INTRAUTERINE DRUG DELIVERY SYSTEMS

Introduction.
 Intra Uterine Device (IUD)
It 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. IUDs can show pharmacological
efficacy for about 1-10 years. 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.

 A drug with progestogenic activity is released under controlled circumstances

over an extended period of time and at a concentration necessary for
contraception using an intrauterine drug delivery system (IUDDS).
 Appropriate in vitro test methods that guarantee a predictable in vivo performance
are crucial for safe use because IUDs are intended for the controlled delivery of
hormones, i.e., drugs with a narrow therapeutic index, over a very long period of
time.

Advantages of IUDDS
1. They have a success rate of over 98% in preventing unwanted pregnancy.
2. They possess a long lifespan.
3. If you are breastfeeding, you can use them safely.
4. No medications stop them from working.
5. It provides another contraceptive choice if there is difficulty taking the
hormone estrogen.
6. There is no vaginal bleeding at all or a light regular period after use.
Disadvantages of IUDDS
1. It offers no protection from STIs (sexually transmitted infections).
2. IUDDS is useless in cases of pelvic infection and abnormal uterus shape.
3. It is not recommended if you have endometriosis, heavy periods, or low iron
levels.
4. The chance of an ectopic pregnancy may rise as a result.
5. During insertion and removal, there are risks.
6. IUDDS have the potential to result in systemic contraindications such as
copper allergy, immunodeficiency disorders, immunosuppressive therapy,
Wilson's disease, acute liver disease, liver cancer, and breast cancer,
 particularly for hormonal IUDs, as well as multiple sexual partners for the
patient or her partner.
Anatomy of Uterus:
 The uterus, also known as the womb, has an inverted pear shape. It has a
glandular lining known as the endometrium and is a hollow muscular organ
with thick walls.
 The uterus weighs between 30 and 40 gm and is approximately 7.5 cm long, 5
cm wide at its upper part, and nearly 2.5 cm thick.
 The fundus is the portion of the body that is located above a plane that runs
through the points where the uterine tubes enter, and the body is the portion that is
located below that plane.
 The isthmus, a slight external constriction that marks the point where the
body and cervix meet, is where the body narrows toward the cervix. It is the
short narrowed portion of the uterus located inferior to superior to the cervix
and above the body.
 Uterus consists of mainly 3 parts such as
o Fundus,
o body
o Cervix.

Fundus
 The peritoneum covering the fundus is continuous with that on the vesical and
intestinal surfaces, and it is convex in all directions.
 The margins on the sides are slightly convex.
 Each uterine tube pierces the uterine wall at its upper end.
 The round ligament of the uterus is fixed below and in front of this point, and the
ovary's ligament is attached behind it.
 These three structures are contained within the broad ligament, a fold of
peritoneum that extends from the uterine rim to the pelvic wall.

Body:
 On its way from the fundus to the isthmus, the body gradually narrows. The
peritoneum flattens and covers the vesical or anterior surface, which is reflected
onto the bladder to form the vesicouterine excavation.
 The surface is in contact with the bladder.
 The intestinal or posterior surface is convex transversely and is covered by
peritoneum, which extends down onto the cervix and vagina.
Cervix:
 The cervix is the uterus's lower constricted segment.
 It has a slightly conical shape with a blunted apex that faces backward and
downward, but it is wider in the middle than both above and below.
 The cervix has a firmer consistency than the uterus's body because it is made
of fibrous connective tissue.
 It can move less easily than the body.
 The vagina is divided into an upper, supravaginal portion and a lower,
vaginal portion by the cervix, which protrudes through the anterior wall of
the vagina.
Structure.
 The uterus is composed of three coats like an external or serous, a middle or
muscular, and an internal or mucous.
 The peritoneum gives rise to the serous coat, which covers the vesical surface only
up to the junction of the body and cervix while covering the fundus and the entire
intestinal surface of the uterus.
1. The muscular coat / Myometrium:
 The bulkiest component of the uterus' substance is its muscular coat.
 Myometrium, the muscular middle layer of tissue that makes up the majority of
the organ's bulk.
 It is made up of tightly packed, striped smooth muscle fibers and is very firm.
 During pregnancy, the cells in this layer expand and contract in order to
prepare for the delivery of the fetus.
2. The mucous membrane/ Endometrium:
 The mucous membrane is smooth and firmly attached to the tissue around it.
 The mucous membrane, or endometrium, is the uterus' innermost layer of
tissue.
 It merges with the lining of the cervical canal to completely enclose the
uterine cavity up to the uterus' isthmus.
 Endometrium can be further subdivided into 2 parts:
o Deep stratum basalis:
 little changes during the menstrual cycle and is not shed during
the period.
o Superficial stratum functionalis:
 Oestrogens cause it to multiply, while progesterone causes it to
secrete.
 It regenerates from cells in the stratum basalis layer and sheds
during menstruation.
3. Vessels and Nerves:
 The uterine and ovarian arteries enter the uterus from the hypogastric and
abdominal aorta, respectively.
 The ovarian artery terminates where it meets the uterine artery, forming an
anastomotic trunk from which branches supply the uterus in a circular pattern.
 The veins are large in comparison to the arteries.
 They come to an end in the uterine plexuses.
 The arteries in the impregnated uterus transport blood to, and veins away from, the
placental intervillous space.
 The nerves branch off the hypogastric and ovarian plexuses, as well as the third
and fourth sacral nerves.

