Intrauterine Drug Delivery System 735k2j

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Introduction Contraception  Anatomy of uterus  Types of contraception 

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Introduction of IUDs Intra Uterine DevicesTypes of IUDs  Advantages of IUDs  Disadvantages of IUDs  Design of IUDs 

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Development of medicated IUDs Copper bearing IUDs  Hormone releasing IUDs 

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Comparative efficacy of medicated & non-medicated IUDs Evaluation of IUDs New development References

INTRODUCTION CONTRACEPTION: • •

Contra-opposite/ prevent Ception- conception (union of male & female gamate 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.

 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

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   

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: Oral contraceptive pills Condoms or diaphragms Intrauterine device Methods of contraception

Pregnancies

Births

MBR deaths/ l000 births

Deaths 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

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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.

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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, 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

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

 a) b)

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 configuration The T shape conforms well to uterine cavity, minimizing the distortion of myometrium Displacement & rotation of the T-shaped IUD inside the endometrial cavity are resisted by the three points of between device & the endometrial wall.

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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 .

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

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

 DEVELOPMENT

OF MEDICATED IUD’s-

 E.g..

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

Shape of uterine cavity:

Myometrial fibers contract

T shaped uterine cavity

Utreine wall thickens and shortens

Contraction increases

Smaller endometrial cavity

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Feature: 



Long term treatment of antifertility agents.

COPPER 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

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Spermatocidal & spermatodepressive action

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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

Pregnancy rate

 Effectiveness.

Surface area

Uterus

Pregnancy rate

Uterine cavity

Thread for insertion or removal of device

Diagram of Cu-T

Cu – T

Cu – 7

Copper wine around plastic T

Treatment (Months)

 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.

Pregnancy rate(%rate/ woman)

Polyethylene

Release rate (ug/day)

Ethylene vinyl acetate copolymer

38 mg of progesterone microcrystals (and barium sulfate)suspended in silicone oil

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

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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

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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 with silicone elastomer.

 Eg.of

STDD-nova –T

Antifibrinolytic acid,trenexamic acid.

IUD’s-aminocaproic

 Polymeric 

Single component system:



membrane encapsulates with drug

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.



a)

b)

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%). The menstrual blood loss in progestasert s was reduced compared to pre insertion blood loss The progestasert has a limited life span of one year which is disadvantageous as compared to three year s life of Cu -7.



a)

b)

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 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. 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 .



a)

b)

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

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

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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-T220C device is projected to retain its physical integrity for 15-20 years of continuous intrauterine istration 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.- 585630

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Advanced in controlled & novel drug delivery-N.K.Jain.



Remington-the science & practice of pharmacy vol.1&2.

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