COPPER IUD

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COPPER BEARING INTRAUTERINE DEVICES:

Submitted to: Presented by: Dr. Hemanth K S Yadav , Supraja Madhavan Dept. of Pharmaceutics 1 st yr M.Pharm , J.S.S.C.P. Mysore – 15 Pharmaceutics. COPPER BEARING INTRAUTERINE DEVICES

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Zipper et al. reported that Copper attached to IUD showed markedly enhanced contraception Their 1 st study was with a 30 mm 2 copper wire after which they evaluated IUD with larger surface areas of copper wire It was found that area of 200 mm 2 showed maximum contraceptive efficacy but further increase showed no significant improvement

Antifertility Action of Copper:

Antifertility Action of Copper In sufficiently high concentrations copper is known to be cytotoxic Significantly enhance the spermatocidal and spermatodepressive action Also found to be blastocystoidal and death rate of blastocyst is proportional to surface area of copper If inserted after implantation does not interfere with gestation and no abnormal malformations No interference with fertilization

Antifertility Action of Copper - MOA:

Antifertility Action of Copper - MOA Cupric ion is a competitive inhibitor of steroid-receptor interaction by acting on the receptor sites via the dissociation and aggregation of receptor macromolecules Progesterone receptor>Estrogen receptor Cupric ion is the most potent inhibitor; Cu> Cd >Zn> Pb When the concentration of copper is 1.4 x 10 -6 M, the inhibitory activity becomes apparent

Antifertility Action of Copper:

Antifertility Action of Copper Copper is taken up by the endometrial epithelium and superficial stromata Progestational proliferation is severely inhibited and estrogenic action is interrupted Increase in alkaline phosphatase activity in endometrium and uterine fluid

Biopharmaceutics of Intrauterine Controlled Copper Administration:

Biopharmaceutics of Intrauterine Controlled Copper Administration Copper is released continuously from the IUD by ionization and chelation processes The mean diameter of copper reduces with time accompanied by corrosion and flaking of the metal The antifertility activity of a copper-IUD depends upon the surface area of the copper wire Thus the effectiveness of contraception is associated with the dosage of copper released daily and depends on the concentration of copper in uterine secretion fluids

Biopharmaceutics of Intrauterine Controlled Copper Administration:

Biopharmaceutics of Intrauterine Controlled Copper Administration The mean uterine copper concentration is increased linearly in proportion to the duration of in utero residence of the IUD Uptake: Partly taken up by endometrium Cu concentration increases in both proliferative and secretory endometria during 1 st 6 months and only the latter after 1 yr of use Endometrial copper levels returned to normal once the devices were removed

Biopharmaceutics of Intrauterine Controlled Copper Administration:

Biopharmaceutics of Intrauterine Controlled Copper Administration Cu is absorbed systemically and deposited in organs such as liver and kidney Effect of Calcium and Protein deposition: IUD left in utero showed development of a ‘corrosion layer’ and ‘encrustation layer’ over the copper wire Corrosion layer: Contained protein and plays an important role in the intrauterine delivery of Cu Encrustation layer: Develops over the former and contained calcium deposit – reduction in release rate of copper

Biopharmaceutics of Intrauterine Controlled Copper Administration:

Biopharmaceutics of Intrauterine Controlled Copper Administration The latter can be reduced by coating the copper wire with polymeric membrane such as collodion Calcification may begin from 6 months of insertion and increases with the duration Excess CaCO 3 resulting in formation of compact impermeable layer impairs the delivery of Cu causing the failure of contraception Increased pregnancy rate in women wearing Cu IUD for more than 24 months

Biopharmaceutics of Intrauterine Controlled Copper Administration:

Biopharmaceutics of Intrauterine Controlled Copper Administration Similar barrier effects were observed due to protein deposition The release of copper from protein-coated IUDs follows a linear Q versus t 1/2 relationship Thus the release of copper from a unit surface area of copper does not solely depend on the copper surface area

Comparison of Copper IUD :

Comparison of Copper IUD 1 st Year Failure per 100 women Recommended Lifespan TCu 380A 0.3 12 years Multiload Cu 250 1.2 3 years Multiload Cu 375 1.4 5 years TCu 200 2.3 3 years Nova T 3.3 5 years

References:

References Novel Drug Delivery Systems by Yie W. Chien ; Pg-596-602 www.fhi360.org You know how it is with nuns. Take out their IUDs, they bounce right back – Dr.Gregory House

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