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Uy, Alyssa V.

2BPh
Chapter 11: TRANSDERMAL DRUG DELIVERY SYSTEMS  Multiple-application dosing rather than single bolus applications
 Percutaneous Absorption can increase drug absorption
The absorption of substances from outside the skin to positions
beneath the skin, including entrance into the blood stream  PERCUTANEOUS ABSORPTION ENHANCERS
 Penetration of the Skin by Drugs  Materials used to enhance absorption: surfactants, azone,
Drugs may penetrate intact skin after topical application dimethylsulfoxide (DMSO), dimethylacetamide,
(a) through the walls of the hair follicles,(b) through the sweat dimethylformamide, alcohol, acetone, propylene glycol, and
glands or the sebaceous glands, (c) or between the cells of the polyethylene glycol.
horny layer.
 Are designed to support the passage of drug substances from the  Mechanism Of Action For Percutaneous Absorption Enhancers
surface of the skin, through its various layers, and into the  Mechanism Of Action
systemic circulation. 1. Reduction of the resistance of the stratum corneum by
 The main route for the penetration of drug is generally through altering its physicochemical properties
the epidermal layers, rather than through the hair follicles or the 2. Alteration of the hydration of the stratum corneum
gland ducts, because the surface area of the latter is rather 3. Effecting a change in the structure of the lipids and
minute compared to the area of the skin. lipoproteins in the cellular channels, through solvent action
or denaturation
 The percutaneous absorption of a drug generally results from
4. Carrier mechanism in the transport of ionizable drugs
direct penetration of the drug through the stratum corneum.
 Percutaneous Absorption Models
 Permeation of the laminate barriers in stratum corneum can
2 Categories
occur by diffusion via:
1. In vivo - skin penetration; performed in humans
1. Transcellular penetration (across the cells)
or animal models
2. Intercellular penetration (between the cells)
Purposes:
3. Transappendageal penetration (via hair follicles, sweat and
a. To verify and quantify the cutaneous bioavailability of
sebum glands, and pilosebaceous apparatus)
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
DEPICTION OF FOUR LAYERED THERAPEUTIC 2. In Vitro - penetration studies human skin are limited
because of difficulties of procurement, storage, expense,
and variability in permeation. Excised animal skins may
 Factors Affecting Percutaneous Absorption
also variable in quality and permeation. Alternative dermal
1. Nature of the drug itself
absorption studies is Living Skin Equivalent (LSE)
2. Nature of the vehicle
3. The nature of the skin
Iontophoresis and Sonophoresis
4. Presence of moisture
Iontophoresis involves the delivery of charged chemical compounds
across the skin membrane using an applied electrical field.
 RESEARCH FINDINGS ABOUT PERCUTANEOUS ABSORPTION
Examples: lidocaine, amino acids/peptides/insulin, verapamil, and
 Drug concentration is an important factor
propanolol
 Most drug is absorbed through percutaneous absorption when
the drug substance is applied to a larger surface area.
Sonophoresis, or high-frequency ultrasound, is also being studied as a
 The drug should have a greater physicochemical attraction to the
means to enhance transdermal drug delivery
skin than to the vehicle in which it is presented in order for the
Examples: hydrocortisone, lidocaine, and salicylic acid in such
drug to leave the vehicle in favor the skin.
formulations as gels, creams and lotions
 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.
2 Basic Types of Transdermal Dosing System
 Vehicles that increase the hydration of the skin generally favor the
1. Those that control the rate of drug delivery to the skin.
percutaneous absorption of drugs.
2. Those that allow the skin to control the rate of drug
 The amount of rubbing in or inunction of the topical application absorption
will have a bearing on the amount of drug absorbed, the longer
the period of inunction, the greater the absorption.
Objectives of Rate-Controlling TDDS
 Percutaneous absorption appears to be greater when the drug is 1. Deliver the drug substances at a controlled rate, to the
applied to skin with a thin horny layer than with one that is thick. intact skin of patients, for absorption into the systemic
 The longer the period of time the medicated application is circulation.
permitted to remain in contact with the skin, the greater will be 2. The system should possess the proper physicochemical
the absorption. characteristics to permit the ready release of the drug

