in viscosity and development of novel formulations like Ocusert, Lacrisert, Neosomes etc. Formulation approaches: Qualities of a Modified-Release Ophthalmic Drug Delivery System: A well-designed modified release ophthalmic drug delivery system must [1] 1) Deliver the active ingredient to the right place, i.e., high conjunctival levels are useless when targeting the ciliary body. Correspondence Author P. R. Patil Government College of Pharmacy, Opposite Govt. Polytechnic, Osmanpura, Aurangabad (431 005), Maharashtra, India. Email: prpatilgcop@gmail.com </li><li> 2. International Journal of Pharmaceutical Research &amp; Development ISSN: 0974 9446 Available online on www.ijprd.com 101 2) Improve the ratio of local activity versus systemic effects. 3) Reduce the number of installations per day, once-a-day being considered the optimal goal, although some can consider twice daily is a better insurance against a forgotten administration. 4) Be easy to self-administer. 5) Not induce a foreign-body sensation, long lasting blurring, or a very bad aftertaste. 6) Not rely on exotic ingredients like new chemical entities or difficult-to-source. 7) Excipients (unless this is a key element) preferably, excipients should have a drug master file and history of safe use for humans. 8) Be sterilizable at industrial scale by a recognized process. 9) Be compatible with an efficient antimicrobial preservative, or packaging in unit doses must be a viable alternative. 10) Preferably be stored without specific conditions. 11) Be covered by a patent, since manufacturers can legitimately expect a return on R&amp;D investment. CLASSIFICATION OF OPTHALMIC DRUG DELIVERY SYSTEM [2] Classifications of Ocular Drug Delivery Systems Based Upon Physical Properties of Formulation[3] Solids Semi-solids Liquids Miscellaneous 1) Ocular inserts 2) Contact lenses 3) Corneal shield 4) Artificial tear insert 5) Filter paper strips 1) Ointments 2) Gels 1) Solutions 2) Suspensions 3) Sol to gel systems 4) Sprays 1) Ocular iontophoresis 2) Vesicular systems 3) Mucoadhesive dosage forms 4) Particulates 5) Ocular penetration Solids The concept of using solids for the eye is based on providing sustained release characteristics. Ocular inserts Ocular inserts are solid dosage form and can overcome the disadvantage reported with traditional ophthalmic systems like aqueous solutions, suspensions and ointments. The typical pulse entry type drug release behaviour observed with ocular aqueous solutions (eye drops), suspensions and ointments is replaced by more controlled, sustained and continuous drug delivery using a controlled release ocular drug delivery </li><li> 3. International Journal of Pharmaceutical Research &amp; Development ISSN: 0974 9446 Available online on www.ijprd.com 102 system. The ocular inserts maintain an effective drug concentration in the target tissues and yet minimize the number of applications consonant with the function of controlled release systems. Limited popularity inserts has been attributed to psychological factors, such as reluctance of patients to abandon the traditional liquid and semisolid medications, and to occasional therapeutic failures (e.g. unnoticed expulsion from the eye, membrane ruptures etc.). A number of ocular inserts were prepared utilizing different techniques to make soluble, erodible, nonerodible, and hydrogel inserts. [4] Contact lenses Contact lenses can absorb water soluble drugs when soaked in drug solutions. These drug saturated contact lenses are placed in the eye for releasing the drug for long period of time. The hydrophilic contact lenses can be used to prolong the ocular residence time of the drugs. In humans, the Bionite lens which was made from hydrophilic polymer (2-hydroxy ethylmethacrylate) has been shown to produce a greater penetration of fluorescein. [5] Corneal Shield A non cross-linked homogenized, porcine scleral collagen slice is developed by a company (Biocor Bausch and Lomb pharmaceuticals). Topically applied antibiotics have been used in Conjunction with the shield to promote healing of corneal ulcers. Collagen shields are fabricated with foetal calf skin tissue and originally developed as a corneal bandage. These devices, once softened by the tear fluid, form a thin pliable film that confirms exactly to the corneal surface, and undergoes dissolution up to 10, 24 or 72 hours. Collagen film proved as a promising carrier for ophthalmic drug delivery system because of its biological inertness, structural stability and good biocompatibility. Gussler et al investigated the delivery of Trifluoro thymidine (TFT) in collagen shields and in topical drops in the cornea of normal rabbits and corneas with experimental epithelial tissue. It was found that highest drug concentrations were found in the eyes treated with shields as compared to eye drops. Artificial Tear Inserts A rod shaped pellet of Hydroxypropyl cellulose without preservative is commercially available (Lacrisert). This device is designed as a sustained release artificial tear for the treatment of dry eye disorders. It was developed by Merck, Sharp and Dohme in 1981. [6] Filter Paper Strips Sodium fluorescein and rose Bengal dyes are commercially available as drug impregnated filter paper strips. These dyes are used diagnostically to disclose corneal injuries and infections such as herpes simplex, and dry eye disorders. Semi-solids A wide variety of semisolids vehicles are used for topical ocular delivery which falls into two General categories: simple and compound bases. Simple bases refer to a single continuous phase. These include white petrolatum, lanolin and viscous gels prepared from polymers such as PVA, Carbapol etc. Compound bases are usually of a biphasic type forming either water in oil or oil in Water emulsions. A drug in either a simple or compound base provide an increase in the duration of action due to reduction in dilution by tears, reduction in drainage by way of a sustained release effect, and prolonged corneal contact time. The most commonly used semisolid preparation is ointment consisting of dispersion of a solid drug in an appropriate vehicle base. Semi-solids dosage forms are applied once or twice daily and provide sustained effects. The primary purpose of the ophthalmic ointment vehicle is to prolong drug contact time with the external ocular surface. But they present a disadvantage of causing blurring of vision. Ophthalmic gels are similar in viscosity and clinical