18-01-2013, 02:41 PM
Polymers in Transdermal Drug Delivery Systems
[attachment=47517]
INTRODUCTION
The development of transdermal drug delivery systems is
a multidisciplinary activity that encompasses
● fundamental feasibility studies starting from the selection
of a drug molecule to the demonstration of sufficient
drug flux in an ex vivo and/or in vivo model
● the fabrication of a drug delivery system that meets all the
stringent needs that are specific to the drug molecule (physicochemical
and stability factors), the patient (comfort and cosmetic
appeal), the manufacturer (scale-up and manufacturability),
and most important, the economy.
Polymers
Polymers are the backbone of a transdermal drug delivery system.
Systems for transdermal delivery are fabricated as multilayered
polymeric laminates in which a drug reservoir or a
drug–polymer matrix is sandwiched between two polymeric
layers: an outer impervious backing layer that prevents the loss
of drug through the backing surface and an inner polymeric
layer that functions as an adhesive and/or rate-controlling membrane.
Transdermal drug delivery systems are broadly classified
into the following three types (1) (see Figure 1).
Reservoir systems. In this system, the drug reservoir is embedded
between an impervious backing layer and a ratecontrolling
membrane. The drug releases only through the
rate-controlling membrane, which can be microporous or nonporous.
In the drug reservoir compartment, the drug can be
in the form of a solution, suspension, or gel or dispersed in a
solid polymer matrix. On the outer surface of the polymeric
membrane a thin layer of drug-compatible, hypoallergenic
adhesive polymer can be applied.
Matrix systems.
Drug-in-adhesive system. 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 (in the case of hot-melt adhesives)
onto an impervious backing layer. On top of the reservoir, layers
of unmedicated adhesive polymer are applied.
Matrix-dispersion system. The drug is dispersed homogeneously
in a hydrophilic or lipophilic polymer matrix. This drugcontaining
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.
Matrix formers
Polymer selection and design must be considered when striving
to meet the diverse criteria for the fabrication of effective
transdermal delivery systems. The main challenge is in the design
of a polymer matrix, followed by optimization of the drugloaded
matrix not only in terms of release properties, but also
with respect to its adhesion–cohesion balance, physicochemical
properties, and compatibility and stability with other components
of the system as well as with skin (4).
A monolithic solid-state design often is preferred for passive
transdermal delivery systems because of manufacturing considerations
and cosmetic appeal. Although polymeric matrices
are used for rate control, adhesion (e.g., a PSA), or encapsulation
of a drug reservoir in transdermal delivery systems (reviewed
in later sections of this article), discussion in this section
is limited to polymers that have been used in the design of
matrices with or without rate control.
Hydroxypropyl methylcellulose (HPMC).
HPMC, a hydrophilic swellable polymer widely used in oral controlled drug delivery,
also has been explored as a matrix former in the design of
patches of propranolol hydrochloride. HPMC has been shown
to yield clear films because of the adequate solubility of the drug
in the polymer. Matrices of HPMC without rate-controlling
membranes exhibited a burst effect during dissolution testing
because the polymer was hydrated easily and swelled, leading
to the fast release of the drug (9).
Rate-controlling membranes
Reservoir-type transdermal drug delivery systems contain an
inert membrane enclosing an active agent that diffuses through
the membrane at a finite, controllable rate. The release rate–
controlling membrane can be nonporous so that the drug is released
by diffusing directly through the material, or the material
may contain fluid-filled micropores — in which case the
drug may additionally diffuse through the fluid, thus filling the
pores. In the case of nonporous membranes, the rate of passage
of drug molecules depends on the solubility of the drug in the
membrane and the membrane thickness.
Release liner
During storage the patch is covered by
a protective liner that is removed and
discharged immediately before the application
of the patch to the skin. It is
therefore regarded as a part of the primary
packaging material rather than a
part of the dosage form delivering the
active principle (38).However, because
the liner is in intimate contact with the
delivery system, it should comply with
specific requirements regarding the
chemical inertness and permeation to
the drug, penetration enhancer, and
water. In case cross-linking is induced
between the adhesive and the release
liner, the force required to remove the
liner will be unacceptably high (23). 3M,
for example, manufactures release liners
made of fluoro polymers (Scotchpak
1022 and Scotchpak 9742, 3M Drug
Delivery Systems, St. Paul, MN).
