1.

Transdermal drug delivery systems (TDDSs) facilitate the passage of therapeutic

quantities of drug substances through the skin and into the general circulation for
their systemic effects.
2. Evidence of percutaneous drug absorption may be found through measurable
blood levels of the drug, detectable excretion of the drug and/or its metabolites in
the urine, and clinical response of the patient to the therapy.
3. The stratum corneum, being keratinized tissue, behaves as a semipermeable
artificial membrane, and drug molecules penetrate by passive diffusion. It is the
major rate-limiting barrier to transdermal drug transport.
4. Drugs penetrate through passive diffusion. The rate of drug movement across
this layer depends on its concentration in the vehicle, iits aqueous solubility, and
the oilwater partition coefficient between the stratum corneum and the vehicle.
Substances with both aqueous and lipid solubility characteristics are good
candidates for diffusion through the stratum corneum, epidermis, and dermis.
5. Among the factors playing a part in percutaneous absorption are the physical and
chemical properties of the drug, including its molecular weight, solubility,
partitioning coefficient and dissociation constant (pKa), the nature of the carrier
vehicle, and the condition of the skin.
6. a. A chemical skin penetration enhancer increases skin permeability by reversibly
damaging or altering the physicochemical nature of the stratum corneum to reduce
its diffusional resistance.
b. Iontophoresis is delivery of a charged chemical compound across the skin
membrane using an electrical field.
c. Sonophoresis, or high-frequency ultrasound, is also being studied as a means to
enhance transdermal drug delivery. It is thought that high-frequency ultrasound can
influence the integrity of the stratum corneum and thus affect its penetrability.
7. In vivo skin penetration studies may be undertaken for one or more of the
following purposes:
1. To verify and quantify the cutaneous bioavailability of a topically applied
drug
2. To verify and quantify the systemic bioavailability of a transdermal drug
3. To establish bioequivalence of different topical formulations of the same
drug substance
4. To determine the incidence and degree of systemic toxicologic risk
following topical application of a specific drug or drug product

5. To relate resultant blood levels of drug in human to systemic therapeutic

effects

8. Materials in vitro skin penetration studies include limited use of human skin,
animal skins, shed snake skin and Skin Equivalent Testkin.
9. Diffusion cell systems are employed in vitro to quantify the release rates of drugs
from topical preparations. In these systems, skin membranes or synthetic
membranes may be employed as barriers to the flow of drug and vehicle to
simulate the biologic system.
10. TDDSs may be categorized into two types, monolithic and membrane-controlled
systems. Monolithic systems 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. Membrane-controlled transdermal systems
are designed to contain a drug reservoir, or pouch, usually in liquid or gel form; a
rate-controlling membrane; and backing, adhesive, and protecting layers.
11. TDDSs may be constructed of a number of layers, including (a) an occlusive
backing membrane to protect the system from environmental entry and from loss of
drug from the system or moisture from the skin; (b) a drug reservoir or matrix
system to store and release the drug at the skin site; (c) a release liner, which is
removed before application and enables drug release; and (d) an adhesive layer to
maintain contact with the skin after application.
12. Included among the design objectives of TDDSs are the following:
1. Deliver the drug to the skin for percutaneous absorption at therapeutic
levels at an optimal rate
2. Contain medicinal agents having the necessary physicochemical
characteristics to release from the system and partition into the stratum
corneum
3. Occlude the skin to ensure one-way flux of the drug into the stratum
corneum
4. Have a therapeutic advantage over other dosage forms and drug delivery
systems
5. Not irritate or sensitize the skin
6. Adhere well to the patients skin and have size, appearance, and site
placement that encourage acceptance

13. Among the advantages of TDDSs are the following:

1. They can avoid gastrointestinal drug absorption difficulties caused by
gastrointestinal pH, enzymatic activity, and drug interactions with food, drink,
and other orally administered drugs.
2. They can substitute for oral administration of medication when that route
is unsuitable, as with vomiting and diarrhea.
3. They avoid the first-pass effect, that is, the initial pass of a drug substance
through the systemic and portal circulation following gastrointestinal
absorption, possibly avoiding the deactivation by digestive and liver
enzymes.
4. They are noninvasive, avoiding the inconvenience of parenteral therapy.
5. They provide extended therapy with a single application, improving
compliance over other dosage forms requiring more frequent dose
administration.
6. The activity of drugs having a short halflife is extended through the
reservoir of drug in the therapeutic delivery system and its controlled release.
7. Drug therapy may be terminated rapidly by removal of the application
from the
surface of the skin.
8. They are easily and rapidly identified in emergencies (e.g., unresponsive,
unconscious, or comatose patient) because of their physical presence,
features, and identifying markings.
The disadvantages of TDDSs are as follows:
1. Only relatively potent drugs are suitable candidates for transdermal
delivery because of the natural limits of drug entry imposed by the skins
impermeability.
2. Some patients develop contact dermatitis at the site of application from
one or more of the system components, necessitating discontinuation.
14.
A. Transdermal Scopolamine - Scopolamine, 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.
B. Transdermal Nitroglycerin - Nitroglycerin is used widely 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.
C. Transdermal Clonidine - Clonidine 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.
D. Transdermal Nicotine - Nicotine TDDSs are used as adjuncts (e.g., along
with counseling) in smoking cessation programs. They have been shown to
be an effective aid in quitting smoking when used according to productrecommended strategies
E. Transdermal Estradiol - Estradiol 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.
F. Transdermal Contraceptive System - a thin matrix-type transdermal
contraceptive patch consisting of three layers, including a two-ply backing
layer composed of beige flexible film of low-density polyethylene and a
polyester inner ply. The middle layer contains polyisobutylene and polybutene
adhesive, crospovidone, nonwoven polyester fabric, and lauryl lactate as
inactive components; the norelgestromin and ethinyl estradiol are in this
layer. The third layer is the release liner that protects the adhesive layer
during storage and is removed just prior to application
G. Transdermal Testosterone - The testosterone transdermal systems are
available with various delivery rates as hormone replacement therapy in men
who have an absence or deficiency of testosterone
H. Transdermal Methylphenidate - methylphenidate is indicated for attention
deficit hyperactivity disorder in children. The advantage of the transdermal
patch is that it can be applied in the morning 2 hours prior to the time the
effect is needed, that is, at school, and removed later in the day after school
earlier than the 9-hour limit.
15.
1. Percutaneous absorption may vary with the site of application. The
preferred general application site is stated in the package insert for each
product. The patient should be advised of the importance of using the
recommended site and rotating locations within that site.

2. TDDSs should be applied to clean, dry skin that is relatively free of hair and
not oily, irritated, inflamed, broken, or callused.
3. Use of skin lotion should be avoided at the application site because lotions
affect skin hydration and can alter the partition coefficient between the drug
and the skin.
4. TDDSs should not be physically altered by cutting (as in an attempt to
reduce the dose) since this destroys the integrity of the system.
5. A TDDS should be removed from its protective package, with care not to
tear or cut into the unit.
6. A TDDS should be placed at a site that will not subject it to being rubbed
off by clothing or movement.
7. A TDDS should be worn for the full period stated in the products
instructions.
8. The patient or caregiver should be instructed to cleanse the hands
thoroughly before and after applying a TDDS.
9. If the patient exhibits sensitivity or intolerance to a TDDS or if undue skin
irritation results, the patient should seek reevaluation.
10. Upon removal, a used TDDS should be folded in half with the adhesive
layer together so that it cannot be reused.