W12 Dosage forms of contraceptive drugs (AM)

Question 1

Combined oral contraceptive

Answer 1

Combined oral contraceptive (COC): oestrogen & progestogen

• It’s not a pill
• Pill = active ingredient is mixed with
  other (adhesive) substances to create
  small oral dosage forms
• COC and POP are simply tablets
• Used calendar packs to help improve
  compliance
• 28-day packs available
• Contain 7 placebo or dummy tablets

Question 2

Emergency hormonal contraception:
What are examples?

Answer 2

• PC4 launched as POM in the UK in 1984
• Progestogen-only EHC (Levonelle®) available as POM in 2000
• Levonelle® switched to P-status on 1 January 2001
• ellaOne® available as POM in 2009 (OTC since 2015)
• All are tablet dosage forms

(ulipristal acetate, levonorgestrel, ethinyloestradiol and norgestrel)

Question 3

Transdermal contraception

Answer 3

• Transdermal contraceptive patch (Evra®) launched in 2002
• Patch is left in place for 7 days (buttock, abdomen, upper outer arm or upper torso)
• 3 patches used for 21 days and then a 7-day patch-free period
• Each transdermal patch releases an average of 203 micrograms of norelgestromin and 33.9 micrograms of ethinyl estradiol per 24
  hours

Hormones are incorporated in a separate polymeric matrix which may be in direct contact with the skin or drug may also have to permeate adhesive layer

Question 4

Intrauterine device (IUD):
What is the structure?
How long does it provide protection for?

Answer 4

• An IUD is a long-acting reversible contraceptive (LARC)
• T-shaped (low density) polyethylene and copper device
• IUD supplied with a (large) insertion device
• Inserted into the uterus by a GP or practice nurse and provides protection from
  pregnancy for up to 10 years

Question 5

Intrauterine device (IUD)

Answer 5

• Two threads enable the user to check the IUD is remains in place
• IUD supplied sterile in the primary pack along with the insertion device
• Both arms are coated with a copper shoulder and the main body is wrapped with copper wire

Device typically impregnated with barium sulphate (which is visible on an X-Ray)

Question 6

Intrauterine device (IUD):
What are the contraceptive effects of the copper ion release?

Answer 6

• Best evidence suggests IUDs should have a copper surface area of
  300 mm2 or more for best contraceptive effectiveness
• Copper ion release from the IUD has several contraceptive effects:
  − It has spermicidal properties
  − Causes localised uterine inflammation – unsuitable for fertilisation
  − Alters the cervical mucus → (1) more difficult for sperm to reach an egg
  and survive; (2) stops fertilised egg from implantation
• A global copper shortage is currently contributing to IUD supply
  issues
• Global issues: reduced mining in Peru/Chile, “reopening” of China pushing prices higher, energy transition and electric vehicles

Question 7

Intrauterine system (IUS)

Answer 7

• The term intrauterine system (IUS) is reserved for IUDs that contain hormones (typically a progestogen)
• IUDs are “devices” whereas IUS are POMs
• Brands of IUS used in the UK on the NHS:
  − Mirena® - levonorgestrel 20 micrograms/24 hours
  − Levosert® - levonorgestrel 20 micrograms/24 hours
  − Jaydess® - levonorgestrel 6 micrograms/
  24 hours (average over 3 years)
• How is this controlled release obtained?
• We use a polymer that will release the drug over time

Question 8

Intrauterine system (IUS)

Answer 8

• We use a biostable polymer and retrieve the delivery device (IUS) after 5 years
• Mirena®, Levosert®, and Jaydess® brands all employ polydimethylsiloxane (PDMS) or “silicone”
• PDMS is crosslinked and stable in aqueous conditions
• Drug controlled release based on diffusion through voids within the polymer
• Presence of covalent crosslinks slows the permeation of the drug from the PDMS reservoir
• Biostable polymer used is polydimethylsiloxane (PDMS)

Question 9

Contraceptive implant:
Where is it placed?
What is active drug?

Answer 9

• Subdermal contraceptive implant (Nexplanon®) is a small flexible plastic rod that’s placed under the skin in your upper (non-dominant) arm
• Implant contains 68 mg of etonogestrel
  released at the following approximate rates:
  − 60-70 micrograms/day in week 5-6
  − 35-45 micrograms/day at the end of the first year
  − 30-40 micrograms/day at the end of the second year
  − 25-30 micrograms/day at the end of the third year
• Implant not visible once inserted, but can be felt
• Contains barium sulphate to enable imaging

Question 10

Contraceptive implant (structure)

Answer 10

• Principal polymer present in the implant is ethylene vinyl acetate copolymer (PEVA) – another biostable polymer
• Skin of the implant is also PEVA but with a lower proportion of the vinyl acetate monomer
  “Ethylene” monomer “Vinyl acetate” monomer