[attachment=47517]
INTRODUCTION
The development of transdermal drug delivery systems is
a multidisciplinary activity that encompasses
● fundamental feasibility studies starting from the selection
of a drug molecule to the demonstration of sufficient
drug flux in an ex vivo and/or in vivo model
● the fabrication of a drug delivery system that meets all the
stringent needs that are specific to the drug molecule (physicochemical
and stability factors), the patient (comfort and cosmetic
appeal), the manufacturer (scale-up and manufacturability),
and most important, the economy.
Polymers
Polymers are the backbone of a transdermal drug delivery system.
Systems for transdermal delivery are fabricated as multilayered
polymeric laminates in which a drug reservoir or a
drug–polymer matrix is sandwiched between two polymeric
layers: an outer impervious backing layer that prevents the loss
of drug through the backing surface and an inner polymeric
layer that functions as an adhesive and/or rate-controlling membrane.
Transdermal drug delivery systems are broadly classified
into the following three types (1) (see Figure 1).
Reservoir systems. In this system, the drug reservoir is embedded
between an impervious backing layer and a ratecontrolling
membrane. The drug releases only through the
rate-controlling membrane, which can be microporous or nonporous.
In the drug reservoir compartment, the drug can be
in the form of a solution, suspension, or gel or dispersed in a
solid polymer matrix. On the outer surface of the polymeric
membrane a thin layer of drug-compatible, hypoallergenic
adhesive polymer can be applied.
Matrix systems.
Drug-in-adhesive system. 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 (in the case of hot-melt adhesives)
onto an impervious backing layer. On top of the reservoir, layers
of unmedicated adhesive polymer are applied.
Matrix-dispersion system. The drug is dispersed homogeneously
in a hydrophilic or lipophilic polymer matrix. This drugcontaining
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.
Matrix formers
Polymer selection and design must be considered when striving
to meet the diverse criteria for the fabrication of effective
transdermal delivery systems. The main challenge is in the design
of a polymer matrix, followed by optimization of the drugloaded
matrix not only in terms of release properties, but also
with respect to its adhesion–cohesion balance, physicochemical
properties, and compatibility and stability with other components
of the system as well as with skin (4).
A monolithic solid-state design often is preferred for passive
transdermal delivery systems because of manufacturing considerations
and cosmetic appeal. Although polymeric matrices
are used for rate control, adhesion (e.g., a PSA), or encapsulation
of a drug reservoir in transdermal delivery systems (reviewed
in later sections of this article), discussion in this section
is limited to polymers that have been used in the design of
matrices with or without rate control.
Hydroxypropyl methylcellulose (HPMC).
HPMC, a hydrophilic swellable polymer widely used in oral controlled drug delivery,
also has been explored as a matrix former in the design of
patches of propranolol hydrochloride. HPMC has been shown
to yield clear films because of the adequate solubility of the drug
in the polymer. Matrices of HPMC without rate-controlling
membranes exhibited a burst effect during dissolution testing
because the polymer was hydrated easily and swelled, leading
to the fast release of the drug (9).
Rate-controlling membranes
Reservoir-type transdermal drug delivery systems contain an
inert membrane enclosing an active agent that diffuses through
the membrane at a finite, controllable rate. The release rate–
controlling membrane can be nonporous so that the drug is released
by diffusing directly through the material, or the material
may contain fluid-filled micropores — in which case the
drug may additionally diffuse through the fluid, thus filling the
pores. In the case of nonporous membranes, the rate of passage
of drug molecules depends on the solubility of the drug in the
membrane and the membrane thickness.
Release liner
During storage the patch is covered by
a protective liner that is removed and
discharged immediately before the application
of the patch to the skin. It is
therefore regarded as a part of the primary
packaging material rather than a
part of the dosage form delivering the
active principle (38).However, because
the liner is in intimate contact with the
delivery system, it should comply with
specific requirements regarding the
chemical inertness and permeation to
the drug, penetration enhancer, and
water. In case cross-linking is induced
between the adhesive and the release
liner, the force required to remove the
liner will be unacceptably high (23). 3M,
for example, manufactures release liners
made of fluoro polymers (Scotchpak
1022 and Scotchpak 9742, 3M Drug
Delivery Systems, St. Paul, MN).