Introduction Contraception 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

Evaluation of IUDs New development References

INTRODUCTIONINTRODUCTION

CONTRACEPTION:CONTRACEPTION:• Contra-opposite/ preventContra-opposite/ prevent• Ception- conception Ception- conception (union of male & female gamate to reproduce new ones)(union of male & female gamate to reproduce new ones)

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

Wall of uterus – 3 layers Endometrium – inner coat of uterine

wall mucous membrane. Epithelial lining and connective tissue.

Myometrium – Thick, Muscular middle layer connective tissue.

Peritoneum – External surface of uterus which attaches to pelvic cavity by ligaments

DEFINITIONDEFINITION 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: Oral contraceptive pills Condoms or diaphragms Intrauterine device

Methods of Methods of contraceptioncontraception

PregnanciesPregnancies BirthsBirths DeathsDeaths MBR deaths/ MBR deaths/ l000 birthsl000 births

PP MM TotalTotal

None None 60,00060,000 50,00050,000 1212 0.00.0 12.012.0 --

Condom or Condom or diaphragm diaphragm

13,00013,000 10,83310,833 2.52.5 0000 2.52.5 0.6640.664

Oral pills Oral pills 100100 8383 0.00.0 3.03.0 3.03.0 0.0600.060

IUDs IUDs 21902190 18251825 0.440.44 0.30.3 0.740.74 0.0150.015

Two types of IUDs

1) Medicated :

A) copper bearing IUD E.g. cu 7

B) Progesterone releasing IUDS e.g., Progestasert

2)Non medicated:

A) Ring shaped iuds made of stainless steel which haven used by 50 millions china .

B) Plastic IUDS :

Fabricated from polyethylene or polypropylene which are sold in Asia, south Africa ,south America.

C) Lippes loop iud & Saf -T-coil is still available commercially in Us .

Side effects: Pains, bleeding,difficulty in inserction and removal,

cramps, expulsion of IUD.

•Copper T IUD (ParaGard) and Levonorgestetrel IUD (Mirena) are the two most effective reversible methods of birth control.•Copper T 380 A IUD (ParaGard) is effective for at least 12 years.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.

There may be cramping, pain or spotting after insertion.

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 very small percentage of women are allergic to copper.• A small percentage of IUDs may be expelled by a woman’s body within the first few months due to an improper fit.

Design of IUDs

As the myometrial fibers contracts, uterine wall thickens & shortens & in response the endometrial cavity become smaller in all directions.

As the contraction increases lateral wall of cavity approximate one another & the cavity assumes the shape of letter ‘T’.

Two distinct features of the T configurationa) The T shape conforms well to uterine

cavity, minimizing the distortion of myometrium

b) Displacement & rotation of the T-shaped IUD inside the endometrial cavity are resisted by the three points of contact between device & the endometrial wall.

When the uterine cavity is empty , the endometrial surface are separated from one another only by a thin layer of mucus and other secretion fluids of the endometrial glands and tuber epithelium .

The volume and shape of the uterine cavity depend on contractile state of myometrium normally reflecting the summation of myometrial forces .

The average dimension of the endometrial cavity at several levels ha s been computed .

DEVELOPMENT OF MEDICATED IUD’s-DEVELOPMENT OF MEDICATED IUD’s-

E.g.. contraceptive metals such as Cu, Progestin, Smaller T Shaped device.

Shape of uterine cavity:

Utreine wall Utreine wall thickens and thickens and shortensshortens

Smaller Smaller endometrial endometrial cavitycavity

T shaped uterineT shaped uterinecavitycavity

Contraction Contraction increasesincreases

Myometrial fibers contractMyometrial fibers contract

Feature: Long term treatment of antifertility agents.

COPPER BEARING IUD’sCOPPER BEARING IUD’s (9.87 µg/day) Cytotoxic

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

Spermatocidal & spermatodepressive

action

Competitive inhibitor of steroid-receptor

interaction.

Eg.Cupric ions –Potent inhibitor of

binding 17 estradiol to human

endometrial cytosol.

