The document discusses various methods of administering hormonal contraceptives and drugs, including subcutaneous injectables, subcutaneous implants, intrauterine devices, and condoms. It provides details on the definition, mechanism of action, advantages, disadvantages, and examples of each method. Deep intramuscular injections and various types of intrauterine devices are explained in more depth. The manufacturing process of condoms is summarized in 7 steps from collection of raw materials to packaging.

1. Dr Liesl Brown
Mrs Liza-Marie Schutte
Department of Pharmacy
University of Limpopo (Medunsa Campus)
Module 3.4: Endocrine and Reproductive Pharmacy (2011)

2. Subcutaneous injectables
Subcutaneous hormonal implants
Intra-uterine devices (IUDs)
Condoms
Sustained release implants
Vaginal creams and pessaries
Transdermal patches

3. By
Dr Liesl Brown

4. Sub-cutaneous injectables
 Definition: SC drug administration = where drugs are injected into the
subcutaneous layer of the skin. This is the easiest and least painful of
injection to administer
 Injected into loose connective and adipose tissue immediately
underneath the skin (drug absorption slower and < predictable
compared to IM route)
 Volume injected: not exceeding 1 ml
 Injection sites:
 Abdomen, upper back, upper arms, lateral upper hips
 Route used when drugs can not be taken orally (drugs more rapidly and
predictably absorbed compared to the oral route)
 Drug distribution – affected by: Examples:
 Site of injection
-Insulin
-Choriogonadotrophin alpha (Ovidrel)
 Body temperature
-Chorionic gonadotrophin (Pregnyl)
 Age of patient -Human menopausal gonadotrophin
 Degree of massaging the injected site (Menopur)

5. Difference between
ID, SC and IM
administrations

6. Sites of
administration for
SC injections (male)

7. Sites of
administration for
SC injections
(female)

8. Subcutaneous hormonal implants
Definition: Implants: solid dosage form which is inserted under the skin
by a small surgical insertion e.g. HRT/contraceptive
• Very small pellets (dense tablet, normally spherical) composed of drug
substance only
• 2-3mm in diameter
• Prepared in aseptic manner to be sterile
• Inserted into body tissues by surgical procedures
• In tissue they are very slowly absorbed over a period of months

9. Subcutaneous hormonal implants
Progesterone only-contraceptives (not available
in SA)
Releases levonorgestrel over period of 5 years
and
Etonorgestrel (active metabolite of desogestrel) over 3 years
Testosterone implant (male hypogonadism):
adequate hormone levels up to 4-5 months

10. Norplant Implants (not available in SA)
 Set of 6 small, plastic capsules (size: matchstick)
 Placed under woman’s upper arm skin
 Contains a progestin (slow release) and no oestrogen
 Efficacy: 5 years or longer
 MOA:
 Thicken cervical mucus (makes it difficult for sperm to pass through)
 Stops ovulation in ½ menses cycles (after 1 year of use)
 Will not work in disrupting an existing pregnancy
 Advantages:
+ Effective 24 hours after insertion
+ Fertility returns immediately after capsules are removed
+ Increased sexual enjoyment (no interruptions)
 Disadvantages:
- Pain upon insertion
- Client cannot start/stop use on her own
- Discomfort (upon and after insertion and removal)

11. Implanton® (1 rod
in stead of 6)
Implanon, a new
implant (Progestin-only
hormone implant -
releases hormone for
prevention of
pregnancy for 3 years)
-uses only 1 rod and is
easier to insert and
remove than Norplant
implants (not available
in SA)

13. Site of
administration for
sc hormonal
implants
Six thin, flexible capsules
filled with levonorgestrel
(LNG) that are inserted just
under the skin of a woman’s
upper arm

14. Site of
administration and
an example of the
SC implants

15. SC levonorgestrel
implants

16. SC hormonal
implants in a
woman’s upper arm

17. Components of a
single rod implant

18. Sustained- release implants
Zoladex® implant
 Contains goserelin acetate a synthetic analogue of LHRH
 Thus it acts as a potent inhibitor of pituitary gonadotropin
secretion
 Used in males for prostate cancer
 10.8 mg implant: release continues over 12 weeks
 3.6 mg implant: 28 days

