FINALS TRANSDERMAL

Question 1

_______________________________ are formulations that are
applied to the body surface and are designed to deliver the active
drug across the skin, into the systemic circulation

Answer 1

Transdermal drug delivery system are formulations that are
applied to the body surface and are designed to deliver the active
drug across the skin, into the systemic circulation

Question 2

________________________________ of a drug generally results from direct
penetration of the drug through the stratum corneum , a 10-15 µm
thick layer of flat, partially desiccated non-living tissue

Answer 2

Percutaneous absorption of a drug generally results from direct
penetration of the drug through the stratum corneum , a 10-15 µm
thick layer of flat, partially desiccated non-living tissue

Question 3

The _______________________, being keratinized tissue, behaves as a
semi-permeable artificial membrane, and drug molecules
penetrate by passive diffusion. (Major rate-limiting barrier to
transdermal transport)

Answer 3

The stratum corneum, being keratinized tissue, behaves as a
semi-permeable artificial membrane, and drug molecules
penetrate by passive diffusion. (Major rate-limiting barrier to
transdermal transport)

Question 4

Over most of the body, the stratum corneum has ____________ of
flattened corneocytes with an overall thickness of about 10 mm (6).

Answer 4

Over most of the body, the stratum corneum has 15 to 25 layers of
flattened corneocytes with an overall thickness of about 10 mm (6).

Question 5

Substances with both _______ and ___________________________
are good candidates for diffusion through the stratum corneum,
epidermis, and dermis.

Answer 5

Substances with both aqueous and lipid solubility characteristics
are good candidates for diffusion through the stratum corneum,
epidermis, and dermis.

Question 6

• Increases skin permeability by reversibly damaging or altering the
  physicochemical nature of the stratum corneum to reduce its diffusional
  resistance.
• Among the alterations are increased hydration of the stratum
  corneum, a change in the structure of the lipids and lipoproteins in the intercellular channels through solvent action or denaturation, or
  both

Answer 6

Chemical Enhancers

Question 7

Example of chemical enhacers:

Answer 7

Example: Acetone, Dimethylacetamide, Ethanol, Oleic acid, SLS

Question 8

______________ is delivery of a charged chemical compound across the skin
membrane using an electrical field.

Answer 8

Iontophoresis

Question 9

_____________________, or high-frequency ultrasound, is also being
studied as a means to enhance transdermal drug delivery.

Among the agents examined are hydrocortisone, lidocaine, and
salicylic acid in such formulations as gels, creams, and lotions.

It is thought that high-frequency ultrasound can influence the
integrity of the stratum corneum and thus affect its penetrability.

Answer 9

Sonophoresis

Question 10

_______________________ are designed to
support the passage of drug substances from the surface of the
skin through its various layers and into the systemic
circulation.

Answer 10

TDDSs (also often called transdermal patches)

Question 11

Incorporate a drug matrix layer between the backing and the
frontal layers.

The drug matrix layer is composed of a polymeric material in which the drug is dispersed.
❑The polymer matrix controls the rate at which the drug is released for percutaneous absorption.

Answer 11

Monolithic System

Question 12

❑Designed to contain a drug reservoir, or pouch (liquid/gel form), a rate
controlling membrane, backing adhesive, protecting layer.

❑Advantage: As long as drug solution in the reservoir remains saturated, the
release rate of drug through controlling membrane remains constant.

❑In membrane system: the small quantity of drug is frequently placed in the
adhesive layer to initiate prompt drug absorption and pharmacotherapeutic
effects on skin placement

Answer 12

Membrane-controlled
Transdermal System

Question 13

(protect the system from environmental entry and from loss of drug from the system)

Answer 13

occlusive backing membrane

Question 14

(store and release the drug at the
skin site)

Answer 14

drug reservoir or matrix system

Question 15

which is removed before application and enables drug release

Answer 15

release liner

Question 15

maintain contact with the skin after application

Answer 15

adhesive layer

Question 15

a belladonna alkaloid, is used to prevent travel-related motion sickness and the nausea and vomiting that result from the use of
certain anesthetics and analgesics used in surgery.

