This document provides information on the formulation and evaluation of transdermal delivery systems. It begins with an introduction to transdermal drug delivery systems and their basic components, which include polymers, drug substances, penetration enhancers, and adhesives. It then describes various methods for preparing transdermal patches, such as polymer membrane permeation-controlled systems, adhesive diffusion-controlled systems, and matrix diffusion-controlled systems. The document concludes with a discussion of methods for evaluating transdermal patches, including tests to analyze adhesives, thickness, weight uniformity, and percentage elongation break.
3. Introduction:-
A transdermal patch is defined as medicated adhesive
patch which is placed above the skin to deliver a specific
dose of medication through the skin with a
predetermined rate of release to reach into the
bloodstream.
TDDS also known as “Patches”.
Transdermal medication provides safe, convenient and
pain-free self administration for patients.
This type of dosage forms designed to deliver a
therapeutically effective amount of drug across a
patient’s skin.
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4. FORMULATION OF TDDS
Basic Components ofTDDS:
1) Polymer or polymer matrix:-
• Polymers control the release of the drug from the device.
Polymers used inTDDS should have good stability and compatibility
with the drug and other components of the system.
Examples are:-
Natural polymers:- cellulose derivatives, zein, gelatine, shellac,
waxes, gums, natural rubber etc.
Synthetic polymers:- polyethylene, PVC, poly vinyl acetate,
polyacrylate etc.
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5. 2) Drug substance:-
The selection of drug forTDDS is based on physicochemical
properties of drug.Transdermal drug delivery system is much
suitable for drug having -
Extensive first pass metabolism.
Narrow therapeutic window.
Dose should be less (mg/day) .
Low molecular weight (less than 500 Daltons).
Short half-life which causes non-compliance due to frequent dosing.
The drug should be non-irritating and non-allergic to human skin.
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6. 3) Penetration enhancers:-
These are the substance , which facilitate the transport of drug
molecules across the skin by temporarily altering its permeability.
Chemical enhancers:- They insert themselves directly between the
hydrophobic lipid tails and change lipid packing with cause lipid
fluidity and increase the drug permeation.
Solvents:- e.g- water, alcohol, methyl sulfoxide, propylene glycol etc.
Surfactant:- anionic surfactants- sodium lauryl sulphate,
dicotylsulphosuccinate etc.
nonionic surfactants- pluronic F127, pluronic F68 etc.
• Physical enhancement techniques:-
Ionotophorosis- Deliver the charge molecules across the skin by the
use of small electric current.
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7. Sonophorosis- Drug molecules migration through skin
by ultrasonic energy.
Electroporation-Apply short micro to millisecond electric pluse
approx. 100-1000 v/cm to creates temporary aqueous pore in lipid
layer.
4) Adhesives:- Serves to adhere the patch to the skin for systemic
delivery of drug.
ex- acrylates, polyisobutylene, sillicons etc.
5) Backing layer:-
Backing layer protects patch from outer environment.
Ex: Cellulose derivatives, Polypropylene silicon rubber.
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8. Methods of preparation of TDDS:-
1) Polymer membrane
permeation-controlled
TDDS:-
In this system, the drug reservoir is
embedded between an impervious backing
layer and a rate controlling membrane.
The drug releases only through the rate
controlling membrane, which can be micro
porous or non-porous.
In the drug reservoir compartment, the drug
can be in the form of a solution, suspension,
or gel or dispersed in solid polymer matrix.
On the outer surface of the polymeric
membrane a thin layer of drug-compatible,
hypoallergenic adhesive polymer can be
applied.
Ex. - TransdermNitro (Nitroglycerine),
TransdermScop (Scopolamine).
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9. 2) Adhesive diffusion controlled TDDS:-
The drug reservoir is formed by
dispersing the drug in an adhesive
polymer and then spreading the
medicated polymer adhesive by
solvent casting or by melting the
adhesive onto an impervious
backing layer.
The drug reservoir layer is then
covered by a non-medicated rate
controlling adhesive polymer of
constant thickness to produce an
adhesive diffusion controlling drug
delivery system
Ex. –Isosorbide dinitrate
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10. 3) Matrix diffusion controlled TDDS:-
The drug is dispersed
homogeneously in a hydrophilic
or lipophilic polymer matrix.