19. Deep intramuscular contraceptive
injections
Parenteral contraceptives: Progesterone-only
contraceptives (POPs)
Medroxyprogesterone acetate (DMPA), administered 12
weekly, e.g. Depo-Provera®
or
 Norethisterone enanthate (DNET-EN), administered 8
weekly, e.g. Nur-Isterate®

20. Deep intramuscular contraceptive
injections
 MOA:
Mainly stops ovulation
Thickens cervical mucus
Relative low cost
Depo-provera®
 Depot-medroxyprogesterone acetate
 Administered 12 weekly
Nur-Isterate®
 Norethisterone enanthate
 Administered 8 weekly

21. Deep intramuscular
contraceptive injections
 Medroxyprogesterone acetate is insoluble in water
 If administered IM a depot or reservoir of the drug is formed
 The long apparent half-life and long duration of action result from
the slow absorption of the drug from the injection site as a result of
the slow dissolution of the drug from this depot
 Concentrations achieved within 24 hours of administration is
sufficiently high to provide almost immediate protection against
pregnancy
 The concentration of drug increases for approximately three weeks
 Peak concentration of 1 to 7 ng/ml is reached
 Concentration drops to 0.2 ng/ml 5-6 months after administration
 Up to 6 months may be required for fertility to return

22. Deep intramuscular contraceptive
injections
Advantages
 +Very effective (99 %)
 +Does not interfere with the process of love making
 +No daily pill-taking
 +No oestrogen side-effects
Side effects
 -Heavy, prolonged periods / absent periods (may be an
advantage)
 -Headaches
 -Weight gain
 -Delayed return of fertility

23. Deep intramuscular contraceptive
injections
Contraindications for use in women:
 Undiagnosed abnormal vaginal bleeding
 Hormone- dependent cancer
 Migraine sufferers
 Liver problems or a history of thrombosis
 Risk factors for osteoporosis

24. Intrauterine device (IUD)
 Definition: Is a form of birth control that involves an object placed in the
uterus to prevent fertilization of the egg by sperm, inhibit tubular transport
and prevent implantation of the blastocyst into the endometrium
 Long term
 Small, safe and highly effective
 Small, T-shaped device wrapped in copper/contains hormones
 Inserted into the vagina (dr)
 Plastic string tied to the end of the device hangs down through the cervix
into the vagina (use string to check if IUD is in place and also to remove
IUD - dr)
 Types:
 Inert/unmedicated (um-IUD) (USA, aka IUDs)
 Hormonally based/medicated (m-IUD) (UK aka IU system)
 Type 1: PE plastic with progesterone/progestogen attached to the stalk of the
IUD
 Type 2: PE plastic and reservoir of progesterone/progestogen (levonorgestrel)

25. Intrauterine device (IUD)
 Inert/unmedicated (um-IUD) (USA, aka IUDs)
 Made of plastic (polyethylene, PE)
 PE plastic and copper
 PE plastic and a copper base surrounding the PE plastic (copper can be either
single sleeves or wound onto IUD
 Effective, 3-5 (??10) years
 MOA: Copper is toxic to sperm
 Fallopian tubes produce fluid (WBCs, copper ions, enzymes and prostaglandins)
that kills sperm

26. Intrauterine device (IUD)
 Hormonally based/medicated (m-IUD) (UK aka IU system)
 Type 1: PE plastic with progesterone/progestogen attached to the stalk of the
IUD
 The progesterone/progestogen is surrounded by a silica membrane which results
in a controlled rate of release of the progesterogen/progestogen
 Effective: 5 years
 Type 2: PE plastic and reservoir of progesterone/progestogen (levonorgestrel)
 Mirena®
 Effective : 5 years
 MOA: prevents fertilisation of the egg
 Prevents fertilisation by damaging/killing sperm
 Makes the mucus thick and sticky (sperm cannot get to uterus)
 Thick growth of the endometrium (results in a lining that is a poor place for a
fertilised egg to implant/grow)
 Hormone: progesterone (levonorgestrel): reduces menstrual bleeding and cramping

27. An example of a
Mirena® IUD
Mirena is a new type of IUD
that gradually releases the
progestin levonorgestrel.
Progestin-releasing IUDs
make menstruation lighter
and less painful. Mirena has
been approved for 5 years of
use in more than 100
countries.

