Pilocarpine release

A.Urtti, Pilocarpine release from matrices of alkyl half-esters of poly( vinyl methyl ether/maleic anhydride), Int. 

Various lecithin-based MEs were also characterized by Hasse and Keipert [131]. The formulations were tested in terms of their physicochemical parameters (pH, refractive index, osmolality, viscosity, and surface tension) and physiological compatibility (HET-CAM and Draize test). In addition, in vitro and in vivo evaluations were performed. The tested MEs showed favorable physicochemical parameters and no ocular irritation as well as a prolonged pilocarpine release in vitro and in vivo. 

JW Sieg, JR Robinson. Vehicle effects on ocular drug bioavaiiability 111 shear-facilitated pilocarpine release from ointments. J Pharm Sci 68 724-728, 1979. 

In vitro release tests were carried out on 200 mg samples of polymer films, by determining pilocarpine release to a stirred aqueous medium (pH 6.98 phosphate buffer, 10.0 ml) at 30 °C. Solution samples (2.0 ml) were withdrawn at appropriate intervals, and were replaced with an equal amount of fresh buffer. Pilocarpine was analyzed spectrophotometrically by the ferric hydroxamate method described by Gibbs and Tuckerman... 

In P. microphyllus model, callus were also subjected to conditions and elicitors in an MS-liquid medium supplemented with 2,4-D as growth regulator [54]. Different nutrient concentration, pH value, type/concentration of elicitors (histidine, threonine and methyl jasmonic acid), and osmotic and salt stress (PEG and NaCl) were evaluated. Light incidence influence was also analyzed. Pilocarpine was released in the liquid medium from callus kept in the dark. Detection was carried out using HPLC-MS/MS techniques, and pilocarpine quantification was performed by HPLC. Elicitors induced highest accumulation of the alkaloid in a time/concentration relationship. Light incidence and methyl jasmonic acid inhibited pilocarpine release to the medium. 

Another method of pilocarpine release is the use of a thin laminate of hydrophile polymers inserted in the conjunctiva cul-de-sac. This pilocarpine Ocusert system releases pilocarpine at a constant pre-determined rate. The sustained-release system, providing such advantages as maximum duration of pressure control, less round-the-clock pressure variation, use of smaller drug concentrations with decrease of ocular and systemic side effects, also has some disadvantages one problem is the burst phenomenon, in which there is a large initial release of pilocarpine after insertion, resulting in severe miosis and ciliary body spasm. Up to the present several cases of loss of device and 8 -formation, comeal erosion, subconjunctival bleeding and displacement to the pupil have been reported. 

Fig. 2. Ocusert ocular therapeutic system. The Ocusert system releases pilocarpine at a controUed rate to treat glaucoma. In this schematic representation, the three disks and the ring are shown two-dimension ally. The patient inserts the Ocusert system under the eyeUd, where it releases pilocarpine for seven...

Fig. 3. Release rate of pilocarpine from Ocusert Pilo-20. Data points shown with standard deviation error bars (94).

The semi-interpenetrating polymeric networks obtained by the radical-induced polymerization of N-isopropylacrylamide in the presence of chitosan using tetraethyleneglycoldiacrylate as the cross-linker were used as controlled release vehicles for pilocarpine hydrochloride [294]. 

Drug delivery problems associated with pilocarpine, most notably low ocular bioavailability and short duration of action, continue to be significant (44). In an effort to prolong delivery and to avoid undesirable effects, an investigation was carried out on the incorporation and in vitro release of pilocarpine from a soluble film... 

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... 

Fig. 14 Schematic diagram of the Ocusert intraocular device for release of pilocarpine.

Ocular Therapeutic System Releases 20 or 40 meg pilocarpine/hour for 1 week (Rx)... 

Ophthalmic sustained-release inserts (Ocusert Pilo-20, Ocusert Pilo-40) release 20 and 40 meg pilocarpine per hour for 1 week, respectively... 

Pilocarpine, carbachol, physostigmine, echothiophate, demecarium Ciliary muscle contraction, opening of trabecular meshwork increased outflow Topical drops or gel plastic film slow-release insert... 

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. 

Loucas, S. P. and H. M. Haddad. 1972. Solid-state ophthalmic dosage systems in effecting prolonged release of pilocarpine in the cul-de-sad. Pharm. Sci61 985-986. 

Vandamme, T.F., and L. Brobeck. 2005. Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release 20 102. 

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