This drug containing polymer disk
then is fixed onto an occlusive
base plate in a compartment
fabricated from a drug-
impermeable backing layer .
Instead of applying the adhesive
on the face of the drug reservoir, it
is spread along the circumference
to form a strip of adhesive rim .
Ex. - Nitro Dur (Nitroglycerine)
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11. 4) Microreservoir controlled TDDS:-
The drug reservoir is formed by first
suspending the drug in an aqueous
solution of water-soluble polymer and
then dispersing the solution
homogeneously in a lipophilic polymer
to form thousands of unreachable,
microscopic spheres of drug reservoirs.
The thermodynamically unstable
dispersion is stabilized quickly by
immediately crosslinking the polymer
in situ.
ATransdermal system therapeutic
system thus formed as a medicated
disc positioned at the center and
surrounded by an adhesive rim.
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12. Evaluation Methods:-
1) Evaluation of Adhesives:-
Tack properties: It is the ability of the polymer to
adhere to substrate with little contact pressure.
Tack is dependent on molecular weight and
composition of polymer as well as on the use of
tackifying resins in polymer.
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13. Peel Adhesion test:
In this test, the force required to remove an
adhesive coating form a test substrate is
referred to as peel adhesion.
Molecular weight of adhesive polymer, the
type and amount of additives are the
variables that determined the peel adhesion
properties.
A single tape is applied to a stainless steel
plate or a backing membrane of choice and
then tape is pulled from the substrate at a
180°C angle, and the force required for tape
removed is measured.
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14. Rolling ball tack test :-
This test measures the softness of a
polymer that relates to talk.
In this test, stainless steel ball of 7/16
inches in diameter is released on an
inclined track so that it rolls down and
comes into contact with horizontal,
upward facing adhesive.
The distance the ball travels along the
adhesive provides the measurement of
tack, which is expressed in inch.
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15. Quick stick (peel-tack) test:-
In this test, the tape is pulled away from the substrate at 90ºC at a
speed of 12 inches/min.The peel force required breaking the bond
between adhesive and substrate is measured and recorded as tack
value, which is expressed in ounces or grams per inch width.
Thumb tack test: It is a qualitative test applied for tack
property determination of adhesive.The thumb is simply pressed on
the adhesive and the relative tack property is detected.
ProbeTack test: In this test, the tip of a clean probe with a
defined surface roughness is brought into contact with adhesive,
and when a bond is formed between probe and adhesive.The
subsequent removal of the probe mechanically breaks it .The force
required to pull the probe away from the adhesive at fixed rate is
recorded as tack and it is expressed in gram.
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16. Shear strength properties:-
In this particular test, adhesive-coated tape is applied onto a
stainless steel plate.A specified weight is hung from the tape. Shear
strength is determined by measuring the time its take to pull the
tape off the plate parallel.The longer the time taken for removal,
greater is the shear strength.
Physicochemical Evaluation:-
Thickness of the patch :The thickness of the drug prepared
patch is measured by using a digital micrometer at different point of
patch and determines the average thickness and standard deviation
for the same to ensure the thickness of the prepared patch.
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17. Folding endurance:
A specific area of strip is cut and repeatedly folded at the same place
till it broke.The number of times the film could be folded without
breaking gave the value of folding endurance.
Weight uniformity: The prepared patches are to be dried at
60°c for 4hrs before testing. A specified area of patch is to be cut in
different parts of the patch and weigh in digital balance.The average
weight and standard deviation values are to be calculated from the
individual weights.
Percentage elongation break test:
The percentage elongation break is to be determined by noting the
length just before the break point.
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18. References
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glibenclamide, Journal of drug delivery and therapeutics. 2018; 8(5-s):366-371
Hiremath SP, Jujjuri J, Design and evaluation of transdermal patches of timolol maleate
Bentham science publisher. 2017; (6):2141-2150.
Ganju E, Ganju K. Formulation and evaluation of transdermal patch acetohexamide.
Ejpmr, 2016; 3(7), 233-235.
Saleem M.N, Idris M. formulation design and development of a Unani transdermal
patch for antiemetic therapy and its pharmaceutical evaluation. Hindawi publishing
corporation scientifica.2016;(5):169-180.
Tanwar H, Sachdeva R. A review on transdermal drug delivery system, International
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