In vitro release of cupric ion from intrauterine devices: influence of frame, shape, copper surface area and indomethacin

Abstract

The release of cupric ion from copper intrauterine device (Cu-IUD) in human uterus is essential for contraception. However, excessive cupric ion will cause cytotoxic effect. In this paper, we investigated the influence of device characteristics (frame, copper surface area, shape, copper type and indomethacin) on copper release for the efficacy and adverse effects vary with IUD types which may correlate to their different release behaviors. Nine types of Cu-IUDs were selected and incubated in simulated uterine fluid. They were paired for comparison based on the device properties and the release of cupric ion was determined by flame atomic absorption spectrometer for about 160 days. The result showed that there was a burst release during the first month and the release rate tends to slow down and become steady afterwards. In addition, the copper release was mainly influenced by frame, indomethacin and copper type (copper wire and copper sleeve) while the shape variation had little effect on copper release throughout the experiment. Moreover, the influence of copper surface area was only noticeable during the first month. These findings were seldom reported before and may provide some useful information for the design of Cu-IUDs.

Clinical characteristic and intraoperative findings of uterine perforation patients in using of intrauterine devices (IUDs)

“…In the early years, most IUDs were steel rings (designated as O-shaped in this study) due to its low cost, and the devices were provided free of charge in some hospitals [ 1 , 22 ]. Later, the copper-releasing IUDs replaced the steel rings as many problems were encountered by using the rings [ 29 ].Nowadays, copper-releasing IUDs have become the prevailing devices in clinical application in China [ 22 , 24 ]. Recently, the levonorgestrel intrauterine system (LNG-IUS) along with other optimized IUDs were also provided to Chinese women [ 25 ].…”

“…In the 1990s, the use switched to T-shaped copper IUDs, although a large population of women was still using the steel rings [ 21 ]. Today, there are dozens of different types of IUDs available on the market that clearly mirror their clinical application [ 22 – 24 ]. Most of the IUDs used in China are manufactured in China, and the majority is the copper-releasing IUDs, including all types of T-shaped and V-shaped copper-releasing IUDs.…”

Simulated Genital Tract Fluids and Their Applicability in Drug Release/Dissolution Testing of Vaginal Dosage Forms

“…A number of additional authors reported the use of SUFs in studying copper, zinc, or indometacin release from IUDs (40)(41)(42)(43)(44)(45)(46)(47). However, in all of these studies, the media designed by Zhang et al (35) or the slightly modified version reported by Mora et al (39) were applied.…”

Intrauterine Contraception

“…The Chinese have produced five different copper IUDs containing indomethacin with the goal of reducing menstrualrelated complaints that occur with currently available copper IUDs. [45][46][47] The indomethacin does not interfere with copper ion release and the copper does not interfere with indomethacin action. 47 One such device, the Medicated Gamma IUD, is a gammashaped stainless steel wire frame, with 250 mm 2 of spiraled copper wire on a 26 mm  26 mm frame.…”

“…Silicon rubber containing indomethacin 18 mg lines the inside of the stainless steel wire tube that makes up the IUD frame. 46 Unfortunately limited data are available in the English literature to understand all of the various frames, efficacy, and side effects of these medicated IUDs; however, one review article includes a nonreferenced table of a few Chinese copper IUDs, with pregnancy rates ranging from 0.46 to 2.73%, and effective duration between 5 and 10 years. 46…”