Development of Intrauterine Device (IUD).

 Intrauterine Device (IUD) is a small object that is inserted through the cervix
and placed in the uterus to prevent unwanted pregnancy.
 IUDs typically consist of a small, flexible plastic frame with a small string
hanging down into the upper vagina.
 During the act of sexual contact, the IUD is not visible.
 Depending on the type, IUDs can last 1 to 10 years.
 To stop fertilization, they interfere with sperm and egg motion.
 Additionally, they alter the uterine lining and stop the fertilized egg from
implanting.
 IUDs are 99.2–99.9% effective at preventing pregnancy.
 They are not able to fend off sexually transmitted diseases like HIV/AIDS.
 Insertion of an IUD is very simple, usually painless and takes only about 5 to
10 minutes.
 Advantages of IUDs.
1. It has a great deal of success in preventing pregnancy.
2. It is affordable.
3. Sex is not disrupted.
4. It doesn't need a partner to participate.
5. It's functional for a protracted period of time.
6. It is a birth control option that can be used in an emergency.
7. An IUD offers cost-effective long-term contraception for three to five years.
Disadvantages of IUDs.
1. Sexually transmitted infections (STIs) are not prevented.
2. It may increase the chances of ectopic pregnancy (pregnancy outside the
uterus).
3. It may result in more painful and heavier bleeding.
4. Cramping and discomfort happen during insertion and for 24-48 hours
afterwards.
5. Both insertion and removal involve risks.
Time of using an IUD.
 An IUD is usually inserted during a menstrual period, when the cervix is
slightly open and pregnancy is least likely to occur.
 There is however a greater chance of expulsion if a device is introduced early
in the cycle because the uterus can squeeze the device back out.
 Therefore, the best time for insertion is just after a period.
 However, an IUD may be inserted at any time.
 The best timing for IUD insertion for women in different situations is given as
follows,
 Types of intrauterine systems:
 Most widely used IUDs are as following,
1. copper-bearing IUDs:
 These are made of plastic with copper sleeves and copper wire on the plastic,
such as TCu-380A and MLCu-375
2. Hormone-releasing IUDs:
a. These are made of plastic and steadily release small amounts of progesterone
or other progestin hormones, such as LNG-20 and Progestasert.
3. Inert or non medicated IUDs:
. These are made of plastic or stainless steel only, such as Lippes Loop and
Chinese stainless steel rings.

1. Copper IUDs
o Copper wire or copper sleeves are put on the plastic frame
(polyethylene frame).
o Examples include Copper T, CuT380A, Multiload 375 etc.
 o The various types of Copper IUDs differ from each other by the amount of
copper.
o The initial Copper IUDs were wound with 200-250 mm2 wire
(CopperT 200).
o The modern copper containing devices contain more copper and a part
of copper in the form of solid tubal sleeves rather than wire.
o This increases the efficacy and lifespan (Cu T-380 A).