Answer 15

Transdermal Scopolamine

Question 16

is a circular flat patch 0.2 mm thick and 2.5 cm2 in area. (4 layer system),

*The TDDS contains 1.5 mg of scopolamine and is designed to deliver approximately 1 mg of scopolamine at an approximately constant rate to the systemic circulation over the 3-day lifetime of the system.

*Priming dose in the adhesive layer: 200mg (to saturate the skin binding site and rapidly brings the plasma concentration to the required steady
state)

Answer 16

Transdermal Scopolamine

Question 17

Patch is worn in a hairless area behind the ear
*Applied at least 4h before the antinausea effect is required
*1 disk worn at a time and may be kept in place for 3 days
*Continued treatment: fresh disk is placed behind the other ear and the
other removed
*Side effect: dryness of the mouth and drowsiness

Answer 17

Transdermal Scopolamine

Question 18

❑Example: Minitran, Nitro-dur, Transderm-Nitro, Nitrodisc
❑Delivers NTG for 24H after application

❑Tolerance is a major factor limiting effectiveness of these systems when used continuously for more than 12H per day
hence an appropriate dosing schedule would include a daily patch on period of 12-14h and a patch off period of 10-12hours.

❑Used in the prophylactic treatment of angina

❑It has a relatively low dose, short plasma half-life, high peak plasma levels, and inherent side effects when taken sublingually, a popular route.

❑It is rapidly metabolized by the liver when taken orally; this first-pass effect is bypassed by the transdermal route.

Answer 18

Transdermal Nitroglycerin

Question 19

❑When a TDDS is applied to the skin, nitroglycerin is absorbed continuously, resulting in active drug reaching the target organs (heart, extremities) before inactivation by the liver.

❑Only a portion of the total nitroglycerin in the system is delivered over the usual 24-hour use period; the remainder serves as the thermodynamic energy source to release the drug and remains in the system.

❑Placed on the chest, back, upper arms or shoulders; free from hair, clean and dry
❑The use of extremities below the knee or elbow is discourages as are the areas that are
abraded or have lesions or cuts

❑Patients should also understand that exercise, sauna (may elevate body temp) increase absorption of NTG

Answer 19

Transdermal Nitroglycerin

Question 20

*For Hypertension
* lends itself to transdermal delivery because of its lipid solubility, high volume of distribution, and therapeutic effectiveness in low plasma concentrations

*The TDDS provides controlled release of clonidine for 7 days. (4 layered patch)

*The system is applied to a hairless area of intact skin on the upper outer arm or chest.

*After application, clonidine in the adhesive layer saturates the skin site.

*Then from the reservoir begins to flow through the rate-controlling membrane and the skin to the systemic circulation.

Answer 20

Transdermal Clonidine

Question 21

*Therapeutic plasma clonidine levels are achieved 2 to 3 days after initial application.

*Application of a new system to a fresh skin site at weekly intervals maintains
therapeutic plasma concentrations.

*If the patch is removed and not replaced with a new system, therapeutic plasma
clonidine levels will persist for about 8 hours and then decline slowly over several
days.

*If the patient has local skin irritation before 7 days of use, the system may be removed
and replaced with a new one applied on a fresh skin site

Answer 21

Transdermal Clonidine

Question 22

Adjuncts in smoking cessation programs (effective aid in quitting smoking)
Example: Nicoderm CQ, Nicotrol, Prostep

oThe TDDSs provide sustained blood levels
replacement therapy to help the patient establish and sustain remission from
smoking.

oMotivation to quit smoking is enhanced through the reduction of withdrawal
symptoms and by partially satisfying the nicotine craving and desired sensory
feelings provided by smoking

oThe commercially available patches contain 7 to 21 mg of nicotine for daily
application during the course of treatment ranging from about 6 to 12 weeks.

Used TDDSs should be discarded properly because the retained nicotine is
poisonous to children and pets.

Answer 22

Transdermal Nicotine

Question 23

_________ is indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause, female hypogonadism, female castration, primary ovarian failure, and atrophic conditions caused by deficient endogenous estrogen production, such as atrophic vaginitis and kraurosis vulvae.

