D2 Drug delivery for contraception Flashcards
how do barrier methods of contraception work?
prevent sperm and ovum meeting therefore preventing fertilisation and pregnancy
state 3 examples of barrier methods of contraception
- male condom
- female condom
- diaphragm
describe a diaphragm as a method of contraception
silicone dome inserted into the vagina and covers the cervix, acting as a barrier to sperm
what various things do hormonal methods of contraception in order to prevent pregnancy?
combinations of the following things:
- inhibit ovulation
- render endometrium unfavourable for implantation
- render the cervical mucus impenetrable to sperm
- reduce fallopian tube function
what do combined contraceptive pills contain?
- oestrogen and progestogen
- more specifically, synthetic analogues of the endogenous hormones
what are progestogens? what do they do?
- progestogens are natural or synthetic steroid hormones
- they bind to and activate the progesterone receptors
what is progesterone?
- the main progestognenic hormone synthesised by the human body
what are progestins?
synthetic agents
what is the difference between progesterone and progestins?
- progesterone is endogenous
- progestins are synthetic
- both are progestogens
state an example of a synthetic oestrogen found in the combined contraceptive methods
ethinylestradiol
state some examples of synthetic progestogens found in combined contraceptive methods
gestodene
desogestrel
drospirenone
levonorgestrel
norethisterone
in the combined contraceptive pill, how do synthetic oestrogens and progestogens work together to prevent pregnancy?
- inhibit ovulation
- render the endometrium unfavourable for implantation
- make the cervical mucus impenetrable for sperm
describe monophasic combined contraceptive pill regimen, give examples
- contains the same amount of oestrogen and progestogen in all 21 pills
- eg. Gedarel 150/20, Bimizza, Yasmin
describe triphasic combined contraceptive pill regimen, give examples
- 21 day pills with varying quantities of oestrogen (usually just 2 quantities) throughout the packet, and 3 different quantities of progestogen
- eg. Triadene, Synphase, Logynon
describe ED (every day) combined contraceptive pill regimen
- 28 day pill
- 21 of the 28 contain oestrogen and progestogen
- 7 of the pills contain no hormone and are ‘inactive’
- the hormone containing pills can be monophasic or triphasic
advantages of combined contraceptive pill
- reliable (when taken regularly, carefully and consistently)
- easily reversible
- relief of menorrhagia
- reduced risk of anaemia
- protection against endometrial and ovarian cancer
- reduced occurrence of pelvic inflammatory disease
- relief of pre-menstrual symptoms
disadvantages of the combined contraceptive pill
- must be taken regularly, carefully and consistently
- no protection against STIs
- increased risk of circulatory disorders eg. hypertension
- unsuitable for smokers over 35
- increased risk of breast cancer
contraindications of the combined contraceptive pill
- migraines with aura
- breast feeding
- less than 6 weeks postpartum
- hypertension
- current breast cancer
- undiagnosed vaginal bleeding
side effects of the combined contraceptive pill
nausea
headaches
breast tenderness
mood swings
libido changes
breakthrough bleeding
describe the progesterone-only pill (POP)
- contain only a progestogen
- eg. desogestrel, norethisterone, levonorgestrel
- same quantity of progestogen throughout the packet and must be taken every day
how long is the window for missed pills with the POP?
12 hours
what do norethisterone and levonorgestrel pills do to prevent pregnancy?
- inhibit ovulation in some cycles
- render the endometrium unfavourable for implantation
- make the cervical mucus impenetrable for sperm
advantages of POP
- may relieve premenstrual symptoms
- 99% effective when taken carefully
- 12 hour window for missed pills in the case of desogestrel pills
what advantages does the POP have that are different to the combined pill?
- can be taken if breastfeeding
- no evidence of increased risk of venous thromboembolism or hypertension
why can only the POP be taken when breastfeeding and not the combined pill?
the combined pill inhibits lactation but the POP does not
disadvantages of the POP
- needs to be taken carefully
- chance of developing functional ovarian cysts
- increased risk of ectopic pregnancy if it fails
- metabolism affected by drugs which induce cytochrome P450 enzymes
examples of drugs that induce cytochrome P450 enzymes which affects metabolism
- anticonvulsants (eg. carbamazepine, phenytoin, phenobarbital)
- antitubercles (eg. rifampicin)
- antiretrovirals (eg. ritonavir, nevirapine)
- homeopathic medicines (eg. St John’s Wort)
state some reasons for contraceptive failure
- compliance (eg. missing a pill)
- accessibility (can the patient get to the pharmacy to get more?)