28. An example of an
IUD containing
levonorgestrel and
copper
An intrauterine device (IUD)
is a small, plastic, T-shaped
device that is inserted into
the uterus to prevent
pregnancy. IUDs contain
copper or the hormone
levonorgestrel (LNg). Plastic
strings tied to the end of the
IUD hang down through the
opening of the uterus
(cervix) into the vagina.

29. An example of an
IUD in the uterus

30. An example of a
single cylinder IUD
that is anchored in
the fundus of the
uterus
Frameless IUDs, such as
GyneFix, do not have the
plastic T-shaped frame of
conventional IUDs. Instead,
they consist of several copper
cylinders tied together on a
string. The device is
anchored 1 centimeter deep
into the fundus of the uterus.

31. Other dosage forms: Condoms
 Definition:
A male condom is a sheath, or covering, made of
latex/(polyurethane/lamb cecum) materials, made to fit over a man’s
erect penis to prevent his sperm of being expelled into an orifice of
another person (e.g. vagina), thereby preventing pregnancy
A female condom is a latex/polyurethane sheath or covering, which is
placed into the vagina to prevent sperm from entering a woman’s
vagina/uterus, thus preventing pregnancy
 MOA: Cover the cervix or the penis to block sperm from entering the cervical
canal

32. Other dosage forms: Condoms
 Advantages:
 +Prevents STIs and HIV/AIDS
 +Easily obtainable and comes in a variety of sizes and types
 +Enables males to take responsibility in preventing pregnancy and STIs
 +Easy to use
 +Immediately effective
 Disadvantages:
 -Latex and lubricant allergy
 -Interruption in love making process
 -Male erection needed
 -Embarrassment (purchase, use, put on/take off)
 Efficacy: 10 - 15 pregnancies per 100 women per year as typically used

33. Manufacturing of condoms
 Lamb cecum (‘skin’ condoms)
 New Zealand – raises large numbers of sheep – primary sources of
lamb cecum
 Manufacturing stays the same since Schmid 1st manufactured
condoms
 Cecums are washed, defatted and salted
 Polyurethane condoms
 Female (expensive: $3 vs $0.64 for male condom)
 Male condoms (new advances, 1994)
 Just as strong as latex (female condom 40x stronger than latex)
 1/10 as thick as latex condom
 Recommended for latex sensitive persons
 Latex condoms

34. Step 1:
Step 2:
Collection of
Compounding
raw material
Rubber trees (Brazil, SA Asia, West Africa)
Collect sap (containing latex)
Step 7: Step 3:
Packaging Storage
Latex = emulsion or dispersion of small
rubber particles in water
-Add to the shelve
Latex condoms (end product) also life of latex
contains: -Makes rubber less
-Antifungal/antibacterial agents biodegradable
-ZnO2 and sulfur (vulcanization agent) (trash rather than
-K-laurate (stabilizer)
Step 6: Steptoilet)
4:
-Ammonia (anticoagulant)
Testing Dipping
-Antioxidants
-Preservatives and pigments
Step 5:
Tumbling

35. Step 1:
Step 2:
Collection of
Compounding
raw material
Ingredients added that must bind to
the rubber particles in the latex
Step 7: Step 3:
Packaging Storage
Chemical additives are added to
make a paste and mix this with the
liquid latex
Step Done:
6: -Strength Step 4:
Testing -Reliability Dipping
-Lower allergenic potential
Step 5:
Tumbling

36. Step 1:
Step 2:
Collection of
Compounding
raw material
Step 7: Step 3:
Packaging Storage
Content is then loaded into drums
for 7 days
-vulcanized (heated) chemically to
strengthen rubber bonds
-so that the O2 (in the mixture (can
escape)
Step 6: Step 4:
Testing Dipping
Step 5:
Tumbling

37. Step 1:
Step 2:
Collection of
Compounding
raw material
Belt 7:
Step
drags and rotates glass
Packaging
Step 3:
Storage
rods/mandrels through a series of
dips into the latex compound
-makes condoms thick
Done: enough
-Latex is evenly spread (repeat x2-3) -dries water (> water,
-After each dip the latex is hot air dried so thinner condom)
that:
completes 6: chemical reactions and
Step the Step 4:
Testing
ensures strength and stability Dipping
Ring of latex at the base ofStep 5:
each
Tumbling
condom is made

38. A continuous line of clean
glass formers are dipped into
the latex, where they become
coated. The formers are
rotated to ensure the latex is
evenly spread.
After drying, the formers are
dipped for a second time.

