Chapter 18
Transdermal Films of Diclophenac Sodium S. C . Mandal, M . Bhattacharyya, S. C. Chattaraj, and S. K. Ghosal
Downloaded by YORK UNIV on October 29, 2012 | http://pubs.acs.org Publication Date: March 5, 1993 | doi: 10.1021/bk-1993-0520.ch018
Division of Pharmaceutics, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700032, India
A matrix-dispersion type Transdermal Drug Delivery System (TDDS) of Diclophenac Sodium (DS) was fabricated, for its controlled delivery, based on the rate - controlling polymers, namely Eudragit RS100 (RS) and RL100 (RL), with an objective of studying the effects of a variety of polymer combinations on the drug - release profile. Effect of coadministration of varying concentrations of permeation promoter (Isopropyl myristate), to overcome the diffusional resistance in course of in vitro release and in vitro skin permeation, was quantitatively evaluated. In-depth in vitro release and in vitro skin permeation studies (using excised pretreated abdominal skin of male albino mice) were conducted with the formulations. Matrix - diffusion type kinetics for the in vitro release study, and zero order kinetics for the skin permeation were obtained over 12 hours and 24 hours span of study, for both the cases respectively, with and without enhancers. A strong therapeutic rationale and some unique advantages over conventional dosage forms prompted the choice of TDDS as a favourable mode of delivery for DS (1-3). The drug (advocated for use in rheumatoid disorders and degenerative joint diseases), possesses a short biological half-life (approx. 2 hrs.), low oral bioavailability (54%) due to extensive first pass metabolism (4,5), gastro-intestinal i r r i tation, and a frequent dosing schedule. The physico-chemical parameters of DS were also suitable for formulation into a TDDS (5). Controlled delivery of DS is deemed to be advantageous in many diseased states, and the TDDS designed in this study aims at achieving a prolonged delivery of DS, based on permeability characters of the polymethylmethacrylate copolymers (Eudragits) (6,7) which are being extensively used for rate-controlled drug delivery of a multitude of drugs (8,9). Eudragits RL100 and RS100 are co-polymers of acrylic and methacrylic acid esters with a low content of quaternary ammonium groups. The molar ratio of the ammonium groups and the remaining 0097-6156/93/0520-0257$06.00/0 © 1993 American Chemical Society
In Polymeric Delivery Systems; El-Nokaly, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.
258
POLYMERIC DELIVERY SYSTEMS
neutral(meth)acrylic for
the
RS
German able and
RL
and
RL100 The
RS100.
was
we
value
of
greater
IPM
(8.5)
can
be
quite
considered
hydrophile
-
that
the
and
of
has
an
near
to
of
for
use
character
salt
as
of
these
form of
the
perme in
RS
films
of
properties
of
of
with
nature,
a 6 value
hydrophilic δ value
of
log
Ρ
^3,
solubility
less
and
than
12
those
are
with
nature.
The
value
skin
(10.5)
and
of
drugs
a
and
Hildebrand
entities,
with
DS,
lipophilic-hydro-
hydrophilic
the
permeation-rate
30% w / w .
intermediate
drug
that
suitable
to
theory
of
the
(IPM)
10
signifies the
slightly
characters
in
1:40
for
TDDS.
myristate
those
and
and
stand
non-sensitizing
in
RL
RS
permeabilities
enhancers with
for
lipophile
permeable present
for
lipophilic
12,
Eudragit
RL and
permeability
range
From
with
than
is
P