- ‘perfect use’ vs. ‘typical use’
explain what is meant by perfect vs typical use of contraceptives
- perfect use is a measure of maximum efficacy and describes use of the contraceptive method as it is intended
- typical use is a measure of effectiveness when a group of people use them normally
what are LARCs? give examples
- long-acting reversible contraceptives
- methods of birth control that provide effective contraception for an extended period without requiring user action
- they do not depend on daily compliance
- eg. IUDs and IUSs
what can the control of the drug plasma concentration lead to and what does this mean in contraceptive terms?
- can lead to constant drug effect
- for contraception, this means a reduced window for unplanned pregnancy to occur (especially if no user action is required, eg. IUS)
how can a reservoir system be used to achieve constant drug effect with hormonal contraception?
- by surrounding a core acting as a saturated reservoir of drug with a membrane that is permeable to the drug
- drug can partition from the core into the membrane and can then diffuse into biological fluids
- whilst the core is saturated, the membrane mediates diffusion and the rate of flux across the membrane is constant
what are monolithic / matrix systems?
contain drug loaded uniformly into a matrix material and release is controlled by diffusion through the matrix material or aqueous pores
what are polymers? what are their physicochemical properties?
- substances of a high molecular weight consisting of repeating monomer units
- physicochemical properties vary considerably depending on their makeup and structure
what does a NuvaRing release in 24 hours?
120 micrograms etonogestrel (progestogen)
15 micrograms ethinylestradiol (oestrogen)
is the NuvaRing a reservoir or matrix device?
- reservoir
- thus drug release follows reservoir-type kinetics
what is NuvaRing?
- a combined contraceptive ring
- composed of ethylene-vinyl acetate (EVA) copolymers
how do vaginal rings prevent pregnancy?
- ovulation is inhibited
- renders endometrium unfavourable for implantation
- makes cervical mucus impenetrable to sperm
when is a vaginal ring in and out of the vagina?
- inserted on the first day of the period
- remains inside for 3 weeks
- removed for 1 week and woman experiences withdrawal bleed
- after this week, a new ring is inserted
how should vaginal rings be kept in pharmacies and for how long?
- in the pharmacy fridge (between 2 and 8 degrees C)
- can be stored this way for 40 months
how many vaginal rings should be dispensed at one time and why?
- 3 months dispensed at once (3 rings)
- rings can remain out of the fridge for no more than 4 months
state an example of a contraceptive patch and describe it briefly
- Evra
- combined method
contraindications of combined contraceptive patch
same as combined pill
- migraines with aura
- breastfeeding
- less than 6 weeks postpartum
- hypertension
- current breast cancer
- undiagnosed vaginal bleeding
what is the effectiveness of the contraceptive patch reduced by?
- enzyme-inducing drugs
- if it becomes partly or fully detached
how often is the contraceptive patch changed? (Evra)
- every 7 days
- after 3 patches / 3 weeks, no patch is applied and a withdrawal bleed occurs
what must the contraceptive patch be applied to?
dry, clean, hairless skin
how does the contraceptive patch prevent pregnancy?
- inhibits ovulation
- renders the endometrium unfavourable for implantation
- makes the cervical mucus impenetrable to sperm
are patches matrix or reservoir systems?
can be both
is the Evra contraceptive patch a reservoir or matrix system?
- matrix
- consists of 3 layers
what are the 3 layers of the Evra contraceptive patch?
- a polyethylene and polyester backing layer
- a middle layer of polyisobutylene / polybutene adhesive, polyester, crospovidone, laurel lactate, 0.75mg ethinylestradiol and 6mg norelgestromin
- a release liner that is removed before application
describe a matrix-type contraceptive type
drug is entrapped within polymer (in contact adhesive)
describe a reservoir-type contraceptive type
drug movement is controlled by rate-controlling membrane
what must be considered regarding the adhesive polymer when designing patches?
- medically approved and tested?
- non-irritating and hypoallergenic?
- water-resistant?
- elastic?
- easily removed with no residue?
- must not react with drug
- drug must not partition into it during storage
why must adhesive polymers in patches be medically approved and tested?
they are next to the skin
why must adhesive polymers in patches be non-irritating and hypoallergenic?
they are next to the skin
why must adhesive polymers in patches be water-resistant?
patient should be able to shower, bathe, swim etc.
why must adhesive polymers in patches be elastic?
for easy movement
why must adhesive polymers in patches not react with the drug?
loss of efficacy and adhesion
why must drug(s) in patches not partition into the adhesive polymer?
causes altered release
what must be considered regarding the backing when designing patches?
must be impermeable
why must the backing of patches be impermeable?
the reservoir must not leak or slowly evaporate because this will change drug release
what 2 options must be considered regarding the reservoir when designing patches?
can be a solution or suspension of drug
what is good about a suspension reservoir in a patch?