39. Step 1:
Step 2:
Collection of
raw material
Compounding Remove
-odours
Mandrels travel through a tunnel oven -allergens
-vulcanize the condoms -pathogens
Step 7:
Condoms are removed and washed Step 3:
Packaging Storage
Condoms
Placed in a special tumble drier coated with
talc/cornstarch,
silica or
magnesium
Step 6: Step 4: carbonate
Testing Dipping
-prevent it
sticking
Step 5:
together
Tumbling -easier to unroll

40. Step 1: Tested after several days
Step 2:
Collection of
Compounding
raw material
Batches are made and tested
1. Inflation test 2. Water leakage
Step 7:
test Step 3:
Packaging Storage
Step 6: Step 4:
Testing Dipping
Step 5:
Tumbling

41. Step 1: Tested after several days
Step 2:
Collection of
Compounding
raw material
Batches are made and tested
1. Inflation test
Step 7: Step 3:
Packaging Most important test because Storage
it tests the elasticity and burst
strenght
(NB: determines a parameter
of the condom’s ability not to tear during sex)
Stretched beyond 1.5 cubic feet (size of a watermelon)
Step 6: Step 4:
Testing International latex standard: 18 litres
Dipping
Step 5:
Tumbling

42. Inflation tests measure how
much air a condom can hold
-- and how far it can stretch -
- before it breaks.

43. Step 1: Tested after several days
Step 2:
Collection of
Compounding
raw material
Batches are made and tested
2. Water leakage test
Step 7: Step 3:
Packaging Condoms are filled with 300 ml Storage
of water and inspected for pin-
sized holes by rolling it over blotter
paper
as well as electronically
-mandrel is mounted on a stainless steel charged
Step 6: mandrel Step 4:
Testing -mandrel is then passed over a soft conductive brush
Dipping
If there is pinholes, a circuit will be established and the
Step 5:
machine will reject the condom
Tumbling

44. Water leakage test –
condoms are filled with 300
ml of water and inspected for
pin-sized holes

45. Step 1: Condoms that have passed the tests
Step 2:
Collection of
Compounding
raw material
rolled
Lubricant/spermacide added by a meter pump (last
Step 7:
step) Step 3:
Packaging Storage
Condom sandwiched between 2 layers of laminated foil
Top wrap is added to the foiling process
Put on conveyor belt - exterior packaging (box)
Step 6: Step 4:
Testing Dipping
!! amount of N9 used in condoms
- little effect during sexual activity
Step 5: -Since it can cause vaginal
Lubricated condoms - silicone Tumbling irritation - make s disease transfer
Spermicidally lubricated condoms - more likely, it can
nonoxynol-9 (N9), in the lubricant do more harm than good

46. Step 1: Condoms that have passed the tests
Step 2:
Collection of
Compounding
raw material
rolled
Lubricant/spermacide added by a meter pump (last step)
Step 7: Step 3:
Packaging Condom sandwiched between 2 layers of laminated foil
Storage
Top wrap is added to the foiling process
Packaging done:
-air out
Put on conveyor belt
-UV light out
-exterior packaging (box)
-square better
Step 6: Step 4:
Testing Dipping
than triangular
(less damage)
Step 5: Expiry date: 5
Tumbling years

47. Step 1:
Step 2:
Collection of
Compounding
raw material
Step 7: Step 3:
Packaging Storage
Durex:
-Water leak testing: Sample of over 2,000,000 condoms per month
-Air inflation test: International latex standard: 18 L. Durex min. latex
standard: 22 L. Typically Durex condoms will expand to 40 L. Sample of
ca. 500,000 condoms per month
Step 6: Step 4:
If the condoms fail on any of the tests the entire batch –
Testing Dipping
which can be up to 432,000 condoms - is discarded!
Step 5:
Tumbling

48. This is when any lubricant
and flavoring that’s going to
be used is injected into the
foil at the same time.

49. Testing of a male
polyurethane
condom
At a manufacturing plant in
Colombia, a technician tests
the Unique brand
polyurethane condom.
Polyurethane condoms have
a longer shelf life than latex
condoms.