Orally administered is rapidly metabolized by the liver to estrone.

Answer 23

Estradiol

Question 24

Therapy is usually administered on a cycling schedule (3 weeks of therapy followed by 1 week without), especially in women who have not undergone a hysterectomy.

The transdermal system is applied to a clean, dry area of the skin on the trunk of the body, either the abdomen or upper
quadrant of the buttocks.

The patch should not be applied to
the waistline because tight clothing may damage or dislodge it

Answer 24

Transdermal Estradiol

Question 25

Example of Transdermal Contraceptive patch

Answer 25

Ortho Evra (norelgestromin, ethinyl estradiol; Ortho-McNeil)

Transdermal System is a combination contraceptive patch with
a contact surface area of 20 cm2, contains 6 mg of norelgestromin and 0.75 mg of ethyl estradiol.

Question 26

Example of transdermal testosterone

Answer 26

The testosterone transdermal systems Testoderm (Alza) and Androderm
(Watson) are available with various delivery rates as hormone replacement therapy in men who have an absence or deficiency of
testosterone.

Question 26

*(Testoderm TDDS) For optimal absorption, it is applied to clean, dry scrotal skin that has been dry
shaved.
*Scrotal skin is reported to be at least five times as permeable to testosterone as other skin sites
*The TDDS is placed on the scrotum by stretching the scrotal skin with one hand and pressing the
adhesive side of the TDDS against the skin with the other hand, holding it in place for about 10
seconds.
*The TDDS is applied daily, usually in the morning to mimic endogenous testosterone release.
*Optimum serum levels are reached within 2 to 4 hours after application.
*The patch is worn 22 to 24 hours daily for 6 to 8 weeks

Answer 26

Transdermal Testosterone

Question 26

▪It is available as 10-, 15-, 20-, and 30-mg patches nominally delivering the
indicated dose over a 9-hour period.

▪The 10-mg patch actually contains 27.5 mg of the drug, the 15-mg patch contains
41.3 mg, the 20-mg patch contains 55 mg, and the 30-mg patch contains 82.5 mg
of the drug.

▪After 9 hours, the patch is to be removed, folded in on itself (adhesive to
adhesive), and appropriately discarded.

▪There is a dose titration schedule that should be followed initially until the individualized final dosage and wear time are determined.

ex: daytrana

Answer 26

Transdermal Methylphenidate

Question 27

example of patch

Answer 27

The Lidoderm (lidocaine; Endo) 5% patch consists of an adhesive material containing 5% lidocaine, which is applied to a nonwoven
polyester felt backing and covered with a PET film release liner.

The release liner is removed just prior to application.

This product is indicated to treat postherpetic neuralgia.

The patch is applied to intact skin to cover the most painful area.

Question 28

Depending upon the directions for use, the patient can apply up to
three patches, only once for up to 12 hours within a 24-hour period.

This patch may be cut with scissors into a smaller size prior to the
removal of the release liner.

The patient should wash his/her hands prior to and after handling
the lidocaine patch and should avoid eye contact.

After removal, the patch should be immediately disposed of, and in
such a way to avoid accidental exposure to children and animals.

Answer 28

Patches

Question 29

➢A dosage form that is suitable for delivering drugs to
the skin.
➢It consists of a drug that is impregnated into a flexible, durable woven fabric or extruded synthetic material that is coated with an adhesive agent.

➢Typically, the drug is present in the dry state.

Answer 29

Tapes

Question 30

not designed to control the release rate of the drug like transdermal patches.

➢The active drug content is expressed as an amount per surface area with respect to the tape surface exposed to the skin.

➢The use of an occlusive dressing over the tape enhances the rate and extent of delivery of drug to deeper layer of the skin and may result in greater systemic absorption of the drug.

➢For administration, a portion of the tape slightly larger than
the area to be treated is cut and removed from the backing
paper.

➢It should not be applied to folds in the skin but rather to a
smooth skin surface and to dry skin.

Answer 30

Tapes