Cu conc. in cytoplasm –1.4 x 10-6 M

Anti-fertility activity-surface area

Effectiveness.

Pre

gn

an

cy

ra

te

Surface area

Diagram of Cu-T Diagram of Cu-T

Copper wine around plastic T

Thread for insertion or removal of device

Uterine cavity

Uterus

Pre

gn

ancy

rat

e

Treatment (Months)

Cu – T

Cu – 7

OBJECTIVES

Enhance uterine retension

Show slowly releasing steroids

e.g. Melengestrol acetate.

Formulation:

Suspension of Progesterone microcrystal Silicon medial

fluid Ethylene- Vinyl acetate copolymer (EVA)

Release rate-65 g/ day for one year.

Pre

gn

an

cy

rate

(%ra

te/

wo

ma

n)

Release rate (ug/day)

PolyethylenePolyethylene

Ethylene vinyl Ethylene vinyl

acetate copolymeracetate copolymer

38 mg of progesterone microcrystals (and barium38 mg of progesterone microcrystals (and barium

sulfate)suspended in silicone oilsulfate)suspended in silicone oil

Polymer-matrix Diffusion-Controlled D.D.Ds-

Biodegradable matrix device:

Eliminate the need of retrieving.

Prepared by –Dissolve drug + Biodegradable polymer (Polylactic

acid) Common organic solvent Melt pressing at elevated

temp after Flashing off solvent

Sandwich–type drug delivery device:

Hybrid of polymer membrane permeation.

Thin rate controlling membrane encapsulates a high permeable

drug dispersing matrix.

Release rate Coating porous support with silicone elastomer.

Eg.of STDD-nova –T

Antifibrinolytic IUD’s-aminocaproic acid,trenexamic acid.

Polymeric membrane encapsulates with drug Single component system:-

Contraceptive agent encapsulate into capsule of biocompatible polymeric materials (Silicon elastomers & Polyethylene).

Multi component system:- Encapsulating liquid medium with excess drug particles

in polymer. e.g. Progestasert.

The removal in Cu -7 group were due to the problem of excessive bleeding .Irregular bleeding was higher in Cu – 7 group (13.4%) than in progestasert grout (7.5%).

a) The menstrual blood loss in progestasert users was reduced compared to pre insertion blood loss

b) The progestasert has a limited life span of one year which is disadvantageous as compared to three year users life of Cu -7.

The insertion of copper bearing IUD yielded some significant variations primarily in secreatory phase of the endometrium with total enzyme activity increased at least twice

a) The progesterone releasing IUD induced no ( or only small ) change in activity of lysosomal enzymes and increased the stability of lysosomal membrane during secreatory phase.

b) 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 .

The plain and copper bearing spring called IUDs the cyclic patterns of endometrium only significant change found in leukocytic infiltration of endometrium which was more intense with the copper bearing device .

a) Progesterone releasing IUDs produce the histological changes that made endometrium unsuitable for implantation .

b) Mestranol releasing device produced advanced proliferative or even hyperplastic changes in both glandular ad stromal cells from week first to week fifth with prevention of secreatory changes in endometrium which become unreceptive to ova

Insertion of inert or copper bearing IUDs has resulted in increased in menstrual blood loss and decreased in hemoglobin compared to pre insertion cycle

insertion of progesterone releasing IUDs yielded either no change or reduction I menstrual blood loss and no significant variations in hemoglobin .conc

Copper-bearing intrauterine device:• In the evolution of Cu-T-220 with seven

cooper sleeves(~30mm2each)enveloping both transverse arms & vertical stem.

• The analyses of copper content lost from the sleeves after 2 years of in utero use the Cu-T-220C device is projected to retain its physical integrity for 15-20 years of continuous intrauterine administration of contraceptive copper. this type of long acting contraceptive device will be particularly beneficial to populations in which medical care is not readily available.

1. Hormone releasing IUDS are evaluated by attachment of steroid containing silicon capsules in various carriers of different shapes or sizes .

2. In the evaluation of T- shaped progesterone releasing IUD in which drug containing silicon capsules forms an integral part of vertical limb of polyethylene T device.

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.

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