The device which is used in the intrauterine drug delivery system is known as an Intrauterine device (IUD) (2). IUDs or intrauterine devices are small artificial objects or devices inserted into the uterus to prevent the occurrence of pregnancy by disrupting the fertilization process as a result of sexual intercourse. They have gained popularity in recent times and are one of the most effective methods of birth control in terms of long-term contraception. It can be easily installed and is flexible. These devices are usually small in size and inserted through the cervix. IUDs reduce the need for abortion with unwanted pregnancies by preventing the effective movement of eggs and sperm. However, it cannot confirm the spread of STIs or STDs such as HIV, gonorrhoea, etc Topics covered Introduction Advantages Disadvantages Development of intra uterine devices (IUDs) Applications References

1. INTRAUTERINE
DRUG DELIVERY
SYSTEM
Presented by
Aloysia Cardoso
Roll no.1
M.pharm Pharmaceutics
Semester II
PES RTPCOP , Farmagudi-Goa

2. CONENTS
Introduction
Advantages
Disadvantages
Development of intra uterine devices (IUDs)
Applications
References

3. INTRODUCTION
– The uterus (womb) is a pear‐shaped dynamic muscular organ that is responsible
for a variety of functions such as gestation (pregnancy), menstruation, labor,
and delivery .
– The uterine drug delivery system works with a variety of medical or non-medical
devices that perform the act of contraception in the uterus continuously for a
prolonged range of time. In recent times they are mainly used for family
planning.
– The device which is used in the intrauterine drug delivery system is known as an
Intrauterine device (IUD)

4. INTRODUCTION
– IUDs or intrauterine devices are small artificial objects or devices inserted into
the uterus to prevent the occurrence of pregnancy by disrupting the fertilization
process as a result of sexual intercourse.
– They have gained popularity in recent times and are one of the most effective
methods of birth control in terms of long-term contraception. It can be easily
installed and is flexible.
– These devices are usually small in size and inserted through the cervix. IUDs
reduce the need for abortion with unwanted pregnancies by preventing the
effective movement of eggs and sperm. However, it cannot confirm the spread
of STIs or STDs such as HIV, gonorrhoea, etc.

5. INTRODUCTION
– The length of the IUD is about 3cm. The IUD is developed in various shapes out of
which the well-known is the T-shaped device and copper-T that is coated with
copper metal.
– Copper has the spermicidal activity this inserted IUDs effects for five years. Some
IUDs are also prepared by using hormones like progesterone instead of copper but
they have to replace once every year.
– IUDs are inserted into the upper tract of the vagina with the help of the attached
strings. (2)
– Before the insertion of the IUDs the expert should examine the pelvic region to
measure the shape, shape, and position of the uterus, and then an antiseptic
solution should be applied to the cervix and inserted into the uterus.

6. ADVANTAGES
– Advantages
– Lower probability of death and risk compared to oral pills.
– Doesn’t alter or affect the natural hormonal balance.
– Offers long-term birth control around 2-10 years.
– Doesn’t interfere with sexual activity or coitus or libido
– Higher patient compliance in terms of dosing frequency and adherence.
– Can be used by Nulliparous women
– Action can last for a longer time if not removed in between.
– Do not interact with body organs. Can be easily fitted and removed.

7. ADVANTAGES
– Better alternative contraceptive if the patient can’t take pills or has a weak memory.
– Immediate onset of action is seen
– IUDs can be used by breastfeeding or lactating women
– Can be used by women on different medication therapies (diabetes, cancer) except
hormonal contraception
– Reversible as fertility returns after discontinuation
– IUDs can be used by women at any age.
– Effective and simple to use.
– Cost-effective i.e. no ongoing cost after initial insertion.
– Long term effect preferably up to 12 years e.g. copper

8. DISADVANTGES
– Higher rate of birth compared to oral pills
– Insertion requires a qualified medical practitioner
– Can’t prevent risks of sexually transmitted infections(STIs)
– Menorrhagia, dysmenorrhea, and polymennorhea are major reasons for IUD
discontinuation
– May increase the likelihood of ectopic pregnancy (pregnancy outside the uterus)
– Higher risks of uterine infection or perforation if not inserted properly.
– Increased chances of pregnancies if not administered properly
– Insertion can be painful or can worsen menstrual cramps at times