 Mechanisms of action:
 The copper IUD functions as a contraceptive (inhibiting fertilization).
 CuT-380A IUD inhibits sperm motility and block activation of acrosomal
enzymes in the sperm head needed for the sperm to penetrate through the
zona pellucida to enable union of the gametes.
 The copper slows down the movement of sperm within the woman's uterus
and so prevents them from reaching the fallopian tubes and fertilizing the
egg.
 The device also stimulates a strong reaction in the wall of the uterus, which
prevents implantation of the egg (even if it is fertilized).
Advantages of the Copper T 380A IUD:
1. IUDs are a highly effective, secure, and long-acting method of birth control.
2. It only requires one decision from the woman to use it, unlike the pill,
condoms, and spermicides, which require decisions for each act of sexual
activity.
3. Copper-bearing or inert IUDs have no negative hormonal effects.
4. It is the best option for people taking antiepileptic or antituberculosis
medications because it does not interact with any other drugs the client may
be taking.
5. The IUD works best for people who want a quick and long-lasting reversible
method.
6. Additionally, the Copper T 380A IUD aids in preventing ectopic pregnancies.
7. Lactating women may use the copper T 380A IUD because it has no effect on
the quantity or quality of breast milk.
Disadvantages of the Copper T 380A IUD:

1. Pelvic inflammatory diseases (PID):

a. The risk of PID development is one of the main issues with IUD use.
b. At the time of insertion, there is the greatest risk of pelvic infection related to
IUD use.
2. Menstrual problems:
. IUD use may be accompanied by increased menstrual pain (dysmenorrhoea).
3. Expulsions:
. It's possible for an IUD to exit the uterus without the woman's knowledge.
a. This happens more frequently when the IUD is put in place soon after giving
birth, when there is abnormally heavy menstrual flow, or when there is severe
dysmenorrhoea (painful cramping during the menstrual cycle).
4. Pregnancy:
. When an IUD is present, spontaneous abortion occurs in 50% of intrauterine
pregnancies.
a. Early pregnancy IUD removal reduces spontaneous abortion rates to about
25%.

2. Hormone-Releasing IUDs:
 Levonorgestrel (LNG), a progestin, is a hormone that is released in small
amounts by hormonal IUDs.
o Brand names Skyla, Liletta, and Mirena
 The main mechanism of action is to render the uterus' interior lethal to
sperm.
 Their primary purpose is not to thin the endometrial lining or possibly hinder
implantation.
 Once pathologic causes of menorrhagia, such as uterine polyps, have been
ruled out, they can be used to treat menorrhagia (heavy menses) because they
thin the endometrial lining, which reduces or even stops menstrual bleeding.
 When Mirena is used compared to other very-low-dose progestogen-only
contraceptives, systemic progestin levels are significantly lower. The progestin
released by hormonal IUDs primarily acts locally.
 e.g
o Progestasert:
  It is a T shaped IUD made of ethylene and vinyl acetate
copolymer containing titanium dioxide.
 The vertical stem contains a reservoir of 38 mg progesterone
together with barium sulfate dispersed in silicone fluid.
 The progesterone is released at the rate of 65 µg per day.
o LNG-releasing IUDs:
 There are two similarly sized IUDs with 52 mg LNG and one is
smaller with 13.5 mg LNG.
 The release rates of LNG were measured at different times
following the placement, which initially led to some confusion in
naming conventions.

3. Inert or non medicated IUDs:

 These IUDs do not have a bioactive component.

 The Lippes Loop, which can be inserted through the cervix with a cannula
and takes on a trapezoidal shape inside the uterus, is one example of an inert
material that is used to make it. Stainless steel is used in the stainless steel
ring (SSR), a flexible ring of steel coils that can deform to be inserted through
the cervix.
 It has similar side effects to copper IUD and is less effective than hormonal or
copper IUD.
 Inducing a localized foreign body reaction serves as the mechanism of action,
making the uterine environment hostile to both sperm and embryo implantation.
 These IUDs have higher rates of preventing pregnancy after fertilization, instead
of before fertilization, compared to copper or hormonal IUDs.
 Inert IUDs are not approved for use in the United States, UK, or Canada.
 But in China, these IUDs are the most common form of contraception.
 Applications of IUD:
1. IUD is effectively useful in contraception similar or better than female
sterilization.
2. IUDs are safe to use for many years.
3. They may even remain somewhat effective past their recommended end
date.
4. It provides long term contraception.
5. For people with severe health conditions that make pregnancy
dangerous, an IUD can be life-saving.
6. IUDs can be safely placed immediately after abortion or 6 weeks
7. postpartum with high contraceptive benefits.
8. Copper IUD is recommended as the most effective option for emergency
contraception.
9. IUDs include the treatment of menorrhagia, anemia, dysmenorrhea and
pelvic pain associated with endometriosis, and endometrial protection
during hormone replacement.