Intrauterine Drug Delivery System - Intra Uterine Devices

Intrauterine Drug Delivery System

Intra Uterine Devices


v  Introduction

Ø  Contraception

Ø  Anatomy of uterus

Ø  Menstrual cycle

Ø  Desirable features of intra vaginal DDS

v  IUD’S

v  Development of IUD’s

v  Types of IUD’s

1)      non medicated

2)      medicated         

a) Copper bearing IUD

              b) Hormone releasing IUD



Ø  It is the method which results into temporary or permanent loss of capability to reproduce or conceive a young one.

Ø  In simple words it is the opposite of conception.

Ø  There are 2 types of contraception: Temporary and permanent.

Ø  Temporary contraception: It is a method or lifestyle that ensures reversible infertility for stipulated period of time depending on the subject. e.g. IUD’s, oral contraceptive pills, condoms etc

Ø  Permanent contraception: It is the method or technique adopted to give lifelong acquired inability to reproduce, but it is not the loss of sense or loss of sexual desire.

Ø  e.g. ovarectomy, uterectomy, vasectomy, etc.

Anatomy of uterus

l  The uterus is a pear shaped, thick-walled, muscular organ suspended in the anterior wall of pelvic cavity.

l  In its normal state, it measures about 3 inches long and 2 inches wide.

l  Fallopian tubes enter its upper portion, one on each side, and the lower portion of the uterus projects into the vagina.

l  The uterine cavity is normally triangular in shape and flattened anterio-posteriorly.

The wall of the uterus consists of 3 layers:

1. Endometrium- Inner coat of the uterine wall and is a mucous membrane. It consists of epithelium lining and connective tissue.  Epithelium consists of non-cornified stratified sqamous epithelium, and lamina propria.

Squamous epithelium sub-divided into 4 layers:  Superficial - large, flat cells.

Intermediate – larger flatter nucleated cells Parabasal – polyhedral cells

Monolayer – cuboidal basal cells closely opposed to basement membrane.

Connective tissue consists of two types of arteries which supply blood to the endometrium- straight arteries supply the deeper layer; the coiled arteries supply the superficial layer.

2.       Myometrium- Thick, muscular middle layer made up of bundles of interlaced, smooth muscle fibers emmbeded in connective tissue. It is Sub-divided into 3 ill-defined, intertwining muscular layers containing large blood vessels of uterine walls.

3.       Peritoneum- External surface of the uterus, which is attached to the both sides of the pelvic cavity by broad ligaments through which the uterine arteries cross.


Human female’s fertility period, extends from puberty at about 13 years to about 45-50 years. The menstrual cycle consists of 3 phases:

l  Follicular or proliferating phase

l  Luteal or secretory phase

l  Menstrual or bleeding phase


  1. It lasts for 14 days.
  2. Follicle stimulating hormone (FSH) stimulates the growth of ovarian follicle and maturation of the primary oocyte in this follicle.
  3. FSH stimulates the follicles to secrete estradiol which on attaining a certain concentration in blood inhibits FSH secretion and stimulates Leuteinising hormone (LH) secretion.
  1. The LH induces the Graafian follicle to burst and eject its eggs into the fallopian tube,a process called ovulation.
  1. Estradiol also stimulates the uterus to prepare for the implantation nourishment of the foetus likely to arrive after ovulation.
  2. Vascularization of uterus increases and the lining of fallopian tubes is thickened. The ciliary movements also increase and prepare the fallopian tubes to convey the ovum to the uterus.


  1. It lasts for 10 days
  2. High levels of LH and prolactin hormone stimulate follicular cells of empty graafian follicle to form yellow colour body called corpus luteum, which in turn secretes progesterone.
  1. Progesterone regulates the hypertropy of endometrium for proper implantation of foetus.
  1. Luteal phase stimulates the endometrial glands to secrete a nutriant fluid for the foetus, hence it is called the secretory phase.


  1. If fertilization does not occur, high concentration of progesterone in blood inhibits the release of LH.
  2. Reduction in LH levels leads to the degeneration of corpus luteum and a consequent fall in progesterone level in blood.
  3. The uterine lining dies due to deficiency of progesterone and is sloughed off. Blood vessels rupture, causing bleeding, this process is called the menstrual flow and continues for 3-5 days.
  4. The basal part of the endometrium remains intact for next cycle.
  5. Lowered levels of progesterone and estradiol due to degeneration of corpus luteum causes the release of FSH which initiates new cycle.


l  Functionally effective and aesthetically pleasing to the patient.

l  The system must be non-irritant and non-interfering with normal physiological processes.

l  Sustained release for chronic treatment.

l  Commercially, cost should be low and manufacturing should be easy.



l  IUD’s are medicated devices intended to release a small quantity of drug intouterus in a sustained manner over prolonged period of time.

3 most popular methods:

l  Oral contraceptive pills

l  Condoms or diaphragms

l  Intrauterine device


Methods of  contraception




MBR deaths/  l000 births











Condom or  diaphragm







Oral pills















An Intrauterine Device (IUD) is a small object that is inserted through the cervix and placed in the uterus to prevent pregnancy.