9. DISADVANTGES
– Copper IUDs avoided in case of Wilson’s disease
– Hormonal IUDs not recommended for liver disease or breast cancer
– Risk of expulsion within the first year
– Irregular bleeding in initial stages
– Can’t be used in case of pelvic infection or heavy bleeding or endometriosis.
– Side effects include nausea, vomiting, headaches, or weight gain.
– Can cause unwanted allergies
– Risk for preterm delivery if you get pregnant with an IUD, particularly if it's left in
place.

10. DEVELOPMENT
OF IUDS
– The development of intrauterine contraceptive devices began in the 1920s with the
first generation of IUDs made of silkworm gut and flexible metal wire, such as the
Grafenberg star and the Ota ring. These devices have been withdrawn due to the
complexity of the procedure to include the need for repeated removal due to pain
and bleeding, and other serious problems.
– Many plastic IUDs of various types and sizes are made from a variety of inert
materials, biocompatible polymeric materials, including polyethylene,
polypropylene, ethylene-vinyl acetate copolymer, and silicone elastomer, are
available. Intrauterine devices (IUDs) were available as another method of
contraception for women experiencing adverse reactions when taking oral
contraceptives. These devices cause more endometrial compression and
myometrial distension, leading to uterine cramps, bleeding, and expulsion of IUDs.

11. DEVELOPMENT OF IUDS
– The first plastic IUD, the Margulies Coil or Margulies Spiral, was introduced in
1958. This device was somewhat large, causing discomfort to a large proportion
of women users, and had a hard plastic tail, causing discomfort to their male
partners. The Lippes Loop, a slightly smaller device with a monofilament tail, was
introduced in 1962 and gained in popularity over the Margulies device. The
stainless steel single-ring IUD was developed in the 1970s (3).
– The T-shaped polyethylene tool was later developed by Tatum which was smaller
in size to better fit the uterine lining which eventually overcame the problems
listed above but unfortunately showed a few pregnancies.
– This development has bloomed in a new era of research and development of
long-term contraceptive methods, leading to the development of a new
generation of lUDs, of lUDs, the medicated intrauterine contraceptive devices.
Copper-bearing lUDs, such as Cu-7, and progesterone-releasing lUDs, such as
Progestasert also evolved.

12. DEVELOPMENT OF IUDS
– An IUD should be designed such that the device should adhere to the boundaries of
the cervical spine, rather than the endometrium contour and myometrium are
compliant with the device when the uterine cavity is empty.
– The endometrium area is separated from each other only by a thin layer of mucus
and other secreted fluid of the endometrial glands and tubal epithelium
– . As the contraction of the myometrial fibres, the wall of the uterus becomes firm
and short, and in response, the endometrial cavity becomes smaller in all sizes.
– As the cuts grow, the lateral walls of the uterus become closer and the hole takes
the form of the T shape. Thus an intrauterine device in the shape of a T can easily
conform to the shape as well as the size of the endometrial cavity, causing minimal
myometrial distension and endometrial compression.

13. DEVELOPMENT OF IUDS
– Preliminary clinical data have shown that a T-shaped IUD results in approximately
one-fifth of pain and bleeding episodes such as the popular Lippes loop IUD.
– In addition, the eviction rate was found to be only part of the standard Lippes loop.
This low incidence of T-shaped IUD is limited due to two differences T-formation
features:
– (i) T-shape is well aligned with the cervical spine, reducing myometrium distortion
– (ii) the removal and replacement of The IUD shaped end of the endometrial cavity
is resisted by three points of contact between the device and the walls of the
endometrium

14. DEVELOPMENT OF IUDS
– There are 2 types of IUDs
– Medicated IUDS
– Medicated lUDs are those lUDs that are capable of delivering pharmacologically
active antifertility agents e.g. copper-bearing IUDs, progesterone releasing IUDs.
– Non-Medicated IUDs
– The non-medicated IUD exerts its contraceptive action by producing a sterile
inflammatory response in the endometrium by its mechanical interaction. They do
not exert any pharmacological or therapeutic action in the body. They are inert in
nature with no medical response-producing ability. These are made of plastic or
stainless steel only. The non-medicated IUDs currently available for intrauterine
contraception consist of ring-shaped IUDs made of stainless steel or plastic e.g. the
Lippes Loop Saf-T-Coil or Chinese stainless steel rings.

