Uy, Alyssa V.
2BPh
Chapter 11: TRANSDERMAL DRUG DELIVERY SYSTEMS
 Percutaneous Absorption
The absorption of substances from outside the skin to positions
beneath the skin, including entrance into the blood stream
 Penetration of the Skin by Drugs
Drugs may penetrate intact skin after topical application
(a) through the walls of the hair follicles,(b) through the sweat
glands or the sebaceous glands, (c) or between the cells of the
horny layer.
 Are designed to support the passage of drug substances from the
surface of the skin, through its various layers, and into the
systemic circulation.
 The main route for the penetration of drug is generally through
the epidermal layers, rather than through the hair follicles or the
gland ducts, because the surface area of the latter is rather
minute compared to the area of the skin.
 The percutaneous absorption of a drug generally results from
direct penetration of the drug through the stratum corneum.
 Permeation of the laminate barriers in stratum corneum can
occur by diffusion via:
1. Transcellular penetration (across the cells)
2. Intercellular penetration (between the cells)
3. Transappendageal penetration (via hair follicles, sweat and
sebum glands, and pilosebaceous apparatus)
DEPICTION OF FOUR LAYERED THERAPEUTIC
 Factors Affecting Percutaneous Absorption
1. Nature of the drug itself
2. Nature of the vehicle
3. The nature of the skin
4. Presence of moisture
 RESEARCH FINDINGS ABOUT PERCUTANEOUS ABSORPTION
 Drug concentration is an important factor
 Most drug is absorbed through percutaneous absorption when
the drug substance is applied to a larger surface area.
 The drug should have a greater physicochemical attraction to the
skin than to the vehicle in which it is presented in order for the
drug to leave the vehicle in favor the skin.
 Drug absorption appears to be enhanced from vehicles that easily
cover the skin surface, mix readily with the sebum, and bring the
drug into contact with the tissue cells for absorption.
 Vehicles that increase the hydration of the skin generally favor the
percutaneous absorption of drugs.
 The amount of rubbing in or inunction of the topical application
will have a bearing on the amount of drug absorbed, the longer
the period of inunction, the greater the absorption.
 Percutaneous absorption appears to be greater when the drug is
applied to skin with a thin horny layer than with one that is thick.
 The longer the period of time the medicated application is
permitted to remain in contact with the skin, the greater will be
the absorption.
 Multiple-application dosing rather than single bolus applications
can increase drug absorption
 PERCUTANEOUS ABSORPTION ENHANCERS
 Materials used to enhance absorption: surfactants, azone,
dimethylsulfoxide (DMSO), dimethylacetamide,
dimethylformamide, alcohol, acetone, propylene glycol, and
polyethylene glycol.
 Mechanism Of Action For Percutaneous Absorption Enhancers
 Mechanism Of Action
1. Reduction of the resistance of the stratum corneum by
altering its physicochemical properties
2. Alteration of the hydration of the stratum corneum
3. Effecting a change in the structure of the lipids and
lipoproteins in the cellular channels, through solvent action
or denaturation
4. Carrier mechanism in the transport of ionizable drugs
 Percutaneous Absorption Models
2 Categories
1. In vivo - skin penetration; performed in humans
or animal models
Purposes:
a. To verify and quantify the cutaneous bioavailability of
a topical applied drug.
b. To verify and quantify the systemic bioavailability of a
transdermally delivered drug.
c. To establish bioequivalence of different topical
formulations of the same drug substanc
d. To determine incidence and degrees of systemic
toxicologic risk following the topical application of a
specific drug/drug product
2. In Vitro - penetration studies human skin are limited
because of difficulties of procurement, storage, expense,
and variability in permeation. Excised animal skins may
also variable in quality and permeation. Alternative dermal
absorption studies is Living Skin Equivalent (LSE)
Iontophoresis and Sonophoresis
Iontophoresis involves the delivery of charged chemical compounds
across the skin membrane using an applied electrical field.
Examples: lidocaine, amino acids/peptides/insulin, verapamil, and
propanolol
Sonophoresis, or high-frequency ultrasound, is also being studied as a
means to enhance transdermal drug delivery
Examples: hydrocortisone, lidocaine, and salicylic acid in such
formulations as gels, creams and lotions
2 Basic Types of Transdermal Dosing System
1. Those that control the rate of drug delivery to the skin.
2. Those that allow the skin to control the rate of drug
absorption
Objectives of Rate-Controlling TDDS
1. Deliver the drug substances at a controlled rate, to the
intact skin of patients, for absorption into the systemic
circulation.
2. The system should possess the proper physicochemical
characteristics to permit the ready release of the drug
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 substance and facilitate its partition from the delivery
system into the stratum corneum.
3. The system should occlude the skin to ensure the one-way
flux of the drug substance.
4. The transdermal system should have a therapeutic
advantage over other dosage forms and drug delivery
system
5. The system’s adhesive, vehicle, and active agent should be
nonirritating and nonsensitizing to the skin of the patient.
6. The patch should adhere well to the patient’s skin and its
physical size and appearance and placement on the body
should not be a deterrent to use.
7. The system should not permit the proliferation of the skin
bacteria beneath the occlusion.
Advantages of TDDS
1. Avoids gastrointestinal drug absorption difficulties caused by
gastrointestinal pH, enzymatic activity, drug interactions with
food, drinks, or other orally administered drugs.
2. Substitutes for oral administration of medication when that
routes is unsuitable, as in instances of vomiting and/or diarrhea.
3. Avoids first-pass effect, that is, the initial pass of a drug substance
through the systemic and portal circulation following
gastrointestinal absorption (thereby possibly avoiding the drug’s
deactivation by digestive and liver enzymes).
4. Avoids the risks and inconveniences of parenteral therapy and the
variable absorption and metabolism associated with oral therapy.
5. Provides the capacity for multiday therapy with a single
application, thereby improving patient compliance over use of
other dosage forms requiring more frequent dose administration.
6. Extends the activity of drugs having short half-life through the
reservoir of drug present in the therapeutic delivery system and
its controlled release characteristics.
7. Provides capacity to terminate drug effect rapidly (if clinically
desired) by removal of drug application from the surface of the
skin.
8. Provides ease of rapid identification of the medication in
emergencies (e.g. non responsive, unconscious or comatose
patient)
Disadvantages of TDD Systems
1. The transdermal route administration is unsuitable for drugs that
irritate or sensitize the skin.
2. Only relative potent drugs are suitable candidates for transdermal
delivery due to the natural limits of drug entry imposed by the
skin’s impermeability.
3. Technical difficulties are associated with the adhesion of the
systems to different skin types and under various environment
conditions, and the development of rate-controlling drug delivery
features which are economically feasible and therapeutically
advantageous for more than a few drug substances.
General Considerations in the use of TDD Systems
1. The site selected for application should be clean clean, dry, and
hairless (but not shaved)
Example: nitroglycerin - chest; estradiol - buttocks or
abdoment; scopolamine - behind the ear; nicotine –upper
trunk or upper outer arm.
2. The transdermal patch should not be applied to skin that is oily,
irritated, cut, or abraded. This is to assure the intended amount
and rate of transdermal drug delivery and absorption.
3. The patch should be removed from its protective package, being
careful not to tear or cut.
4. The patch should be worn for the period of time stated in the
product’s instructions. Following period, the patch should be
removed and a fresh patch applied as directed.
5. Patches generally may be left on when showering, bathing, or
swimming. Should a patch premature dislodge, an attempt may
be made to reapply it, or it may be replaced with a fresh patch--
the latter being worn for a full time period before it is replaced.
6. The patient should be instructed to cleanse the hands thoroughly
before and after applying the patch. Care should be taken not to
rub the eyes or touch the mouth during handling the patch.
7. If irritation results, patient should seek re-evaluation.
 Other Transdermal Therapeutic Systems
1. Testosteron transdermal system - Testoderm, is available
for hormone replacement in men who have an absence or
deficiency of testosterone.
Dose: 10 mg for delivery of 4 mg/day; 15 mg for
delivery of 6mg/day. The patches are applied to
scrotal skin where optimal absorption occurs. The
patches are worn 22 to 24 hours daily for 6 to 8 weeks.
2. Trans-Ver-Sal - contains 15% salicylic acid in a vehicle
consisting of karaya, a substance known for its non -
irritating and self-adhesive properties. It is use for the
treatment of viral wart infections
 Technology Of Transdermal Delivery Systems (2 Types)
1. Monolithic systems - incorporate a drug matrix layer between
backing and 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 drug is released for
percutaneous absorption.
Ex.: Nitro-Dur and Nitrodisc
2. Membrane controlled transdermal system - are design to contain
a drug reservoir, usually in liquid or gel form, a rate controlling
membrane, and backing, adhesive, and protecting layers
Ex.: Transderm-Nitro and Transderm-Scop
 Examples Of TDD Systems
1. Clonidine - Catapress –TTS
 Four-layered patch:
a. backing layer of pigmented polyester film
b. drug reservoir of clonidine, mineral oil,
polyisobutylene, and colloidal silicon dioxide
c. a microporous polypropylene membrane controlling
the rate of drug delivery
d. an adhesive formulation of agents
 Uses: antihypertensive clonidine at a constant rate for 7
days, once a week dosing in the upper arm or torso.
2. Estradiol - Estraderm
 Four layered patch:
a. transparent polyester film
b. drug reservoir of estradiol and alcohol gelled with
hydroxypropyl cellulose
c. an ethylenevinyl acetate copolymer membrane
d. an adhesive formulation of light mineral and
polyisobutylene
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  Uses: design to release 17 B-estradiol continuously. Applied
twice weekly over a cycle of 3 weeks. The patch is generally
applied to the abdomen, altering sites with each application.
3. Nicotine – Nicotrol
 Multi-layered rectangular patch:
a. outer backing of laminated polyester film
b. rate-controlling adhesive, nonwoven material, and
nicotine, disposable liner removed prior to use - Aid
in smoking cessation programs