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substance and facilitate its partition from the delivery 2. The transdermal patch should not be applied to skin that is oily,
system into the stratum corneum. irritated, cut, or abraded. This is to assure the intended amount
3. The system should occlude the skin to ensure the one-way and rate of transdermal drug delivery and absorption.
flux of the drug substance. 3. The patch should be removed from its protective package, being
4. The transdermal system should have a therapeutic careful not to tear or cut.
advantage over other dosage forms and drug delivery 4. The patch should be worn for the period of time stated in the
system product’s instructions. Following period, the patch should be
5. The system’s adhesive, vehicle, and active agent should be removed and a fresh patch applied as directed.
nonirritating and nonsensitizing to the skin of the patient. 5. Patches generally may be left on when showering, bathing, or
6. The patch should adhere well to the patient’s skin and its swimming. Should a patch premature dislodge, an attempt may
physical size and appearance and placement on the body be made to reapply it, or it may be replaced with a fresh patch--
should not be a deterrent to use. the latter being worn for a full time period before it is replaced.
7. The system should not permit the proliferation of the skin 6. The patient should be instructed to cleanse the hands thoroughly
bacteria beneath the occlusion. 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.
Advantages of TDDS
 Other Transdermal Therapeutic Systems
1. Avoids gastrointestinal drug absorption difficulties caused by 1. Testosteron transdermal system - Testoderm, is available
gastrointestinal pH, enzymatic activity, drug interactions with for hormone replacement in men who have an absence or
food, drinks, or other orally administered drugs. deficiency of testosterone.
2. Substitutes for oral administration of medication when that Dose: 10 mg for delivery of 4 mg/day; 15 mg for
routes is unsuitable, as in instances of vomiting and/or diarrhea. delivery of 6mg/day. The patches are applied to
3. Avoids first-pass effect, that is, the initial pass of a drug substance scrotal skin where optimal absorption occurs. The
through the systemic and portal circulation following patches are worn 22 to 24 hours daily for 6 to 8 weeks.
gastrointestinal absorption (thereby possibly avoiding the drug’s 2. Trans-Ver-Sal - contains 15% salicylic acid in a vehicle
deactivation by digestive and liver enzymes). consisting of karaya, a substance known for its non -
4. Avoids the risks and inconveniences of parenteral therapy and the irritating and self-adhesive properties. It is use for the
variable absorption and metabolism associated with oral therapy. treatment of viral wart infections
5. Provides the capacity for multiday therapy with a single
application, thereby improving patient compliance over use of  Technology Of Transdermal Delivery Systems (2 Types)
other dosage forms requiring more frequent dose administration. 1. Monolithic systems - incorporate a drug matrix layer between
6. Extends the activity of drugs having short half-life through the backing and frontal layers. The drug matrix layer is composed
reservoir of drug present in the therapeutic delivery system and of a polymeric material in which the drug is dispersed. The
its controlled release characteristics. polymer matrix controls the rate at which drug is released for
7. Provides capacity to terminate drug effect rapidly (if clinically percutaneous absorption.
desired) by removal of drug application from the surface of the Ex.: Nitro-Dur and Nitrodisc
skin. 2. Membrane controlled transdermal system - are design to contain
8. Provides ease of rapid identification of the medication in a drug reservoir, usually in liquid or gel form, a rate controlling
emergencies (e.g. non responsive, unconscious or comatose membrane, and backing, adhesive, and protecting layers
patient) Ex.: Transderm-Nitro and Transderm-Scop

Disadvantages of TDD Systems  Examples Of TDD Systems


1. The transdermal route administration is unsuitable for drugs that 1. Clonidine - Catapress –TTS
irritate or sensitize the skin.  Four-layered patch:
2. Only relative potent drugs are suitable candidates for transdermal a. backing layer of pigmented polyester film
delivery due to the natural limits of drug entry imposed by the b. drug reservoir of clonidine, mineral oil,
skin’s impermeability. polyisobutylene, and colloidal silicon dioxide
3. Technical difficulties are associated with the adhesion of the c. a microporous polypropylene membrane controlling
systems to different skin types and under various environment the rate of drug delivery
conditions, and the development of rate-controlling drug delivery d. an adhesive formulation of agents
features which are economically feasible and therapeutically  Uses: antihypertensive clonidine at a constant rate for 7
advantageous for more than a few drug substances. days, once a week dosing in the upper arm or torso.
2. Estradiol - Estraderm
General Considerations in the use of TDD Systems  Four layered patch:
1. The site selected for application should be clean clean, dry, and a. transparent polyester film
hairless (but not shaved) b. drug reservoir of estradiol and alcohol gelled with
Example: nitroglycerin - chest; estradiol - buttocks or hydroxypropyl cellulose
abdoment; scopolamine - behind the ear; nicotine –upper c. an ethylenevinyl acetate copolymer membrane
trunk or upper outer arm. 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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