15. DEVELOPMENT OF IUDS
– Medicated IUDs
Two classes of medicated lUDs are available:
 Non-hormonal IUDs/Copper-Medicated IUDs
 Hormonal IUDs / Progesterone containing IUDs

16. Non-hormonal IUDs/Copper-
Medicated IUDs
– These are made of plastic with copper sleeves and copper wire on the plastic, such
as TCu-380A and ML Cu-375.
– The effect of copper ions on the binding of steroid hormones to receptors was
investigated in the rabbit's uterus. The results showed that cupric ion (Cu2 +) is a
competitive inhibitor of steroid-receptor interactions by acting on receptor sites by
differentiating and binding to the receptor macromolecule.
– The progesterone receptor is more sensitive to cupric ions than the estrogen
receptor. These IUDs contain polypropylene or polyethylene plastic support number
7 or letter T with a certain amount of earth metal and metal around them.
– Copper wire thickness –0.2-0.4 mm

17. Copper-Medicated IUDs
– The T-shape IUD is popular because it adheres to the cervical spine and resists
migration and circulation within the uterus and uterus and resists migration and
spread within the uterus and rupture.
– The machine has two flexible arms that fold down so that they can fit in and grow
into a T-shape when inside the uterus. With open configuration, this device is 36 mm
long and 32 mm wide (e.g., CU-7, G. D. Searle & Co.)
– The vertical stem of the wound is a thin copper cord and the two horizontal arms also
have a copper sleeve. Under a straight trunk, a 3 mm lamp has monofilament
polyethylene cords that facilitate the removal of the object.
– The device is active for 12 years. The various copper IUDs differ from each other by
the amount of copper present in them.

18. Copper-Medicated
IUDs
– The initial copper IUDs were wound around 200-250 mm2 i.e. Copper T-200. The
modern copper-containing devices contain more copper and a part of copper in the
form of solid tubal sleeves rather than wire. This increases the efficacy and lifespan
e.g. CuT-380 A
– CuT 380A is a T-shaped device with a polyethylene frame holding 380mm2 of the
exposed surface of copper .
– The IUD frame contains barium sulfate thus making it radio-opaque.it inhibits the
sperm motility and blocks activation of the acrosomal enzyme in the sperm head
needed for sperm to penetrate through the zona pellucida to enable a union of
gametes.
– The copper slows down the movement of sperm within the women’s uterus to
prevent them from reaching the fallopian tube and fertilizing the egg.

19. Copper-Medicated
IUDs
– The device also stimulates a strong reaction in the wall of the uterus which prevents
implantation of the egg even if it is fertilized by changing the endometrial lining.
– in short, it interferes with the reproductive process before ova reaches the uterine
cavity.it also thickens the cervical mucus and interferes with the ability of sperm to
pass through the uterine cavity.
– The CuT-380A IUD is placed into the uterus using a two-handed technique. The IUD
arms are loaded manually pointing downward into the insertion tubing after uterine
sounding has verified that the woman’s uterus is in the appropriate depth (6–9 cm)
– The loaded IUD tubing should be advanced directly in one step to the uterine
fundus, and then the arms are to be released. With this approach, the WHO quoted
a perforation rate of 0.6/1,000 placements.