4. Nitroglycerin - Deponit
 Nitroglycerin in a matrix of lactose, plasticizer,
polyisobutylene, and aluminized plastic
 Use: to provide controlled release of nitroglycerin COMPONENTS
continuously for a 24 hour period. Patches are applied to  Liner - Protects the patch during storage. The liner is removed
inner part of upper arm, shoulders, or chest. prior to use.
5. Nitroglycerin - Nitro - Dur  Drug - Drug solution in direct contact with release liner
 Nitroglycerin in a gel like matrix composed of glycerin,  Adhesive - Serves to adhere the components of the patch
water, lactose, polyvinyl alcohol, povidone and sodium together along with adhering the patch to the skin
citrate sealed in a polyester foil polyethylene laminate  Membrane - Controls the release of the drug from the reservoir
 Use: same as # 4 and multi-layer patches
6. Scopolamine - Transderm – Scop  Backing - Protects the patch from the outer environment
 Four layered patch:
a. backing layer of aluminized polyester film
b. drug reservoir of scopolamine, mineral oil &
polyisobutylene
c. a microporous polypropylene membrane for rate
delivery of scopolamine
d. adhesive of polyisobutylene, mineral oil, and
scopolamine
 Use: for continuous release of scopolamine over a 3-day
period as required for the prevention of nausea and
vomiting associated with motion sickness. The patch is
placed behind the ear. When repeated administration is
desired, the first patch is removed and the second patch
placed behind the other ear

