This document discusses intrauterine devices (IUDs) as a form of contraception. It begins with an introduction to contraception and the anatomy of the uterus. It then discusses the history and development of IUDs, including early non-medicated IUDs made of materials like plastic and copper-bearing IUDs that enhance effectiveness. The document outlines the types of modern IUDs, including copper IUDs and hormone-releasing IUDs. It compares the efficacy of medicated versus non-medicated IUDs and discusses new developments in long-acting IUD designs.

2.  Introduction
 Contraception
 Need of Contraceptives
 Anatomy of uterus
 Types of contraception
 Introduction of IUDs
 Intra Uterine Devices-
 Types of IUDs
 Advantages of IUDs
 Disadvantages of IUDs
 Design of IUDs
 Development of medicated IUDs
 Copper bearing IUDs
 Hormone releasing IUDs
 Comparative efficacy of medicated & non-medicated IUDs
 New development
 References

3. INTRODUCTION
CONTRACEPTION:
• Contra-opposite/ prevent
• Ception- conception (union of male & female
gamates to reproduce new ones)
It is the method or technique or process
which results into temporary or permanent loss
of capability to reproduce or conceive a young
one.

4.  1975- United state
 From approximately 27 million couples of child baring
age 76.3% expressed desire to prevent conception
either temporarily or Permanently.
Method of
Contraception
% of those
served
Oral contraceptive pills 26.3
Condom or Diaphragm 10.0
Intrauterine devices 6.4
Foam 2.6
Rhythm 2.2
Other 28.8

5. Pear shaped, thick-walled
muscular organ suspended in the
anterior wall of pelvic cavity.
Shape: triangular, flattened
antero-posteriorly.
Dimensions: (in normal state)
Length- 3 inches
Width- 2 inches
Parts-
 Fundus
Body (Uterine Cavity, Isthmus)
Cervix (Cervical canal, Internal Os,
External Os)
Openings-
Superior- fallopian tubes
Inferior- Vagina (mouth of
Uterus)

6.  Endometrium – inner coat of uterine wall made up of
simple columnar epithelium, areolar connective tissue &
endometrial glands.
 Stratum Functionalis- innermost, sloughed off during
menstruation
 Stratum Basalis- permanent, gives new s. functionalis.
 Myometrium – Thick, muscular middle layer made up of
3 layers of smooth muscles (Middle thick circular &
other two longitudinal)
 Peritoneum – External surface of uterus which attaches
uterus to pelvic cavity by ligaments

7.  During reproductive ages nonpregnant woman
exihibit cyclic changes in ovaries & uterus, called
as Menstrual cycle.
 Typically of 28 days & divided into 4 phases-
 Menstrual Phase (5 days)
 Pre-ovulatory phase / Follicular phase (6-13 days)
 Ovulatory phase (on 14th day)
 Post-ovulatory phase / Leutial phase (14-28 days)

9.  Menstrual phase- (5 days)
 Decrease in levels of estrogen & progesterone
 Stimulates release of prostaglandins
 Produce arteriole constriction, decrease blood supply to s.
functionalis
 Cells starts to die & s. functionalis sloughed off.
 Bleeding takes place for about 5 days.
 Follicular phase- ( up to 13th day)
 Estradiole is secreted from ovaries by secondary follicle
 Secondary follicle is converted in graffian follicle.
 Estrogen restores blood supply to endometrium & stimulates
formation of s. functionalis from s. basalis.
 S. functionalis starts to grow and become 3-4 mm thick.
 Endometrial glands increase in length & tortuosity.

10.  Ovulation-( on 14th day)
 Release of oocyte outside of ovaries into fallopian tube.
 Takes place at the day of 14 of M.C. under the influence of
Leutinizing hormone (LH) & Gonadotropin releasing hormone
(GnRH)
 Released oocyte remain viable for 2 days.
 Leutial phase-(15-28 day)
 In ovary graffian follicle collapse to form corpus luteum. It
release progesterone & estrogen.
 In uterus, these hormones promote growth, thickning & coiling
of endometrium. Glycogen is secreted by glands.
 Fertilization- changes remain constant
 No fertilization- corpus luteum disappear, decrease in level of
estrogen & progesterone. Menstruation occurs.