20. Copper-Medicated IUDs
– CuT-380Ag is identical to 380 A except that copper wire on the stem has a silver core
to prevent fragmentation and extend the lifespan of copper
– CuT 380: slim line has copper sleeves flushed at the ends of horizontal arms to
facilitate easier loading and insertion.
– Cu T200: In this copper wire is wounded around the vertical stem, T shaped frame
made of polyethylene, with polyethylene threads (2). Their life span is about three
years and the rate of failure is 3%. They are replaced with more copper with
increased efficacy and life span (Magoon et al., 1982) (2).
– Multiload 375: has 375 mm2 of copper wire wound around its stem. The flexible
arms are designed to minimize expulsions. The multi-load 375 and T cu-380 A are
similar in efficacy and performance. (4)

21. Copper-Medicated IUDs
– Nova T: it is similar to CuT-200, containing 200 m2 of copper. However it has a silver
core to the copper wire, flexible arms, and a large flexible loop at the bottom to
prevent cervical perforations. Nova T or Flexi T 300 IUD is about 98.7per cent
effective in preventing pregnancy. Irena IUD is 99 percent effective in preventing
pregnancy
– Copper-T IUD causes an increase in cervical fluid containing copper ions, enzymes,
prostaglandins, and macrophages that form a violent sperm area and prevent it
from fertilizing the egg. Oocytes and fertilized ova formation.
– Clinical effectiveness of Cu-T and Cu-7 Pregnancy rate Treatment (Months) Cu – T Cu
– 7 Uterus Uterine cavity Copper wine around plastic T Thread for insertion or
removal of the device

22. Hormonal IUDs
– Can be further characterized into progesterone containing IUD or
Levonorgestrel releasing IUD
– Hormonal IUDs work by releasing a small amount of hormone i.e. either
progesterone or Levonorgestrel. The primary mechanism of action is making the
inside of the uterus fatal to sperm. They cause thinning of the endometrial
lining and potentially impair implantation. Doyle and Clewe were the first to
initiate the use of hormone-releasing IUDs. In the year 1970, Scommegna
conducted a human test using a standard IUD containing contraceptive steroid.
T-shaped progesterone releasing an IUD with a vertical stem and a silicone
capsule containing the drug appeared. It is also covered with a polymer for
slow-release discharge.

23. Progesterone releasing IUD
– These IUDs make the cervical mucus thick so that sperm cannot enter the
uterus.
– There is a change in the lining of the uterus to enhance uterine retention which
does not allow pregnancy by slowly releasing steroids.
– Suppression of ovulation is seen and also it prevents the survival of sperm. It
prevents pregnancy for about 5 years by releasing a small amount of
progesterone evenly into the uterus.
– Hormone IUDs are similar to copper T. These devices are T-shaped devices
made of polyethylene frames measuring 32 mm in horizontal and vertical
directions.

24. Progesterone releasing IUD
– There is a silicon reservoir containing levonorgestrel or progesterone scattered on the vertical
shaft, which is further attached to the membrane sleeve to control the rate of ethylene-vinyl
acetate copolymers. Release rate- is approximately about 65 g/ day for one year.
– They can also reduce and prevent menstrual bleeding and are used to treat menopause or
heavy menstruation. The drug released from the hormone IUD acts locally.
– Progesterone releasing IUD shows 45 times more availability than oral and subcutaneous
administration. Endometrial tissue is overactive in absorbing progesterone. Benefits of
progesterone releasing IUD include
 improved functioning
 decreased menstrual flow
 dysmenorrhea.

25. Progesterone releasing IUD
– On the other hand, the disadvantage includes
 the need to be changed every year
 bleeding during menstruation
 ectopic pregnancy.
Progesterone-containing contraceptive IUD can include the following anti-fertility side effects:
 They Reduce The Transport Of Sperm From The Cervix To The Oviduct By Increasing The Size Of The
Cervical Mucus.
 Steroid-releasing Devices Induce Progesterone Changes That Lead To Endometrial Proliferation And
Inhibit Ova Development.
 Endometrial Lining Does Not Favour Blastocyst Implantation. This Is Associated With A Limited
Formulation Caused By Progesterone.
 The Effect Of The Estrogen-progesterone System Is Related To The Presence Of Electrical
Membrane Energy That Prevents Ovum-endometrium Contact Before Implantation.

