Alza Ocusert

Nondegradable polymers are also useful as matrices for ocular implants. This application requires the polymer to be hydrophilic, to minimize local tissue irritation. Need for ocular implants stems from the challenges posed to conventional ocular medicines (i.e., eye drops) such as rapid dilution, tear washout, poor patient compliance, and limited bioavailability. Ocular implants from hydrophilic polymer matrices that provide localized sustained release may overcome the above limitations. The first polymeric sustained release product to reach the market was Ocusert , a pilocarpin sustained release ocular implant developed by Alza. Ocusert has the drug reservoir as a thin disc of pilocarpine-alginate complex sandwiched between two transparent discs of microporous membrane fabricated from ethylene-vinyl acetate copolymer. The microporous membranes permit the tear fluid to penetrate into the drug reservoir compartment to dissolve pilocarpine from the complex. Pilocarpine molecules are then released at a constant rate of 20 or 40 pg/hr for a four- to seven-day management of glaucoma. 

Diffusion-controlled membranes exist in two categories depot systems, in which the drug is totally encapsulated within a reservoir, and monolithic systems, where the drug is dispersed in a rate-controlling polymer matrix [25]. One commercially successful depot device is the Alza Ocusert for ocular delivery of pilocarpine in the treatment of glaucoma [25]. 

The Alza Ocusert device (Fig. 9.39) releases controlled amounts of pilocarpine over a period of 7 days and is designed for the treat-Structure VII Dipivoyl epinephrine (dipivefrine compare ment of glaucoma. It comprises a dmg reser-with Structure VI) voir in which pilocarpine is embedded in an... 

Figure 9.39 (a) Dimensions and structure of the Alza Ocusert device, (b) A release rate profile over one week. 

Ophthalmic dmg dehveiy systems (qv) have been developed to dehvei controlled dmg quantities for a prolonged time (up to seven days) to the eye, eg, pilocarpine [92-13-7J (17). Alza Corp. in conjunction with Ciba-Geigy Corp. originally marketed such a product known as Ocusert to treat glaucoma. 

Ethylene vinyl acetate has also found major applications in drug delivery. These copolymers used in drug release normally contain 30-50 wt% of vinyl acetate. They have been commercialized by the Alza Corporation for the delivery of pilocarpine over a one-week period (Ocusert) and the delivery of progesterone for over one year in the form of an intrauterine device (Progestasert). Ethylene vinyl acetate has also been evaluated for the release of macromolecules such as proteins. The release of proteins form these polymers is by a porous diffusion and the pore structure can be used to control the rate of release (3). Similar nonbiodegradable polymers such as the polyurethanes, polyethylenes, polytetrafluoroethylene and poly(methyl methacrylate) have also been used to deliver a variety of different pharmaceutical agents usually as implants or removal devices. 

The Ocusert Pilo-20 and Pilo-40 Ocular Therapeutic System is an elliptical membrane that is soft and flexible and 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 design of the dosage form is described by Alza in terms of an open-looped therapeutic system, having three major components (a) the drug, (b) a... 

The Ocusert (pilocarpine) Pilo-20/Pilo-40 Ocular Therapeutic System, Alza Corporation, Palo Alto, CA (1974). 

Ocular inserts (epinephrin prodrug) Alginic acid Ocusert Alza... 

Several commercial examples of such devices have been introduced. The ALZA Corporation markets a device called OCUSERT wiiich is placed in the cul de sac of the eye and releases pilocarpine to control glaucoma. Another ALZA product called PROGESTASERT is placed in the uterus and releases progesterone to effect birth control Each of these are macroscopic devices however, microenr psulation is... 

Pilocarpine/poly]ethylene-co-(vinyl acetate)] Ocusert , Alza Corp. Glaucoma therapy... 

EVAc has been used in the fabrication of a variety of devices for drug delivery. For example, EVAc was used by Alza in devices to deliver pilocarpine to the surface of the eye for glaucoma treatment (Ocusert). Currently, EVAc is used in the Progestasert intra-uterine device for the delivery of contraceptive hormones to the female reproductive tract and as a rate-controlling membrane in a number of transdermal devices. Since EVAc is one of the most biocompatible of the polymers that have been tested as implant materials [30], it has been widely studied as a matrix for controlled drug delivery (see [31, 32] for reviews). 

Ethylene vinyl acetate OCUSERT Alza Treat glaucoma... 

First controiied release product registered -Ocusert Alza (1974)... 

Thermoplastic. Some of these copolymers are flexible without adding a plasticizer. For certain applications, they are superior to silicone mbber. They are stable and can be readily sterilized. DDS Ocusert of Alza uses EVA. copolymer film and Progestasert uses EVA polymer film. These copolymers with low vinyl acetate contents have greater hardness and have excellent mechanical and physical properties (used for improving wax or as adhesives). Those with high vinyl acetate content have the properties of rubber. This rubber has excellent compatibility with other rubbers and has good rolling characteristics and processability. They can be crosslinked by peroxides. They lack resistance to low temperature and solvents. 

Figure 2. OCUSERT ocular therapeutic system in the lower cul-de-sac of the eye. (Copyright 1975 ALZA corp.)...

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