TRANSDERMAL DRUG DELIVERY SYSTEMS advantages, disadvantages

TRANSDERMAL DRUG DELIVERY SYSTEMS advantages, disadvantages

1. TRANSDERMAL DRUG
DELIVERY SYSTEMS
PRESENTED BY
NIVEDITHA G
1
st
sem Mpharm
Dept Of Pharmaceutics
NARGUND COLLEGE OF PHARMACY

5. Eliminates potential pain associated
with injections
No first pass metabolism in liver
Eliminates gastrointestinal side effect
Improves patient compliance due to
simpler, pain free delivery
Potential for home administration
Benefits of TDDSs

6. 1.They can avoid gastrointestinal drug
absorption difficulties caused by
gastrointestinal pH, enzymatic activity
and drug interactions with food, drink,
or other orally administered drugs.
2.They can substitute for oral
administration of medication when that
route is unsuitable, as in instances of
vomiting and/or diarrhea.
The advantages of TDDSs are:

7. 3.Theyavoidthefirst-passeffect,thatis,
theinitialpassofadrugsubstance
throughthesystemicandportalcirculation
followinggastrointestinalabsorption,
therebypossiblyavoidingthedrug’s
deactivationbydigestiveandliver
enzymes.
4.Thesystemsarenoninvasive,avoiding
theinconvenienceofparenteraltherapy.

8. They provide extended therapy with a
single application, thereby improving
patient compliance over other dosage
forms requiring more frequent dose
administration.
6. The activity of drugs having short
half-lives is extended through the
reservoir of drug present in the
therapeutic delivery system and its
controlled release characteristics.

9. Drug therapy may be terminated rapidly
by removal of the application from the
surface of the skin.
8. Ease of rapid identification of the
medication in emergencies (e.g.,
nonresponsive, unconscious, or
comatose patient) due to the physical
presence, features and identifying-
markings on the TDDS.

10. The disadvantages of TDDSs are:
1. Only relatively potent drugs are suitable
candidates for transdermal delivery due to
the natural limits of drug entry imposed by
the skin’s impermeability.
2.Some patients may develop contact
dermatitis at the site of application due to
one or more of the system components,
necessitating discontinuation.

12. 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.
TRANSDERMAL DRUGDELIVERY SYSTEM

13. TRANSDERMAL DELIVERY SYSTEMS
Are designed to support the
passage of drug substances from
the surface of the skin, through its
various layers, and into the
systemic circulation.

14. 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.
PENETRATION OF THE SKIN BY
DRUGS

15. 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)
TRANSDERMAL DRUG DELIVERY SYSTEMS

16. DEPICTION OF FOUR LAYEREDTHERAPEUTIC

17. 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
TRANSDERMAL DRUG DELIVERY SYSTEMS

18. 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.
RESEARCH FINDINGS ABOUT PERCUTANEOUS
ABSORPTION

19. 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
RESEARCH FINDINGS ABOUT PERCUTANEOUS
ABSORPTION

20. Materials used to enhance
absorption:surfactants,
azone, dimethylsulfoxide
(DMSO), dimethylacetamide,
dimethylformamide, alcohol,
acetone, propylene glycol, and
polyethylene glycol.
PERCUTANEOUS ABSORPTION
ENHANCERS

21. 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.
Mechanism Of Action For Percutaneous
Absorption Enhancers

22. 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.
Percutaneous Absorption Models

23. 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)
Percutaneous Absorption Models

24. Iontophoresis and Sonophoresis
Iontophoresisinvolves 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

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

26. Iontophoresis-
enhanced
transdermal
delivery has
shown some
promise as a
means of
peptide and
protein
administration.

27. A number of drugs have been the
subject of iontophoretic studies,
they include
lidocaine
dexamethasone
amino acids,
peptides
insulin
Verapamil
Propranolol

28. Sonophoresis, is a process that
exponentially increases the absorption of
topical compounds (transdermal delivery)
with high-frequency ultrasound.
Sonophoresisoccurs because ultrasound
waves stimulate micro-vibrations within
the skin epidermis and increase the
overall kinetic energy of molecules
making up topical agents.

30. It is thought that high-frequency
ultrasound can influence the integrity of
the stratum corneumand thus affect its
penetrability.
Among the agents examined are
hydrocortisone,
lidocaine,
salicylic acid
in such formulations as gels, creams,
and lotions.