11.  DEFINITION
IUD’s are medicated devices intended to release a small quantity of drug
into uterus in a sustained manner over prolonged period of time.
 3 most popular methods of contraception:
 Oral contraceptive pills
 Condoms or diaphragms
 Intrauterine device
Methods of
contraception
Pregnancies Births Deaths MBR (Mortality
Benefit Ratio)
P M Total
None 60,000 50,000 12 0.0 12.0 -
Condom or diaphragm 13,000 10,833 2.5 00 2.5 0.664
Oral pills 100 83 0.0 3.0 3.0 0.060
IUDs 2190 1825 0.44 0.3 0.74 0.015
MBR-Deaths per 1000 births averted as related to pregnancy (P) Or Method (M)
1,00,000 fertile women data with each method

12.  NON MEDICATED:
 Ring shaped iud’s made of stainless steel which haven used by 50
millions women in china .
 Plastic IUDS :
Fabricated from polyethylene or polypropylene which are sold in
Asia, south Africa ,south America.
 Lippes loop iud & Saf -T-coil is still available commercially in US.
 MEDICATED:
 Copper bearing IUD E.g. cu 7, CuT-380
 Progesterone releasing IUDS e.g., Progestasert

13.  1920- First generation IUD’s
 Constructed from silkworm gut & flexible metal wire
Eg. Grafenberg star & Ota ring
 Decline in popularity-
 Difficulty in insertion
 Need for frequent removal- pain & bleeding
 Other serious complications

14.  Then-
 Several Plastic based IUD’s of varying sizes & shapes
were prepared using inert biocompatible polymers
like-
 Polyethylene
 Polypropylene
 Ethylene-vinyl acetate copolymers
 Silicon Elastomer

15.  Modern Era- development of
 Margulies- Plastic spirals
 Lippes- Loop
 Dalkon shield IUD
 Efficacy of these IUD’s was proportional to their
surface area that is in direct contact with
endometrium.
 Larger IUD’s were more effective but expulsion
rate is high as these produce-
 Endometrial Compression
 Myocardial Distention
 Uterine cramps
 Bleeding

16.  Tatum & Zipper (1967) develop T- Shaped polyethylene
device.
 This significantly reduce side effects
 Pregnancy rate become to 18%
 Good Uterine tolerance
 Non-medicated IUD’s-
 Act through mechanical contact with endometrium
 Size is important factor
 Large size produce irritation & other side effects
 High expulsion rate
 No improvement in contraception efficacy.
 Starting of new era-
 As this devices acts as carrier of choice for intrauterine
delivery of contraceptive agents.

17.  1969
 Zipper et. al. reported- copper attached to an
IUD markedly enhanced the effectiveness.
 T-shaped polyethylene device wound with
30 mm2 copper wire (Cu-T-30)
 The pregnancy rate was reduced to 5% from
18%.
 Additional clinical evaluations with larger
surface area of copper wire
 200 mm2 – found maximum contraceptive
efficiency.

18. 18
 The device is made of T
shaped polyethylene plastic.
 This device uses copper wire
wound to the stem of T.
 Grades as per the surface
area of wire
• Cu-T-30,
• Cu-T-200,
• Cu-T-380.

19.  Cytotoxic, Spermatocidal & spermato-depressive action
 Competitive inhibitor of steroid-receptor interaction.
Eg. Cupric ions –Potent inhibitor
 17 estradiol & Progesterone binding to their receptors.
 Progesterone receptors were more susceptible.
 Progestational proliferation severely inhibited.
 Cu taken up by endometrial epithelium & stromata.
 Cu conc. in uterine cytoplasm –1.4 x 10-6 M
 Little effect on sperm mobility.

20.  Continuous release by ionization & chelation process.
 Diameter of wire was reduce with time by corrosion
& flacking of metal
 Cu-7 284 deliver Cu at a rate of following expression-
Dosage (mg)=0.3 * month + 3.79
 Release 9.87 µg/day
 Linear relationship between cumulative copper
release with the duration
 Reduction in copper release due to formation of-
 Corrosion layer- of protein
 Encrustation layer- of calcium (impermeable)