- makes the reservoir self-replenishing
- more drug can dissolve to replenish drug released
what must be considered regarding the membrane when designing patches?
must be permeable so that drug can be released into the skin
describe the structure of IUDs and where they are located when in action
- inserted through the cervical canal
- sit within the uterus
- have threads which sit in the vagina which allow a woman to check the device is correctly in place
lifespan of IUDs
many have the lifespan of 5 years and some have a lifespan of 10 years
what is the main mode of action of IUDs and also a secondary effect they produce?
- impair sperm viability
- initiates a ‘foreign body reaction’ involving the release of endometrial prostaglandins and leukocytes, enzymes and copper ions
- secondary effect is that the endometrium is left inhospitable to implantation of an embryo
advantages of IUD
- no drug interactions
- effective immediately
- highly effective
- reversible
disadvantages of IUD
- can result in menorrhagia (heavy periods)
- increased risk of ectopic pregnancy if it fails
- increased risk of pelvic infection during insertion and first year of use
describe the IUS
- a progestogen-secreting device that contains the hormone levonorgestrel
- T-shaped polymer frame with a hormone reservoir around the stem
is the IUS a matrix or reservoir system?
reservoir
describe the reservoir in the IUS
- consists of levonorgestrel in poly(dimethylsolixane) (PDMS)
how does the reservoir of the IUS prevent pregnancy?
- release of levonorgestrel suppresses the endometrium (lining of the uterus) preventing implantation
- cervical mucus is also thicker rendering it impermeable to sperm
state an example of an IUS
Mirena
what property does barium sulphate give to the Mirena IUS?
- frame contains barium sulphate meaning it is radio-opaque
- this means it would show up on x-rays and other scans eg. ultrasound
what role does PDMS play in an IUS?
- it is the polymer in the reservoir core
- it also makes up the outermost rate-controlling polymer membrane so it controls the release of levonorgestrel
what factor affects the drug release rate from the device?
extent of cross-linking between PDMS and levonorgestrel
what has the IUS done other than prevent pregnancy?
relieved many women from menstrual problems such as menorrhagia which previously could only have been managed with hysterectomy
how does the IUS prevent pregnancy?
- suppresses endometrium
- in some women, reduces ovarian function
- thickens cervical mucus so it is impenetrable to sperm
- there is a foreign body reaction to the presence of the IUS
state an example of the contraceptive implant
Nexplanon (currently the only licensed implant in the UK (2025))
how is the contraceptive implant inserted?
with a sterile applicator
is the contraceptive implant a reservoir or matrix system?
- reservoir
- ethylene vinyl acetate (EVA) membrane reservoir system
how does drug release change over time from the contraceptive implant and how long does on last when inserted?
- release rate changes over a 3 year period
- implant must be removed after 3 years
how does the contraceptive implant prevent pregnancy?
- inhibits ovulation
- renders the endometrium unfavourable to implantation
- cervical mucus is altered so it is impenetrable to sperm
advantages of contraceptive implant
- does not require user action
- no side effects associated with oestrogen
- highly effective
- easily reversible
disadvantages of contraceptive implant
- requires a trained professional to insert and remove
- can result in irregular bleeding or ‘spotting’
- side effects include headaches and acne
what do drug release kinetics depend on?
- the design of the system
- ie. matrix, reservoir, or more complicated ones can involve both matrix and reservoir
describe drug release kinetics in matrix systems, what equation do they follow?
- drug is uniformly distributed throughout the polymer matrix
- in general release, they follow the Higuchi equation
describe drug release kinetics in reservoir systems, what law do they follow?
- rate-limiting membrane controls release of drug from a core
- typically display more constant release rates
- follow Fick’s Law of Diffusion
what does this equation relating to reservoir device release kinetics tell us?
the rate of change in concentration of dissolved drug is proportional to the concentration difference between 2 sides of a membrane
notable relationships in release kinetics of reservoir systems
- the release rate from the device is inversely proportional to membrane thickness
- the thicker the membrane, the slower the release
- the greater the area available for molecular diffusion, the greater the release rate
what do each of the terms in this equation relate to? m, t, D, Cs, A, h
this relates to reservoir systems
m: mass of drug
t: time
D: diffusion coefficient
Cs: saturated solubility of drug in the reservoir system
A: the area available for molecular diffusion
h: the membrane thickness
notable relationships in drug release kinetics of matrix devices
- the more porous the matrix, the greater the value of Q (amount released per surface area), therefore the more rapid the release
- the more tortuous the pores, the longer the pathway for diffusion, the lower the value of Q
what assumptions are made in the kinetics of matrix drug release?
- the drug is uniformly dispersed in the matrix
- the drug concentration in the matrix is higher than its solubility
- the drug concentration is 0 at matrix-external medium interface
- rate of release is more rapid initially and slows as the concentration of drug near the polymer surface decreases