A small string hangs down from the IUD into the upper part of the vagina.

The IUD is not noticeable during intercourse.

IUD’s can show pharmacological efficacy for about 1-10 years.

M O A: They work by changing the lining of the uterus and fallopian tubes affecting the movements of eggs and sperm and so that fertilization does not occur.

Development of IUD’s

Development of IUD’s began in the 1920s, with the first generation of IUD’s constructed from silkworm gut and flexible metal wire. Eg-  Grafenberg star and Ota ring.

Fell into disrepute because of the difficulty of insertion, the need for frequent removal as a result of pain and bleeding.

Subsequently, plastic IUD’s of varying shapes and sizes were made available.

Various inert, biocompatible, polymeric materials — such as polyethylene and silicone elastomer — were widely used to construct IUD’s.

These devices cause more endometrial compression and myometrial distension, leading to uterine cramps, bleeding, and expulsion of IUD’s.

Researchers developed IUD’s in last 30 years with aim - to add  antifertility agents to more tolerated, smaller devices, such as the T-  shaped device, to enhance effectiveness; or antifibrinolytic agents, such  as e-aminocaproic acid and tranexamic acid to larger IUD’s to minimize  the bleeding and pain.

Tatum developed a T – shaped device to confirm to the better contours of uterus. This reduced side effects significantly.

Zipper 1968 added contraceptive metals (Cu) and Doyle and Clewedeveloped progestin – releasing IUD’s.

This development initiated a new era of R & D for long term I.U

       contraception, leading to generation of recent IUD’s– the medicated


Copper bearing IUD’s, such as Cu – 7 and progesterone releasing IUD’s such as Progestasert thus evolved.



a) Non-medicated IUD’s:

These IUD’s exert their contraceptive action by producing a sterile inflammatory response in the endometrium by its mechanical interaction. These do not contain any therapeutic agent.

e.g. ring shaped IUD’s plastic IUD’s, lippes loop, Dalkon shield, Saf-  T-Coil.

b) Medicated IUD’s:

These IUD’s are capable of delivering pharmacologically active antifertility agents.

e.g. copper bearing IUD’s, progesterone releasing IUD’s.

Non – medicated IUD’s

These IUD’s do not contain any therapeutically active agent.

These prominantly make use of metal or plastic rings and coils.

e.g. Dalkon shield, Lippes loop, Saf - T- coil.

Rings of stainless steel have mechanical effects on the uterus leading to contraception.

Plastic rings also act as mechanical barrier for sperms and eggs so they don’t fuse.

Plastic rings are made from sterile materials such as polyethylene and polypropylene

Non medicated IUD’s have vanished from market.  Because of one or more following reasons:

l  Newer devices that are safer and effective.

l  Irregularities in menstrual bleeding.

l  Discomfort and lower patient compliance

l  Cases of pelvic inflammatory diseases (PID).

l  They show higher rates of pregnancies.

Medicated IUD’s:

v  Copper bearing IUD’S

v  Hormone releasing IUD’S


       This device uses copper wire wound to the stem.

       The device is made of T shaped polyethylene plastic.

       There are various grades as per the  surface area of the Cu-wire such as  Cu-T-30, Cu-T-200, Cu-T-380


       Low conc.- Spermatocidal & Spermatodepressive

       Contraceptive Effectiveness is more.

       Pregnancy rate –reduced to 5%

       e.g.        cu –T-200, cu-T-30, cu-T-380, Cu-T-220

       Copper wire thickness –0.2-0.4 mm

Mechanism of action

Clinical effectiveness of Cu-T and Cu-7

Antifertility Action of Copper

l  In high concentration copper is cytotoxic. It enhance the spermatocidal and spermato- depressive action of an IUD.

l  Cupric ion (Cu++) is a competitive inhibitor of progesterone and to lesser effect estrogen.

l  Evoke sterile inflammatory response in the endometrium.

Release of Copper from the device

                       The release is linear by chelation, ionization, and corrosion over the period of 12 years.

       Release rate is directly proportional to the surface area of exposed Cu.

       e.g. Cu-T-380A

       It has a surface area of 380

       Composed of polyethylene T with 176mg Cu wire on stem and 66.5mg on the arms.

       Approved by FDA for 10 year use.

       The Cu-T-380 Ag IUD differs only at Cu has Ag core that slows the corrosion rate.

Side effects

n  Menstrual problems. About 12% of women have the Copper T 380-A IUD removed because of increased menstrual bleeding or cramping.

n  Perforation. In 1 out of every 1,000 women, the IUD will get stuck in or puncture (perforate) the uterus. Although perforation is rare, it almost always occurs during insertion.

n  Expulsion. About 2% to 10% of IUD’s are expelled from the uterus. This usually happens in the first few months of use.  Expulsion is more likely when the IUD is inserted right after childbirth or in a nulliparous woman (a woman who has never given birth to a child before).


n  Doyle and Clewe first initiated the use of hormone releasing IUD’s.

n  Scommegna et al in 1970 carried human testing using conventional IUD having contraceptive steroids.

n  A T-shaped progesterone releasing IUD having vertical limb embedded with drug-containing silicone capsule was evolved.

n  Coated with polymer for achieving slower release.


n  Enhance uterine retension

n  Show slowly releasing steroids

n  e.g. Melengestrol acetate.


n  Suspension of Progesterone microcrystal àSilicon medial fluid à Ethylene- Vinyl acetate copolymer (EVA)

n  Release rate-65 mg/ day for one year.