21. Clinical effectiveness for 3- years use of Cu-T-200
Event Year 1 Year 2 Year 3
Pregnancies 2.6 2.5 3.6
Expulsions 7.3 2.3 2.5
Removals
Bleeding/ pain
other medical reasons
Planning pregnancy
Other medical reasons
8.7
2.7
1.9
2.3
7.3
2.4
4.4
3.4
5.2
2.0
7.0
7.9
Termination rates 25.5 22.3 28.3
Continuation rates 74.5 77.7 71.7
*Events per 100 women

22.  Mfg by G.D. Searle & Co.
 First device approved by US- FDA for 3 yrs of
use.
 Polypropylene plastic device shaped like 7
 89 mg copper wire around vertical limb with
surface area of 200 sq. mm
 Release 9.87µg/day for 40 months
 Smaller volume (0.09 cm3) than Cu-T (0.16 cm3)
- easily inserted in nulliparous women.
 No need of cervical dilation
 Removal is painless.

24.  Efficacy improved when copper wire is located on the
transverse arm as in close contact with upper portion of
uterine cavity.
 Cu-T-380A (US approval -1980)
 Two collars of Cu on transverse arm
 Each collar provides additional surface are of 30 sq. mm.
 Cu-T-200C
 Seven copper sleeves of Copper on both arms
 Efficious same as Cu-T-380A
 Retain physical integrity for 15-20 yrs.
 Long acting- beneficial to population in which medical
care not readily available.

25.  Multiload Cu IUD: MLCu-250
 Combination of Cu-T & Dalkon Shield without central plastic
membrane.
 Blunt apex of device fits in to vault of uterine cavity without
penetrating endometrial walls
 Two teeth-studded side arms adapt to the contours of the uterine
cavity
 During uterine contraction Fundus presses against upper edge of
IUD, results in bending of arms.
 Pregnancy rate- 0.3% only
 Expulsion- 1% only
 Other Devices-
 MLCu-250,
 MLCu-325
 MLCu-250 mini

26.  Use of hormone in IUD- initiated by Doyle & Clewe
 Then Croxatto et al showed that a progestin released
at a controlled rate from a silicone capsule inserted in
rabbit uterine cavity, prevent implantation.
 1970- Scommegna & coworkers affix progesterone
containing silicone capsules to modified Lippes loop.
Granted US-patent.
 Early models had high expulsion rates or side effects.
 T-shaped progesterone releasing IUD were
developed, improvement in efficacy.
 Release rate of 65 µg/day was found to produce
contraception & selected as final design of IUD.

27.  Secretion of secretary phase is hormonally controlled
 Optimum amt. of estrogen & progesterone required for
proper development.
 Implantation of blastocyst takes place on secretary
endometrium.
 Decidual reaction- after implantation
 Stromal cells enlarge & grow as polyhedral cells rich in
glycogen & lipids. These changes takes place in presence
of implanted blastocysts.
 Once decidual reaction occurred, implantation of
blastocyst cannot takes place again.
 Endometrial hyper-maturation is unfavorable for
implantation.
 Maturation of endometrium is associated with decidual
formation which is induced by Progesterone.

28.  Dependant upon daily
dose of progesterone
released
Dose release per day (µg) Pregnancy rate
(%)
No Progesterone 22
10 5.2
25 2.7
65 1.1
120 0.6
Life table analysis of the clinical effectiveness of Progestasert
Events Parous women Nulliparous
women
Pregnancy 1.9 2.5
Expulsions 3.1 7.5
Removals 12.3 16.4
Continuation rate 79.1 70.9

29.  Membrane Controlled Reservoir type D.D.Ds-
Polymeric membrane encapsulates the drug &
also controls the release.
 Two types
 Single Component System
 Multiple Component System
Cont.

30.  Single Component System
 Drug in solid form encapsulated in capsule of
biocompatible polymeric material
 Polymer- Silicone elastomer / Polyethylene
 E.g. Scommegna’s silicone-based IUD
 Drug release- zero order kinetics
 Silicone elastomer widely used previously as
polymer- do not posses required tensile
strength or elastic modulus.
 To overcome drawbacks- copolymers of
Poly(dimethylsiloxone) with polycarbonate or
polyurethane were prepared.
Cont.

31.  Multi component System-
 Encapsulation of liquid medium saturated with
excess of drug in rate controlling polymeric
membrane.
 E. g. Progestasert (Alza Corp.)
 Membrane- Ethylene vinyl acetate copolymer
 38 mg of Progesterone suspended in silicone oil
 Release at constant rate of 65 µg/day
 Zero order release rate till drug solution become
unsaturated
 60% of loading dose in reservoir compartment
depleted during first year.
 Useful life is 1 yr.