50. Condoms – Quality Control
 Class II Medical Devices (FDA)
 Inspection once every 2 years
 Condom dipping machines may not stop (clogged and rusted)
 Measurements:
 Length: 150-200 mm
 Width: 47-54 mm
 Thickness: 0.03-0.09 mm (most condoms range: 0.002 and 0.0024 mm)
 Weight: not > 2 g
 Tensile strength: 15 000 pounds psa
 Elongation before breakage: 625%
 Checks: cracking, molding, drying/sticking latex
 Lots will not pass:
 > 4% failure with respect to the above dimensions
 2.5% with respect to tensile strength and elongation
 0.4% due to leakage

51. Condoms – Quality Control
 Class II Medical Devices (FDA)
 Inspection once every 2 years
 Condom dipping machines may not stop (clogged and rusted)
 Measurements:
 Length: 150-200 mm
 Width: 47-54 mm (when laid flat)
 Thickness: 0.03-0.09 mm (most condoms range: 0.002 and 0.0024 mm)
 Weight: not > 2 g
 Tensile strength: 15 000 pounds psa
 Elongation before breakage: 625%
 Checks: cracking, molding, drying/sticking latex
 Lots will not pass:
 > 4% failure with respect to the above dimensions
 2.5% with respect to tensile strength and elongation
 0.4% due to leakage

52. Condoms – Quality Control
 Class II Medical Devices (FDA)
 Inspection once every 2 years
 Condom dipping machines may not stop (clogged and rusted)
 Measurements:
 Length: 150-200 mm
 Width: 47-54 mm
 Thickness: 0.03-0.09 mm (most condoms range: 0.002 and 0.0024 mm)
 Weight: not > 2 g
 Tensile strength: 15 000 pounds psa
 Elongation before breakage: 625%
 Checks: cracking, molding, drying/sticking latex
 Lots will not pass:
 > 4% failure with respect to the above dimensions
 2.5% with respect to tensile strength and elongation
 0.4% due to leakage

53. Condoms – Quality Control
 Class II Medical Devices (FDA)
 Inspection once every 2 years
 Condom dipping machines may not stop (clogged and rusted)
 Measurements:
 Length: 150-200 mm
 Width: 47-54 mm
 Thickness: 0.03-0.09 mm (most condoms range: 0.002 and 0.0024 mm)
 Weight: not > 2 g
 Tensile strength: 15 000 pounds psa
 Elongation before breakage: 625%
 Checks: cracking, molding, drying/sticking latex
 Lots will not pass:
 > 4% failure with respect to the above dimensions
 2.5% with respect to tensile strength and elongation
 0.4% due to leakage

54. Female condom
 The female condom is up to 95% effective. But it can sometimes slip or
split when used incorrectly
 Advantages:
 +No side effects
 +Can help protect against STIs, including HIV/AIDS
 +Can be put in anytime before sex
 Disadvantages:
 -Putting them in can interrupt sex
 -Some people claim condoms reduce sensitivity during sex
 -Not widely available

55. The female condom

56. The female condom

57. How to use a male condom
 Always follow the instructions in the condom pack.
Check the expiry date on the condom wrapper before
you use it. Tear the wrapper open from the serrated
edge and handle the condom carefully, as it can be
damaged by fingernails and sharp objects like
jewellery and body piercings.

58. Either of you can put the
condom on the erect penis.
Just make sure you put the
condom on before you have
any sexual activity. This helps
to prevent an unplanned
pregnancy and the possibility
of catching sexually
transmitted infections.

59. Check the roll is on the
outside. If it’s on the inside,
the condom is inside out.
Squeeze the teat end of the
condom so there’s no air
trapped inside.

60. Still squeezing the teat, put
the condom on top of the
penis and roll it down with
your other hand. If it starts to
roll back up during sex, just
roll it back down again
straight away. If it comes off,
stop and put a new condom
on.

61. Soon after ejaculation, and
while the penis is still erect,
the condom should be held
firmly in place at the base of
the penis before withdrawal.
Then just take it off, wrap it
in a tissue and put it in the
bin. Please don’t flush it
down the toilet.