26. – Progestasert
– It is a T-shaped novel Progestasert controlled releasing IUD made of ethylene and
vinyl acetate copolymer containing titanium dioxide.
– The IUD was approved by USFDA in 1975 for 12-month contraceptive use. It
contains a hollow core in the middle.
– It is 0.25mm thick.
– The progesterone is released by diffusion through a rate-limiting membrane.
– In this IUD 38 mg of progesterone reservoir and barium sulfate are present in
silicone fluid in the vertical stem along with dispersed barium sulfate in silicon fluid.
– Progesterone is released at a rate of 65 micrograms per day for 1 year. Deficiency
includes ectopic pregnancy and chances of PID.
– The progesterone is released at the rate of 1.8/100 for parous and 2.5/100 for
nulliparous women.
– It does not inhibit ovulation but interferes with implantation in the endometrium
by causing the thickening of cervical mucus

27. Levonorgestrel releasing IUD
– These contain levonorgestrel-releasing devices.
– It is an intrauterine system with sleeves containing levonorgestrel 52 mg
around its base.
– It contains a polyethylene stem coated with a matrix Silastin: LNG (2: 1).
– Withdrawal of 20 mcg/day and duration of at least 5 years.
– Immediate release and then at a dose of 60% drug reduction reduced to 16mcg
/ day.
– It also suppresses the endometrium and ovulation. Also, unlike other IUDs, it
can reduce the risk of (PID).

28. Levonorgestrel releasing IUD
– These IUDs prevent pregnancy by damaging or killing the sperm and making the
mucus thicker and sticky, so the sperm cannot enter the uterus.
– It also keeps the endometrium from growing too much, making the membrane
a poor place for the fertilized egg to grow and develop.
– It can reduce irregular menstrual bleeding and cramping.

29. Levonorgestrel releasing IUD
– Levonorgestrel releasing IUDs (Mirena, Liletta)
– It is made of T-shaped polyethylene radiopaque frame measuring 32mm x 32mm.
– A hormone cylinder is made of a combination of 52 mg levonorgestrel and silicon
(polydimethylsiloxane) which regulates membrane drug release.
– LNG is released in the first year at a rate of 20 ug / d for 5 years. Example Mirena, Liletta,
levosart.
– The LNG-IUS 20 (Mirena) is approved in the US for 5 years of use for contraception and the
treatment of heavy menstrual bleeding.
– In more than 100 countries, this IUD is also approved as a source of progestogen to prevent
endometrial proliferation with the use of postmenopausal estrogen therapy.
– The applicator used to place this IUS utilizes a straightforward single-handed placement
procedure.
– The cost of this IUD generally tends to be higher than the newer version

30. Levonorgestrel releasing IUD
– Levonorgestrel releasing IUDs e.g. Skyla/jaydess)
– It is small in vertical and horizontal dimensions. The arms are 28 mm long and the shaft is 30
mm long. The T-shaped frame is made of polyethylene. Only 13.5 mg of LNG is circulating in
the reservoir. Jaydess popularly known as Skyla in the United States emits an average of 8 ug /
d over one year with a minimum release of 13.5 mg LNG.
– LNG-IUS 8 is three years old, a small tool that releases low levels of hormones and is stored
using a small diameter tube. Low hormone levels lead to lower amenorrhea, which can attract
women who do not want an increase in blood loss (such as copper IUD) but do not want
amenorrhea (LNG-IUS 20).
– LNG-IUS 20 (Lettae / Levosart) is very similar to Mirena but is currently only allowed for three
years. However, clinical trials continue to study its potential for use for up to 7 years. In the
European Union, but not in the US, the IUS has also approved treatment for severe menstrual
bleeding. The placement of the IUS involves a complex one-handed process

31. Levonorgestrel releasing IUD
– Disadvantages of LNG IUD
 It can cause non-cancerous or benign growth called ovarian cysts
 It can cause hormonal side effects, such as chest tightness, breast tenderness,
mood swings, headaches, nausea, acne, etc. When side effects occur, they
usually subside after the first few months.
The contradiction of LNG IUDs include ectopic pregnancy, puerperal sepsis or
miscarriage, miscarriage (stillbirth), unexplained bleeding of the vagina, genital
injury, tuberculosis, Pelvic Inflammatory Disease (PID)

32. Non-Medicated IUDs
– IUDs contain a bioactive component.It made of non-abrasive materials such as
stainless steel or plastic.
– The stainless steel (SSR) ring is a flexible ring that is to be inserted through the cervix.
– A plastic-like Lippes loop, which can be inserted into the cervix into a cannula takes a
trapezoidal shape into the uterus. It is less effective than a copper or hormonal IUD
– They use their contraceptive action by producing a sterile inflammatory response in
the endometrium by its mechanical interaction
– The mechanism involves a local body reaction that causes the uterus to become
hostile to both sperm and prevents the implantation of the embryo. These IUDs have
a higher rate of contraception after pregnancy compared to a copper or hormonal
IUD.