VIVELLE-DOT
This contains estradiol in a multipolymeric adhesive that helps in the
development and maintenance of the female reproductive system and
secondary sexual characteristics.

NEUPRO
This is a skin patch designed to treat symptoms of early Parkinson's disease.

DENTI PATCH

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This is a band-aid-like patch inserted on your gum to numb it before an
injection

NITRO-DUR
This contains nitroglycerin which is a type of vasodilator. This is used to
prevent chest pain caused by angina. It will not help to stop an episode of
chest pain.

DAYTRANA
This is used to treat Attention Deficit Hyperactivity Disorder (ADHD) in
children six to 12 years of age.

ORTHO EVRA
It is a contraceptive used by women to prevent pregnancy

NICOTINE PATCH
It is used as a temporary aid for smoking-cessation programs. It helps to
control the symptoms of nicotine withdrawal (irritability, headache, fatigue,
insomnia) and thus helps you to concentrate on overcoming the
psychological and behavioral aspects of your smoking habit.

MYLAN ESTRADIOL PATCH

This patch is designed to release Estradiol continuously upon application to
intact skin for the treatment of moderate to severe vasomotor and
vulvovaginal symptoms associated with menopause, and for prevention of
postmenopausal osteoporosis.

NICORETTE PATCH
This contains a low dose of nicotine that is intended to help quit smoking by
reducing the unpleasant nicotine withdrawal effects.

ESTRADERM PATCH
This patch contains estradiol that is a form of estrogen in female sex
hormone the regulates many processes in the body.

NICOTROL PATCH
This helps avoid the discomfort of nicotine withdrawal symptoms when you
quit smoking by giving you a controlled, sustained dose of nicotine

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