62. By
Mrs Liza-Marie Schutte

63. Vaginal dosage forms
 Formulation:
 Tablets, capsules, pessaries, solutions, sprays, foams,
creams, ointments
 Due to low moisture environment (in the vagina) –
additives are used to improve e.g. disintegration of
vaginal tablets
 Bicarbonate + an organic acid which results in CO2 release
 Filler: lactose (converted by vaginal flora to lactic acid,
resulting in a pH of 4-4.5
 Vaginal pessaries
 Prepared with: glycerol-gelatin bases (tolerated well)
 PE glycols – less common (irritation)
 Fatty excipients (not used much)

64. Vaginal creams and pessaries
 Definition: Pessaries: solid dosage forms for vaginal
insertion. They are used for both local and systemic effects
 Administration
 Mainly used for local effects (Trichomonas/Candida)
 Some drugs are administered for systemic effects
 Some drugs have a higher BA compared to the oral route (drug
immediately enters the systemic circulation without passing the
metabolizing liver)
 Vagina well suited for absorption for systemic effects (vast network of
blood vessels)
 Few drugs are administrated via this route
 Oestrogens and prostaglandin analogues (creams or hydrogels)
 Progesterone (vaginal suppository/pessary)

65. Vaginal creams and pessaries (cont)
Canesten® VC and pessaries
 Use to control vaginal infections
 Contains clotrimazole

66. Vaginal creams and pessaries (cont)
Cirone® vaginal gel
 Progesterone 90mg/application (8%)
 For infertility due to inadequate luteal phase
 Dosage: 1 application daily, starting after
documented ovulation or on day 18-21 of cycle.

67. Vaginal creams and pessaries (cont)
Cyclogest® pessary
 Progesterone 200mg
 For corpus luteum insufficiency
 Dosage: insert 200mg pessary daily; may be
increased to 400mg BD

68. Vaginal creams and pessaries (cont)
Orthoforms®
 Pessaries use for contraception

69. Transdermal patches
 Device which releases drug to the skin at a controlled
rate well below the maximum that the tissue can accept.
 Thus, the device, not the stratum corneum, controls the
rate at which drug diffuses through the skin.

70. Transdermal patches (cont)
Claimed advantages
 Variables influenced by gut absorption e.g. changes in pH along GI
tract, food/fluid intake, stomach emptying time and intestinal motility
are eliminated
 Drug enters systemic circulation directly, eliminating ‘first past’ effect
 Controlled, constant drug administration.
 This continuity may permit the use of drugs with short half-lives and
improve patient compliance
 Transdermal route can use drugs with low therapeutic index

71. Transdermal patches (cont)
Evra® contraceptive patch
• Contains norelgestromin 6 mg, ethinylestradiol
0.6mg which delivers norelgestromin 150 µg and
ethinylestradiol 20 µg in 24 hours
• Apply first patch on day 1 of
menstruation. Patch is effective
immediately
• Apply a new patch weekly for three
consecutive weeks (i.e. on days
1, 8 and 15) followed by one week
patch-free (days 22-28)
• Commence the next patch cycle after
no more than 7 patch-free days

72. Transdermal patches (cont)

73. Transdermal patches (cont)
Evorel Conti® patch for hormone replacement therapy
 Suitable for woman with a uterus
 Contains estradiol hemihydrate 3.2 mg, norethisterone
acetate 11.2 mg
 Release in 24 hours: estradiol 50µg, norethisterone
acetate 170 µg
 Apply twice weekly without interuption to clean, dry, intact
skin of the trunk below the waist (not to breasts). Do not
apply twice in succession to the same site

74. References
 Aulton, M.E. (editor). Pharmaceutics. The Science of Dosage form
Design. 2007. London: Churchill Livingstone
 Desai, A., Lee, M., Gibaldi’s Drug Delivery Systems in
Pharmaceutical Care. 2007. Maryland: American Society of health-
System Pharmacists
 Hatcher, R.A., et al. The Essentials of Contraceptive Technology.
2001. Baltimore: John Hopkins Population Information Program
Websites
 http://www.pharmainfo.net/reviews/development-fabrication-and-evaluation-transdermal-
drug-delivery-system-review
 http://informahealthcare.com/doi/abs/10.1081/DDC-100105179
 http://info.k4health.org/pr/m19/m19chap2.shtm
 lhttp://www.netdoctor.co.uk/sex_relationships/facts/contraceptiveinjection.htm
 http://www.rxlist.com/drug-slideshows/article.htm
 http://home.intekom.com/pharm/hmr/cyclogst.html (SA electronic package inserts)
 http://www.bing.com/images/search?q=transdermal+patch&form=QBIR#