33. APPLICATION
– IUDs that release copper or levonorgestrel are extremely effective contraceptives.
The LNG-IUS also reduces menorrhagia and dysmenorrhoea(1)
– The LNG-IUS is a proven alternative to hysterectomy and endometrial ablation.
Many surgical procedures are still performed without first evaluating the LNG-IUS or
other medical treatments. Not only is the LNG-IUS highly effective in reducing MBL,
but it is also well-tolerated, has a high user satisfaction rate, and is cost-effective.
– Intrauterine contraception provides contraception that is just as effective as, and
arguably safer than, female sterilization.
– Some studies have found that women with copper IUDs tend to have a lower risk of
endometrial cancer

34. APPLICATION
– It can be used as an adjunctive treatment modality for intra-uterine adhesion.IUD can be
beneficial for patients with intrauterine adhesions or Asherman’s syndrome especially when
combined with other ancillary treatments
– IUDs include treatment of anaemia, dysmenorrhea, and pelvic pain-associated endometriosis
and offer endometrial protection against hormonal replacement.
– Non-hormonal IUDs are considered safe during breastfeeding
– Many providers recommend the progestin IUD for women who suffer from extremely heavy,
prolonged, or painful menstruation because it tends to lighten their periods or even suppress
them altogether
– The copper IUD is considered a category 3 choice for initiation in women with solid organ
transplants, systemic lupus erythematosus with severe thrombocytopenia, gestational
trophoblastic disease, and pelvic tuberculosis
– The copper IUD may be the best choice for women with these serious health problems,
because it offers excellent pregnancy protection without exposing users to exogenous
hormones and because the risk of pelvic infection is so low

35. REFERENCES
 Sandra Klein KT. Vaginal and Intrauterine Delivery Systems. n Vitro Drug Release Testing of Special Dosage Forms. 2020;(1): 177-209.
 Vancha H. Intrauterine and Intravaginal Drug Delivery systems: an overview. Journal of Emerging Technologies and Innovative Research
(JETIR). 2018 December; 5(12): 182-192.
 Margret chandira DBcBj. ON INTRA-UTERINE DRUG DELIVERY SYSTEM-A REVIEW. ;: 1-22.
 Anita L Nelson NM. New developments in intrauterine device use: focus on the US. Open Access Journal of Contraception. 2016
September;(7): 127-141.
 Debjit Bhowmik CDKTKPSK. Recent advances in Intrauterine Drug Delivery System. Annals of Biological Research, Scholar Research
Library. 2010; 1(1): 70-75.
 Group TECW. Intrauterine devices and intrauterine systems. Oxford University. 2008; 14(3 pp.): 197-208.

36. REFERENCES
 Group TECW. Intrauterine devices and intrauterine systems. Oxford University. 2008; 14(3 pp.): 197-208.
 Natalie S Whaley AE. Intrauterine contraception. Women's Health. 2015;: 1-9.
 Susan Rose ACCMP. Mirena® (Levonorgestrel intrauterine system): A successful novel drug delivery. ELSEVIER. 2009;: 808-812.
 Y.W.Chien. Novel Drug Delivery System. In Decker M, editor. Novel Drug Delivery System. 2nd ed. p. 585-630.
 N.K.Jain. Advances in Controlled and novel drug delivery. In N.K.Jain. Advances in Controlled and novel drug delivery. p. 112-123.
 Brahmankar D M JSB. Biopharmaceutics and Pharmacokinetics A Treatise. In Brahmankar D M JSB. Biopharmaceutics and
Pharmacokinetics A Treatise.: Vallabh Prakashan; 2015. p. 509-511.