Pilocarpine implant

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. 

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. 

An alternative system, manufactured as a wafer-like insoluble implant, has been developed (Ocusert). The system is preprogrammed to release pilocarpine at a constant rate of 20 or 40 / g/hr for a week to treat chronic glaucoma however, release from inserts may be incomplete and approximately 20% of all patients treated with the Ocusert lose the device without being aware of the loss. The device also presents problems including foreign-body sensation, expulsion from the eye, and difficulty in handling and insertion. An alternative to the advanced non-erodible systems is an erodible insert for placement in the cul-de-sac. 

An erodible implant system based on PVA has also been investigated. The bioavailability of pilocarpine was shown to be increased sixteen-fold using this system. The system showed considerable promise for prolonged drug delivery since vision is minimally affected by the presence of an insert positioned on the sclera. When the device is placed in the lower fornix, the contact area for the released drug is the sclera and little material is in contact with the cornea. 

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). 

HA and hylans have been developed as topical, injectable, and implantable vehicles for the controlled and localized delivery of biologically active molecules (Larsen and Balazs, 1991). The most commonly studied HA delivery system is for the delivery of pilocarpine agent used in the management of tlie elet ated intraocular pressure associated wth glaucoma. Topical HA solutions (0.1-0.2%) have been shot Ti to be effective therapy for diy eye syndrome. 

Hydrogels able to release drugs or biomolecules in response to variations in electric field. Thus, Y. Osada and co-workers studied the electro-activated release of pilocarpin from microparticles of sodium salt of poy(acrylic acid) gel, Na-PAA [141]. It was found that insulin diffuses out of a gel made of weakly crosslinked polyelectrolyte gels when electric current is turned on, but the flow ceases immediately when it is turned off. This kind of gel could be the basis on an implantable insulin pump with no moving parts [142 ]. 

There are many attempts to insert or implant a gel that contains a drug. A DDS that consists of a sandwich of pilocarpine (for iris contraction) between ethylene-vinyl acetate copolymers, is an example of a DDS used for the eyes. 

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