April Journal-2009.p65 - Association of Biotechnology and Pharmacy

Current Trends in Biotechnology and Pharmacy
Vol. 3 (2) 188-196, April 2009. ISSN 0973-8916
indicating 100% flatness. It shows that no amount
of constriction in the patches and thus they could
maintain a smooth surface when applied onto the
skin. The folding endurance was found to be
between 209 ± 5.34 to 249 ± 1.00 and it was
found to be satisfactory.
In vitro release studies
The results of in vitro drug release studies
from transdermal patches are depicted in Fig 2
and 3. The cumulative percent of drug release
from formulations of A-series was 70.70, 91.60,
95.52 and 94.4 respectively from A-1, A-2, A-3
and A-4 and of B-series was 58.02, 63.24, 85.07
and 89.55 respectively from B-1, B-2, B-3 and
B-4 (Table 3). The drug release from different
formulations was increased in the following order:
A-3>A-4>A-2>B-4>B-3>A-1>B-2>B-1.
Variable release profiles of A-HCl from
different experimental patches composed of
various blends of ERL/HPMC and ERS/HPMC
were observed. The process of drug release in
most controlled release devices is governed by
diffusion, and the polymer matrix has a strong
influence on the diffusivity as the motion of a small
molecule is restricted by the three-dimensional
network of polymer chains (24).
Release rates were increased when the
concentration of HPMC increased in the
formulations. This is because as the proportion
of this polymer in the matrix increased, there was
an increase in the amount of water uptake and
hydration of the polymeric matrix and thus more
drug was released (25). Formulation A4 showed
less drug release compared to formulation A3,
this is because the high proportion of HPMC
swellable polymer further increases the tartuosity
and diffusional path length, resulted in decreased
drug release. However the difference was
statistically insignifinacant (p>0.05).
The data was fitted to different kinetic
models to explain drug release mechanism. The
193
results suggested that the drug release followed
Higuchi model as it was evidenced from correlation
coefficients and indicating that the drug release
was taking place by the process of diffusion. The
correlation coefficients (0.87 to 0.97 in A4 and
A1; 0.86 to 0.98 in B4 to B1) were greater than
the correlation coefficients of zero order (0.67 to
0.65 in A4 and A1; 0.68 to 0.88 in B4 to B1) and
first order kinetics (0.56 to 0.71 in A4 to A1, 0.57
to 0.72 in B4 to B1). As the concentration of
HPMC increases in the formulations
Ex vivo skin permeation studies
The results of ex vivo permeation of A-
HCl from patches are shown in Fig 4 and 5. The
cumulative percent of drug permeation from
formulations of A-series was 61.94, 75.55, 84.89
and 80.97 respectively from A-1, A-2, A-3 and
A-4 and of B-series was 44.4, 45.7, 62.31 and
71.45 respectively from B-1, B-2, B-3 and B-4
(Table 3). The order of drug permeation from
different formulations was increased in the
following order: A-3>A-4>A-2>B-4>B-3>A-
1>B-2>B-1
Formulations A-3 (84.89 %) and B-4
(71.45 %) showed maximum drug permeation in
their respective series with permeability
coefficients of 3.43 X10 -2 cm h -1 and 3.02 X 10 -2
cm h -1 (Table 3). The skin permeation profiles of
the test formulations were in conformity to the in
vitro drug release pattern. The cumulative amount
of drug permeated as well as the permeability
coefficient (Kp) for TDDS were in the order of
A-3>A-4>A-2>A-1 and B-4>B-3>B-2>B-1 for
the A and B series, respectively. The results
corroborated that higher the drug release from
the formulation, higher was the rate and extent of
drug permeation. Again the Kp for formulation
A-3 was high than B-4 leading to conclusion that
ERL 100 and HPMC combination is better than
ERS 100 and HPMC as the polymeric precursor
for the A-HCl transdermal formulation. As the
concentration of hydrophilic polymer was
Mamatha et al