Progesteron releasing IUDs

Progestesert :

n  A novel progesterone (pg) releasing IUD.

n  The device has a solid poly EVA (ethyl vinyl acetate) side arms core in the silicone oil with BaSo4.

n  Dimensions-0.25mm thick, pg is released by diffusion through rate limiting membrane.

n  Loaded with 38mg of Pg, release rate is 65 mcg/day

n  Approved by USFDA in 1975 for 12 month contraceptive use

n  Preg. Rate 1.8/100 for parous and 2.5/100 for nulliparous.

n  Does not inhibit ovulation but interfere with implantation in endometrium, thickening of cervical mucus.

n  Intrauterine administration was compared with oral delivery and sub-cutanous injection. Progesterone administered I U shows 45 times greater bioavailability than the other 2 routes.

n  Apparently the endometrium tissue is extremely effective for progesterone absorption.


Increased effectiveness, lower menstrual blood flow, and decreased dysmenorrhea.


Need to be replaced yearly, intermenstrual bleeding, ectopic pregnancies?

38 mg of progesterone microcrystals (and barium sulfate) suspended in silicone oil

Antifertility action of progesterone releasing IUDs:

They diminish sperm transport through the cervix to the oviduct by increasing the thickness of the cervical mucus.

Steroid releasing devices induce progesteronal changes that result in endometrial gland atrophy and inhibit further development of the ova.

Endometrial hypermaturation is unfavorable for implantation of a blastocyst. This is associated with decidual formation induced by progesterone.

Effect of estrogen-progesterone system is related to the presence of a membrane electrical potential that inhibits the ovum-endometrium contact before the occurrence of implantations.

Levonorgesterol releasing IUD

n  These carry levonorgesterol releasing device. It is an intrauterine system that has sleeves of levonorgesterol 52 mg around its stem.

n  It is composed of a polyethylene stem covered by matrix Silastin: LNg (2:1).

n  Releasing 20 mcg/day and lasting for at least 5 years. Initial fast release then at 60 % drug release rate reduces to 16mcg/day.

n  Suppresses endometrium and ovulation.

n  Also, unlike other IUDs, it may reduce the risk of (PID).

Mode of action :

n  Prevents fertilization by damaging or killing sperm and making the mucus thick and sticky, so sperm can't get through to the uterus.

n  It also keeps endometrium from growing very thick, making lining a poor place for a fertilized egg to implant and grow.

n  It may relieve irregular menstrual bleeding and cramping.

Disadvantages of LNg IUD

n  It may cause noncancerous (benign) growths called ovarian cysts, which usually go away on their own.

n  It can cause hormonal side effects, such as breast tenderness, mood swings, headaches, and acne. When side effects do happen, they usually go away after the first few months.



          puerperal sepsis or immediate post septic  abortion

          distorted uterine cavity (congenital or acquired)

          unexplained vaginal bleeding

          suspected genital malignancy

          genital tuberculosis

          active Pelvic Inflammatory Disease (PID)


          Copper T 380 A IUD (ParaGard) is effective for at least 12 year

          Copper T IUD (ParaGard) and Levonorgestetrel IUD (Mirena) are the two most effective reversible methods of birth control.

  • Only 1 out of 100 women using a Copper T for 12 years will become pregnant.
  • The copper IUD prevents ectopic pregnancies.
  • This contraceptive is very cost effective (inexpensive) over time.
  • Use of an IUD is convenient, safe & private.
  • All you have to do is check for the strings each month.
  • The ParaGard IUD may be used by women who cannot use estrogen–containing birth control pills, patches or vaginal ring including breastfeeding women.
  • The IUD may be inserted immediately following the delivery of a baby or immediately after an abortion.
  • Some studies of IUDs have shown a decreased risk for uterine cancer. There is also some evidence that IUDs protect against cervical cancer.


l  There may be cramping, pain or spotting after insertion.

l  The number of bleeding days is slightly higher than normal and you may have somewhat increased menstrual cramping. If your bleeding pattern is bothersome to you, contact your doctor. There are medications which may give you a more acceptable pattern of bleeding and cramping.

l  The IUD provides no protection against sexually transmitted infections. Use condoms if there is any risk.

l  There is a higher initial cost of insertion. However, after 2 years, it is the most cost-effective contraceptive method.

l  The IUD must be inserted by a doctor, nurse practitioner, nurse midwife or physician’s assistant.

l  A very small percentage of women are allergic to copper.

l  A small percentage of IUDs may be expelled by a woman’s body within the first few months due to an improper fit.

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