31. This method involves the application of a magnetic field which acts as an external driving force
to enhance the diffusion of a diamagnetic solute across the skin.
Skin exposure to a magnetic field might also induce structural alterations that could contribute to an
increase in permeability.
In vitro studies showed a magnetically induced enhancement in benzoic acid
flux, which was observed to increase with the strength of the applied magnetic field.
Other in vitro studies using a magnet attached to transdermal patches containing terbutaline sulphate
(TS), demonstrated an enhancement in permeant flux which was comparable to that attained
when 4% isopropyl myristate was used as a chemical enhancer (53). In the same paper the
effect of magnetophoresis on the permeation of TS was investigated in vivo using guinea pigs.
The preconvulsive time (PCT) of guinea pigs for those subjected to magnetophoretic treatment was
found to last for 36 h which was similar to that observed after application of a patch
containing 4% IPM. This was in contrast to the response elicited by the control (patch without
enhancer), when the increase in PCT was observed for only 12 h. In human subjects, the levels
of TS in the blood was higher but, not significantly different to that observed with the patch
containing 4% IPM. The fact that this technique can only be used with diamagnetic materials will
serve as a limiting factor in its applicability and probably explains the relative lack of interest in
the method.
Magnetophoresis

32. 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

33. Objectives of Rate-Controlling
TDD Systems
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
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.

34. Objectives of Rate-Controlling
TDD Systems
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.

35. Advantages of TDD Systems
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.

36. Advantages of TDD Systems
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)

37. 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.

38. 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.

39. General Considerations
in the use of TDD Systems
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.

40. General Considerations
in the use of TDD Systems
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.

41. 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 6 mg/day. The patches are applied to
scrotal skinwhere optimal absorption occurs. The
patches is worn22 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

42. 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.
Examples: 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
Examples: Transderm-Nitro and Transderm-Scop

43. Examples Of TDD Systems
1. Clonidine -Catapress -TTS
Four-layered patch:(1) backing layer of pigmented
polyester film (2) drug reservoir of clonidine,
mineral oil, polyisobutylene, and colloidal silicon
dioxide, (3) a microporous polypropylene
membrane controlling the rate of drug delivery,
and (4) 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.

44. Examples Of TDD Systems
2. Estradiol -Estraderm
Four layered patch:(1) transparent polyester film,
(2) drug reservoir of estradiol and alcohol gelled
with hydroxypropyl cellulose, (3) an ethylenevinyl
acetate copolymer membrane, and (4) an
adhesive formulation of light mineral and
polyisobutylene.
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.

45. Examples Of TDD Systems
3. Nicotine -Nicotrol
Multi-layered rectangular patch:
(1)outer backing of laminated polyester
film, (2) rate-controlling adhesive,
nonwoven material, and nicotine, (3)
disposable liner removed prior to use -
Aid in smoking cessation programs

46. Examples Of TDD Systems
4. Nitroglycerin -Deponit
Nitroglycerin in a matrix of lactose, plasticizer, polyisobutylene,
and aluminized plastic
Use: to provide controlled release of nitroglycerin continuously
for a 24 hour period.Patches are applied to inner part of upper
arm, shoulders, or chest.
5. Nitroglycerin -Nitro -Dur
Nitroglycerin in a gel like matrix composed of glycerin, water,
lactose, polyvinyl alcohol, povidone and sodium citrate sealed
in a polyester foil polyethylene laminate.
Use: same as # 4

47. Examples Of TDD Systems
6. Scopolamine -Transderm -Scop
Four layered patch: (1) backing layer of
aluminized polyester film, (2) drug reservoir of
scopolamine, mineral oil, and polyisobutylene,
(3) a microporous polypropylene membrane for
rate delivery of scopolamine, and (4) adhesive of
polyisobutylene, mineral oil, and scopolamine
Use: for continuous release of scopolamine
over a 3-dayperiod 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

51. Liner-Protects the patch during storage. The
liner is removed prior to use.
Drug-Drug solution in direct contact with
release liner
Adhesive-Serves to adhere the components
of the patch together along with adhering the
patch to the skin
Membrane -Controls the release of the drug
from the reservoir and multi-layer patches
Backing -Protects the patch from the outer
environment
COMPONENTS

54. 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.

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

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

57. 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.

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

59. It is a contraceptive used by women
to prevent pregnancy

60. 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.

61. 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

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

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

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