usage to ophthalmic ointments. Pilopine HS is one of the ophthalmic preparations available in gel form and is intended to provide sustained action of pilocarpine over a period of 24 hours. Semi-solids vehicles were found to prolong the </li><li> 4. International Journal of Pharmaceutical Research &amp; Development ISSN: 0974 9446 Available online on www.ijprd.com 103 ocular contact time of many drugs, which ultimately leads to an enhanced bioavailability [7] . Liquids Liquids are the most popular and desirable state of dosage forms for the eye. This is because the drug absorption is fastest from this state. The slow release of the drug from the suspended solids provides a sustained effect for a short duration of time. Solutions and Suspensions Solutions are the pharmaceutical forms most widely used to administer drugs that must be active on the eye surface or in the eye after passage through the cornea or the conjunctiva. The drug in the solution is in the dissolved state. This form also have disadvantages; the very short time the solution stays at the eye surface, its poor bioavailability (a major portion i.e. 75% is lost via nasolacrimal drainage), the instability of the dissolved drug and the necessity of using preservatives. The retention of a solution in the eye is influenced by viscosity, hydrogen ion concentration, the osmolality and the instilled volume. Extensive work has been done to prolong ocular retention of drugs in the solution state by enhancing the viscosity or altering the pH of the solution. [8] Sol to gel Systems The new concept of producing a gel in situ (eg. in the cul-de-sac of the eye) was suggested for the first time in the early 1980s. It is widely accepted that increasing the viscosity of a drug formulation in the precorneal region will lead to an increased bioavailability, due to slower drainage from the cornea. Several concepts for the in situ gelling systems have been investigated. These systems can be triggered by pH change, temperature change or by ion activation. An anionic polymeric dispersion shows a low viscosity up to pH 5. 0 and will coacervate in contact with tear fluid due to presence of a carbonic buffer system which regulates the pH of tears. In situ gelling by a temperature change is produced when the temperature of polymeric dispersion is raised from 25 to 37C. Ion activation of polymeric dispersion occurred due to the presence of cations in the tear fluid. Wei et al. developed a thermosetting gel with a suitable phase transition temperature by combining Pluronic analogs and examined the influence of incorporating mucoadhesive polysaccharide, sodium hyaluronate (HA-Na), on the ocular retention of the gel by dynamic rheological method and single photon emission computing tomography (SPECT) technique. Sprays Although not commonly used, some practitioners use mydriatics or cycloplegics alone or in combination in the form of eye spray. These sprays are used in the eye for dilating the pupil or for cycloplegic examination. Recent developments in ophthalmic drug delivery Ocular drug delivery devices Ocular drug delivery devices include matrix type drug delivery systems, capsule type drug delivery systems and implantable drug delivery pumps[9] . Matrix-type Drug Delivery Systems:- Hydrophilic Soft Contact Lenses Hard contact lenses, soft contact lenses and intraocular lenses are popular for correction of refractive errors of the eye and several kinds of polymer have been used for the preparation theses lenses. Because they are easy to fit hydrophilic soft contact lenses are more popular. They are made up of hydrogels that absorb certain amounts of aqueous solutions, because of this property they have also been found useful for drug delivery to anterior segment of the eye. [10] The hydrophilic contact lenses, Bionite was developed by Griffin laboratory, and Soflens, was developed by Bausch &amp; Lomb as devices for maintaining high concentration in anterior chamber of the eye. They used fluorescein as a model drug. They have achieved four times greater concentration than those from frequent administration of drops in the </li><li> 5. International Journal of Pharmaceutical Research &amp; Development ISSN: 0974 9446 Available online on www.ijprd.com 104 case of Bionite lens pre-soaked with the drug as well as a pre-soaked Soflens also. They have also performed human studies and found that a Bionite could maintain the fluorescein concentration in the ocular tissues for 24 h despite the known rapid clearance of fluorescein from the eye. Kaufman et al. studied the usefulness of soft contact lenses for antiviral idoxuridine (IDU), polymyxin B and pilocarpine as drug delivery devises to the eye. Hull et al., 1992 studied the ocular penetration of predinsolone sodium phosphate in rabbit eye and the effect of a hydrophilic contact lens on the penetration. The contact lenses made from PHP (hefilcon-A) copolymer (80% 2-hydroxyethylmethacrylate and 20% N-vinyl-2-pyrrolidone), were of 16 mm in diameter and 0.3 mm thickness, and their hydration was 40% to 45%. The lenses were pre- soaked in predinsolone sodium phosphate for 2 min., they were able to maintain the aqueous and corneal levels two to three times higher, for 4 hr, than the levels obtained after topical administration of plane predinsolone solution. After a 2 hr or 4 hr pre-soaking time, they measured the amount drug released into fresh saline baths for up to 3 hr Ciprofloxacin hydrochloride, predinsolone sodium phosphate, and cromolyn sodium were found to be released from the disposable contacts at a rate that provided higher concentrations of drug for a longer period of time than would be expected with drops. Depending on the lens used these drugs were released continuously for a period of up to 3 h. Disposable lenses soaked in pilocarpine hydrochloride or idoxuridine released drug for 30 min or less. They found that disposable contact lenses could provide an acceptable means of drug delivery for some situations and overcome drawbacks associated with the use of nondisposable hydrogel lenses. Soluble Ocular Inserts Soluble ocular inserts, such as the poly (vinyl alcohol) insert (PVAI), the soluble ophthalmic drug insert (SODI) and polypeptide devises are matrix type polymeric devises used for drug delivery to eye. Poly (vinyl alcohol) inserts are characteristically thin, elastic and oval shaped plates and impregnated...</li></ol>

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