Progestasert device

The use of rate-limiting membranes to control the movement of dmgs from a reservoir has been referred to above. Implants of silicone rubber or other appropriate polymeric material in which dmg is embedded can be designed by choice of polymer, membrane thickness and porosity, to release dmg at preselected rates. The Progestasert device (Fig. 8.34c) is designed to be implanted into the uterine... 

Figure 8.34 Examples of drug-delivery systems employing polymeric membranes, (o) Ocusert system for the eye with two rote-controlling membranes, (b) Tronsiderm system for transdermal medication with one rote-controlling layer, (c) The Progestasert device for intrauterine insertion in which the body of the device serves as the rote-controlling barrier, (d) The oral Oros device in which the membrane is o semipermeable membrane which forbids drug transport, allowing water ingress only.

As of 1994, there were approximately 47 progestin-containing contraceptive dmg formulations sold in the United States for use as oral contraceptives (Table 3). In addition, there are three nonoral contraceptive formulations containing progestins ie, one injectable (Depo-Provera), one as an intrauterine device (lUD) (Progestasert), and one implantable (Norplant). Of the oral formulations, all but two also contain an estrogen component, ethynylestradiol. 

Alza Corp. has also developed an iatrauteriae device, Progestasert, designed to release progesterone [57-83-0] by diffusion through a rate-controlling membrane for up to one year. The dmg reservoir is built into a T-shaped device that is inserted intravaginaHy (15). 

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. 

Fig. 16 Schematic diagram of the Progestasert intrauterine device for the release of progesterone.

The hormone-releasing devices have a closer resemblance to standard methods of sustained release because they involve the release of a steroid compound by diffusion [198,199]. The Progestasert, a reservoir system, is shown in Fig. 16. Progesterone, the active ingredient, is dispersed in the inner reservoir, surrounded by an ethylene/vinyl acetate copolymer membrane. The release of progesterone from this system is maintained almost constant for 1 year. The effects of release are local, with none of the systematic side effects observed with orally administered contraceptives [200-207]. 

Figure 12.9 Progestasert intrauterine device (IUD) designed to deliver progesterone for contraception at 65 p,g/day for 1 year [19]...

EVA copolymers are also used in fabricating Progestasert and Ocusert which are an intrauterine and an ocular drug delivery device for pilocarpine and progesterone, respectively. These are discussed in Chapters... 

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... 

The Progestasert intrauterine device (lUD) is a contraceptive lUD marketed in the United States. It is a white, T-shaped unit constructed of ethylene-vinyl acetate copolymer containing titanium dioxide. It releases progesterone at a rate of 65 pg/day for 1 year, controlled by an outer coat of ethylene-vinyl acetate... 

An innovative progesterone-containing device (Progestasert) has been made available as a long-lasting intrauterine contraceptive. It contains 38 mg of the drug in a silicone oil solution, which on proper insertion releases 63 jig of progesterone per 24 hours for periods up to 1 year. The contraceptive effects of the device itself (an intrauterine device, IUD) is believed to be enhanced by the hormone s local effect on the endometrium. 

Progesterone undergoes rapid first-pass metabolism, but high-doses (e.g., 100—200 mg) of micronized progesterone (prometrium) are orally effective. Progesterone also is available in oil solution for injection, as a vaginal gel (CRINONE, PROCHIEVE), and as a slow-release intrauterine device (PROGESTASERT)for contraception. 

Progesterone/poly[ethylene-co-(vinyl acetate)] Progestasert , Alza Corp. Contraceptive intra-uterine device... 

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). 

Note. Progestasert, Alza an intrauterine contraceptive device consists of 38mg of progesterone in silicone oil. In this instance, the drug is believed to increase the contraceptive effectiveness of the said device by a local effect on the endometrium followed by effects upon the motility of sperm, capacitation and metabolism.]... 

The most well known commercial reservoir controlled release systems deliver hormones for contraception from hydrophobic polymers. The Norplant subcutaneous device controls the release of levonorgestrel with silicone rubber, and the Progestasert intrauterine device (lUD) releases progesterone from reservoir devices of ethylene vinyl acetate. In the field of insecticides, reservoir dispensers called BioLure were developed to provide zero-order release ofinsect pheromones to disrupt mating (Smith et al, 1983). The dispenser consists of a slab configuration with a rate-controlling membrane, with constant release described by Eq. 1. 

A second example of a reservoir controlled drug delivery system is the Progestasert inlra-uterine device (lUD), a medicated implant that is used for contraceptive purposes. In the 1960s lUDs emerged... 

Medical Letter (1976) Progestasert - a new intrauterine contraceptive device. 18, 65. 

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