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Intrauterine Drug Delivery System
Intrauterine Drug Delivery System
Intrauterine Drug Delivery System
org
CONTENTS
Introduction
Contraception
Anatomy of uterus
Menstrual cycle
IUD’S
Development of IUD’s
Types of IUD’s
1) non medicated
2) medicated
TERMS
CONTRACEPTION: (def)
It is the method which results into temporary or permanent loss of capability to reproduce or conceive a young
one.
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
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.
Anatomy of uterus
The uterus is a pear shaped, thick-walled, muscular organ suspended in the anterior wall of pelvic cavity.
In its normal state, it measures about 3 inches long and 2 inches wide.
Fallopian tubes enter its upper portion, one on each side, and the lower portion of the uterus projects into the
vagina.
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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.
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.
MENSTRUAL CYCLE
Human female’s fertility period, extends from puberty at about 13 years to about 45-50 years. The menstrual cycle
consists of 3 phases:
FOLLICULAR PHASE
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.
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4. The LH induces the Graafian follicle to burst and eject its eggs into the fallopian tube,a process called ovulation.
5. Estradiol also stimulates the uterus to prepare for the implantation nourishment of the foetus likely to arrive
after ovulation.
6. 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.
LUTEAL PHASE
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.
4. Luteal phase stimulates the endometrial glands to secrete a nutriant fluid for the foetus, hence it is called the
secretory phase.
MENSTRUAL 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.
The system must be non-irritant and non-interfering with normal physiological processes.
DEFINITION
IUD’s are medicated devices intended to release a small quantity of drug intouterus in a sustained manner over
prolonged period of time.
Condoms or diaphragms
Intrauterine device
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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.
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
• IUD’s.
Copper bearing IUD’s, such as Cu – 7 and progesterone releasing IUD’s such as Progestasert thus evolved.
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LOCATION OF IUD
TYPES OF IUD
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:
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:
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Medicated IUD’s:
Copper bearing IUD’S
• There are various grades as per the surface area of the Cu-wire such as Cu-T-
30, Cu-T-200, Cu-T-380
• Cytotoxic
Mechanism of action
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Antifertility Action of Copper
In high concentration copper is cytotoxic. It enhance the spermatocidal and spermato- depressive action of an
IUD.
Cupric ion (Cu++) is a competitive inhibitor of progesterone and to lesser effect estrogen.
• The release is linear by chelation, ionization, and corrosion over the period of 12 years.
• e.g. Cu-T-380A
• Composed of polyethylene T with 176mg Cu wire on stem and 66.5mg on the arms.
• The Cu-T-380 Ag IUD differs only at Cu has Ag core that slows the corrosion rate.
Side effects
Menstrual problems. About 12% of women have the Copper T 380-A IUD removed because of increased
menstrual bleeding or cramping.
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.
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).
Scommegna et al in 1970 carried human testing using conventional IUD having contraceptive steroids.
A T-shaped progesterone releasing IUD having vertical limb embedded with drug-containing silicone capsule was
evolved.
Objectives
Formulation:
Suspension of Progesterone microcrystal Silicon medial fluid Ethylene- Vinyl acetate copolymer (EVA)
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The device has a solid poly EVA (ethyl vinyl acetate) side arms core in the silicone oil with BaSo4.
Does not inhibit ovulation but interfere with implantation in endometrium, thickening of cervical mucus.
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.
Advantages:
Disadvantages:
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.
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Releasing 20 mcg/day and lasting for at least 5 years. Initial fast release then at 60 % drug release rate reduces
to 16mcg/day.
Mode of action :
Prevents fertilization by damaging or killing sperm and making the mucus thick and sticky, so sperm can't get
through to the uterus.
It also keeps endometrium from growing very thick, making lining a poor place for a fertilized egg to implant and
grow.
It may cause noncancerous (benign) growths called ovarian cysts, which usually go away on their own.
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.
Contraindications
• pregnancy
• genital tuberculosis
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• 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 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.
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.
The IUD provides no protection against sexually transmitted infections. Use condoms if there is any risk.
There is a higher initial cost of insertion. However, after 2 years, it is the most cost-effective contraceptive
method.
The IUD must be inserted by a doctor, nurse practitioner, nurse midwife or physician’s assistant.
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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