32.  Polymer-matrix Diffusion-Controlled D.D.Ds-
Homogenously dispersing drug particles in a cross
linked polymeric matrix
 Two types
 Retrievable Matrix Device
 Biodegradable Matrix Device

33.  Retrievable Matrix Device-
 Retrieved or removed after termination of
treatment
 Preparation-
1) Mix drug powder with a semisolid silicone
elastomer  vulcanization at room / low temp.
2) Mix drug powder with low density polyethylene
particles  Melt & extrude
 Drug release is linearly proportional to square root
of time
Cont.

34.  Biodegradable matrix device:
 No need of retrieving at the termination of treatment.
 Preparation –
Dissolve drug + Biodegradable polymer e.g.
Poly(lactic acid)  in common organic solvent 
Melt pressing at elevated temp. after flashing off
solvent
 Drug release is combination of polymer hydrolysis &
drug diffusion

35.  Sandwich-type D.D.D.
 Hybrid of polymer membrane permeation with polymer
matrix diffusion
 Thin rate controlling membrane encapsulates a high
permeable drug dispersing matrix.
 Release rate can be improved by coating porous support
with silicone elastomer.
 E.g. Nova-T (Leiras Pharmaceuticals, Finland)
 Drug Levonorgesterel (more potent progesterone analog)
 T shaped polyethylene support by a sandwich type silicone
based drug reservoir
 Daily release – 20 µg
 Lifetime- more than 5 yrs.

36.  Estriole Releasing IUD’s
 Synthesis of estradiole dependant
uterine RNA is essential for
implantation
 Estriole binds with uterine
receptors & compete with
estradiole. But incapable of
inducing uterine growth.
 It interfere with synthesis of
estradiole induced uterine RNA,
preventing implantation.
 Release rate of 1.25 µg/day
effectively inhibits development &
implantation of blastocyst.

37.  Use of Cu -7 group was declined due to the problem
of excessive bleeding .
 Irregular bleeding was higher in Cu – 7 group
(13.4%) than in progestasert group (7.5%).
 But progestasert has a limited life span of one year
which is disadvantageous as compared to three
year users life of Cu -7.
Cont.

38. Changes in enzymatic activity-
 Copper bearing IUD produce significant variations in
secretary phase of the endometrium with two fold
increase in total enzyme activity.
 Progesterone releasing IUD induced no (or only small )
change in activity of lysosomal enzymes and increased
the stability of lysosomal membrane during secretary
phase.
 The changes in activities and sub cellular distribution
of lysosomal enzymes induced by non medicated
placebo IUD were found to be quantitatively small and
of limited biological significance .
Cont.

39. Changes in endometrium-
 The plain and copper bearing spring coil IUDs the cyclic
patterns of endometrium was preserved .
 Progesterone releasing IUDs produce the histological
changes that made endometrium unsuitable for
implantation .
 Mestranol releasing device produces proliferative or
hyperplastic changes in both glandular & stromal cells
with prevention of secreatory changes in endometrium
which become unreceptive to ova
Cont.

40. Changes in menstrual bleeding-
 Insertion of copper bearing IUDs has resulted in
increased in menstrual blood loss and decreased in Hb
compared to pre insertion cycle
 Insertion of progesterone releasing IUDs yielded either
no change or reduction in menstrual blood loss & no
significant variation in Hb conc.

41.  The copper IUD prevents ectopic pregnancies.
 This contraceptive is very cost effective
(inexpensive) over time.
 Use of an IUD is convenient, safe & private.
 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.

42.  There may be cramping, pain after insertion.
 The number of bleeding days is slightly higher than
normal
 Somewhat increased menstrual cramping.
 If bleeding pattern is bothersome, contact the doctor.
 The IUD provides no protection against sexually
transmitted infections.
 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 or physician’s
assistant.

43.  Y.W. Chien. Novel Drug Delivery
System, 2nd edition, Marcel
Decker , page no.- 585-630
 Advanced in controlled & novel
drug delivery-N.K.Jain.
 Remington-the science & practice
of pharmacy vol.1&2.
 www.google.com.